2016

Introduction

In the UK, all newly graduated doctors spend their first two years of work rotating between different specialities, usually spending four months in each placement, before applying for speciality training. This period is called the Foundation Programme.

In January 2016, the Royal College of Psychiatrists published its first ever strategy on Broadening the Foundation Programme to address the need to improve the psychiatric training experience for foundation doctors. The strategy’s aim is to “ensure the delivery of a high-quality training experience in all psychiatry foundation placements”.¹

Over the last few years, the number of Foundation training posts in psychiatry in England and Wales has significantly increased. Health Education England aims that all Foundation doctors should rotate through a community or an integrated placement (psychiatry is considered as a community placement) from August 2017.²

As such, the College highlights the need to provide a supervised and well-structured psychiatric training experience for Foundation doctors. This aims not only to improve recruitment into psychiatry but also to ensure doctors have a good working knowledge and understanding of psychiatry and psychiatric services, no matter what career they pursue.

Mentoring provides an additional support and therefore can be helpful to improve the placement of Foundation doctors in psychiatry.

We implemented an ambitious mentoring scheme in Norfolk and Suffolk NHS Foundation Trust (the seventh largest mental health trust in the UK). The paper describes its essential component together with a brief review of the literature on mentoring in clinical settings, focusing on Foundation placements.

Why is mentoring is needed for Foundation doctors in psychiatry?

The literature on mentoring for medical professionals draws attention to the idea that it is beneficial to all doctors at all stages of their career to experience mentoring in some form or another. However, mentoring is of particular importance to doctors moving to a new job or organisation ³, thus making it highly relevant to Foundation trainees.

For newcomers, most of the mentoring support will focus on helping them settle into their new role, becoming familiar with, and developing an understanding of the expectations of their employers.⁴

Evidence shows that the quality of care in any organisation can be improved when clinical leaders support time for activities such as reflection, coaching and mentoring ⁵.

Most Foundation doctors will lack experience in psychiatry and will need a substantial amount of guidance from their supervisors and their teams.⁶ Research has shown that the transition from student to doctor is a difficult one and can be associated with significant levels of emotional stress.⁷

Foundation doctors find psychiatric assessments physically and emotionally challenging. They feel they lack the specialist knowledge and skills to deal with complex patients, especially concerning self-harm, personality and eating disorders. Dealing with such complex diagnostic categories requires knowledge, skill, understanding as well as physical and emotional robustness. Due to the relative lack of focus on such topics in most undergraduate medical training, a comprehensive support in psychiatric placements is essential.

Psychiatry is very different from other specialities in the way services are configured and delivered: junior doctors may face isolation as psychiatric units are typically spread across a wide geographical area and often lack a centralised meeting place for junior doctors (e.g. a doctors’ mess). In addition, they may find themselves the lone practitioner when on call, which can be daunting for many.

Clinical and Educational supervision is provided to Foundation doctors in similar ways to other rotations. However, the consultants delivering this essential support often focus only on clinical issues related to knowledge and skills. Furthermore, it is easy to see that the best guides to new trainees regarding the idiosyncrasies of the speciality and its services are likely to be trainees who have spent some time in those services and are more able to detect the specific stresses new doctors may experience and may find difficult to articulate.

Furthermore, mentoring fosters a productive peer-to-peer relationship. The learning needs of the Foundation doctor can be considered alongside their personal and professional interests and lifestyle. Questions can be posed in a non-judgmental forum, without fear of being ridiculed or condemned. The fundamentals of on-call systems, clinical cases and management options can all be considered at a level appropriate to their junior grade. Tips for examination success and information about essential courses and core texts can be shared. Job choices and research opportunities can be discussed. Day to day difficulties and mismatches between expectation and reality can be identified and possibly overcome. Where this is not possible next steps can be identified, and clinical and educational supervisors can be drawn in for higher level support. The benefits of the scheme are broad.

Finally, although mentoring is different from role-modelling (teaching by example and learning by imitation), it has been shown toserve some of the same aims of role-modelling, including enhancing problem-solving abilities of the mentee, improving professional attitudes, showing responsibility and integrity, and supporting career development. ⁸

What is mentoring?

Mentoring can mean different things to different people. There are various definitions which can create confusion between mentoring and other formal structures of support such as supervision, coaching, consultation, befriending or friend systems and even counselling. However, mentoring is none of the above but at the same time a combination of them.

The Standing Committee on Postgraduate Medical and Dental Education (UK) defined mentoring as ‘The process whereby an experienced, highly regarded, empathetic individual (the mentor) guides another individual (the mentee) in the development and re-examination of their ideas, learning, and personal and professional development”.⁹

The term “mentoring” takes us back to Greek mythology: Mentor was a person: he was the friend of Odysseus who was asked to look after Odysseus’ son Telemachus when Odysseus was fighting in the Trojan Wars. The name Mentor was later used to describe a trusted person, a supporter, or a counsellor.¹⁰

Mentoring as a professional developmental tool became popular in the private sector organisations in the USA during the 1970s and was introduced to the area of health during the 1990s ¹¹. Since then, it has been widely used in various organisations.

Aims of mentoring

Mentoring has the advantage of being a flexible supporting tool, unlike other structured processes (e.g., clinical supervision or coaching) where the goals are set clearly from the start of the relationship between the supervisor and supervisee. The aims of mentorship are summarised in Table 1.

Types of mentoring

Buddeberg-Fischer and Herta ¹¹ discussed various types of mentoring based on the numbers of mentors and mentees and their professional status or grade:

1. One to one mentoring (between a mentor and a mentee).
2. Group mentoring (one mentor and a small group of mentees)
3. Multiple-mentor experience model (more than one mentor assigned to a group of mentees).
4. Peer-mentoring (the mentor and mentee are equal in experience and grade): This mentoring is used mainly for personal development and improving interpersonal relationships. Mentor and mentee roles can be reversed. Also, called ‘co-mentoring’.

Distance or e-mentoring is becoming more popular, and it has the advantages of being “fast, focused, and typically centred on developmental needs”. ¹²

Structured vs. flexible mentoring

Evidence suggests that providing mentorship through a rigid and structured process can be counterproductive. ¹³ Mentors and mentees usually work in different locations, making it difficult for both to have a set of pre-planned meetings and topics for discussions.

Another advantage of the flexibility of mentoring is that it does not follow a “tick box” exercise but encourages informal discussions and exploration of whatever comes to mind during meetings. Doubtless, having some structure to the overall mentoring process is important as it ensures that the mentoring session doesn’t become an informal befriending or friend support system. Table 2 sets out the main benefits of mentoring.

Table 2-Benefits of mentoring. Developed from Mentoring – Chartered Institute of Personnel and Development (CIPD) Factsheet. Revised February 2009 ¹⁴. Available from: https://www.shef.ac.uk/polopoly_fs/1.110468!/file/cipd_mentoring_factsheet.pdf

Are there any Disadvantages of mentoring?

There is extensive literature on the benefits of mentoring, but is there any harm associated with it?

As with any intervention, it does carry some potentially adverse effects. Mentoring can be perceived to “infantilise” junior employees rather than empowering them ¹⁰. This perception is probably more common among employees who see themselves as senior or very competent and think of themselves as able to adapt to change very quickly.

Mentoring might hinder creativity in new employees and inhibit them from thinking “outside the box” as it might re-enforce the message that ‘this is how we do things here’. ¹⁰

Clashes of personalities or other interpersonal factors could lead to a troubled mentor-mentee relationship and cause distress to both parties. Hence, plans must be put in place in any formal mentoring scheme to ensure an amicable ending to this relationship. Multiple mentor allocation mentioned earlier could also prevent such interpersonal problems and help to tackle them early on.

Furthermore, some mentees may feel uncomfortable with the influence or authority of the mentor, and this may hinder the progress of the mentoring relationship. ¹³ This is particularly relevant when the mentor is also involved in the formal assessment of the performance of the mentee (e.g. being the line manager or supervisor) or when a mentee who lacks self-confidence is paired with an overconfident mentor.

Good mentors avoid common pitfalls in the mentoring process, such as a patronising attitude, breaches of confidentiality and offering direct advice to the mentees. Instead, they encourage the mentee to reflect and come up with their answers. ¹⁵

Finally, mentoring can be perceived as an additional demand on doctors during their training, and some may feel that they are forced to provide it or receive it during placement. However, it must be remembered that mentoring should always be voluntary and flexible to meet the individual’s needs and not an additional ‘box to tick’ or a portfolio enrichment exercise.

The Mentoring Scheme for Foundation Doctors in Psychiatry Norfolk:

The scheme started in December 2015 and initially ran as a pilot in Norfolk with the support of all stakeholders. The mentoring scheme coordinator (YH) contacted twelve Foundation doctors by email, welcoming them to the Trust and inviting them to participate. The welcome email contained information about mentoring, including the benefits it may offer.

The voluntary nature of this scheme was highlighted so that the doctors didn’t feel they were being pressured to be enrolled.

Of the 12 doctors invited, five took up this opportunity. Uptake has remained constant over the consequent cohorts of Foundation doctors for many reasons. Those deciding not to enrol in this scheme explained that they felt happy with the support provided by their clinical supervisors. However, some doctors asked for a mentor halfway through their placement when they felt that they needed additional support. In these instances, a mentor was allocated to them as soon as possible.

Mentors were core and higher trainees already involved in supporting more junior psychiatric trainees through informal mentoring. Their experience meant there was no need for formal training. However, reading material was circulated to them to highlight the roles and responsibilities of mentors and what to do if any problem arose during mentoring. Monthly mentors’ meetings were very helpful to discuss issues arising in mentoring and offer peer to peer support.

Also, there were regular meetings and discussions between the mentoring coordinator, the Director of Medical Education, and Medical Director of the Trust to resolve any issues facing the Foundation doctors and provide feedback to improve the Psychiatric placement.

During the first meeting, the mentors and mentees agreed on the aims of mentoring drawing up a list of objectives that the Foundation doctor would like to achieve by the end of the placement. Following this initial meeting, there should have been once monthly face to face meetings throughout the placement. The mentor and mentee agreed on the most convenient means of communication (e.g. using text messages, emails, etc.) outside scheduled meetings.

All mentors kept a record of the mentoring meetings, with the mentoring coordinator informed about these meetings. Issues discussed were confidential and not shared with the coordinator or supervisors unless the mentee gave specific consent.

At the end of the mentoring scheme, the coordinator collected feedback from mentees and mentors using a structured questionnaire that was designed by the coordinator using SurveyMonkey® website. The feedback highlighted the positive aspects of mentoring as well as areas for improvement.

End of mentoring survey

Mentors reported that acting as a mentor without being involved in clinical supervision allowed them to offer objective advice and support in a way that would have been harder if they were directly involved in the workplace. One Foundation doctor experienced bullying from another member of the team who was a locum doctor. The mentor supported the Foundation doctor, and the issue was addressed and resolved promptly. There was a significant risk that they would have been left isolated and unsupported during this time if the mentor scheme had not been in place.

The topics discussed were varied, and this suggested that mentoring was not limited to a aspect of the job (see Table 3)

Mentees reported that they found mentoring useful and supportive of learning and development. This was especially important in a speciality that they had little experience of as an undergraduate. With a mentor in Psychiatry, the Foundation doctors reported that they could identify areas of development, including leadership and teaching opportunities for Foundation doctors.

Overall, mentoring was shown to be a useful tool to improving Foundation doctors’ experience in Psychiatry by offering extra support during placement in a challenging medical speciality.

Table 4 summarises the areas of development suggested by the mentors and mentees.

Limitations

Feedback from mentors and mentees showed an overall satisfaction with the scheme, but it was not possible to measure such satisfaction quantitatively, this was expected from an approach which is willfully kept outside the realm of performance management.

According to the literature on mentoring, most mentoring schemes lack a clear structure, as well as a clear evaluation process of its short and long terms, benefits ¹¹.In our scheme, we addressed this by continually monitoring the mentoring process and collecting feedback from mentees and mentors. Another limitation involves training the mentor himself and finding the time in a highly pressurised and heavy workload environment.

There are many questions that the literature on mentoring is yet to answer. For example, what are the long-term benefits of mentoring? Would our Foundation doctors who received mentoring be more successful professionally and personally compared to their peers who decided not to participate? These questions remain unanswered as our pilot was not set up to address this general shortcoming of current knowledge and understanding.

Conclusions and recommendations

Mentoring provides a focused opportunity to target the wider needs of the trainee. Not only could this encourage Foundation doctors to pursue a career in Psychiatry, but it also provides the space for them to learn how to incorporate psychiatric skills into whatever speciality they choose to pursue.

As a new doctor in a novel environment, being expected, welcomed, and gently guided into the job is invaluable. With the hindsight of our training experiences (good and bad), junior doctors are ideally placed to support more junior colleagues at all levels.

There is a need to develop links with other mentoring schemes to exchange experiences and learn lessons from others. Research has shown the importance of supporting mentors in their roles through regular meetings where mentors learn from each other. ¹³

In our experience, the mentoring scheme worked both alongside and separately to clinical and educational supervision and the opportunity for reflective practice offered in Balint groups. Mentoring added another level of support for the Foundation doctors, which was deemed beneficial by those participating.

We recommend more research is required to determine whether mentoring will increase recruitment to psychiatry. Organisations responsible for the training of doctors should support formal mentoring schemes and supervisors should ensure that mentors and mentees have protected time in their timetable due to the benefits of the mentoring experience to the doctors and the employing organisations.

Finally, funding should be available to support training of mentors in their workplace and aim to develop their skills in helping their mentees. Many private organisations offer mentoring training packages (including classroom and online training) for competitive prices. These courses provide useful resources to mentors and may help to increase the motivation of mentors to continue their participations in mentoring.

Appendix:

How does mentoring work? A simple three stage model:

Figure 1- The three stage model of mentoring. Developed from Alred et al (1998). Alred, G., Gravey, B. and Smith, R, 1998, Mentoring pocketbook. Alresford: Management Pocketbooks.

One of the unique characteristics of mentoring is that it is a partnership between two individuals (mentor and mentee) where both contribute to its growth and sustainability. It is based on trust, eagerness to learn and mutual respect. ¹⁶

Alred et al (1998) ⁴ described a model of mentorship with three stages: exploration, developing new understanding and then action planning (Figure 1). Both the mentors and mentee have certain roles and responsibilities in each stage and it is only through their collaborative work that the benefits of mentoring can be obtained.

The stage of exploration is characterised by the building of a relationship between the mentor and the mentee. Trust, confidence and rapport start to develop and hopefully grow throughout the mentoring process. Methods such as active listening, asking open questions, and negotiating an agenda are essential to facilitate this growth.

The second stage is where new understanding develops, is characterised by showing support to the mentee, demonstrating skills in giving constructive feedback and challenging negative and unhelpful cognitions.

Key methods employed in this stage include recognition of the strengths and weaknesses of the mentee, giving them information, sharing experience and establishing priorities for the mentee to work on.

In the third and last stage of the mentoring, action planning, the mentee takes the lead in negotiating and agreeing on the action plan, examining their options and developing more independent thinking and decision-making abilities.

A good mentor should help the mentee to gain confidence and knowledge over time. In order to achieve this, the mentor helps the mentee to develop new ways of thinking and improve their problem-solving abilities.

Monitoring the progress and evaluating the outcomes of the mentoring process is essential to ensure that the mentoring relationship is going in the right direction.

Acknowledgement

We would like to thank Dr Stephen Jones (Consultant CAMHS and former Training Programme Director), Dr Trevor Broughton (Consultant Forensic Psychiatrist, Director of Medical Education), Dr Bohdan Solomka (Medical Director) from Norfolk and Suffolk NHS Foundation Trust for their unlimited support for the mentoring scheme.

We also would like to thank Dr Calum Ross (Foundation Training Programme Director-FY1) and Mr Am Rai (Foundation Training Programme Director -FY2), Norfolk and Norwich University Hospital for their support in implementing this scheme. Dr Srinaveen Abkari (Specialist Registrar, Norfolk, and Suffolk NHS Foundation Trust) is one of our mentors who also contributed useful ideas to the development of this paper.

Finally, we would like to thanks all our mentors who provided the support for the Foundation, without their efforts, this scheme would not have succeeded.

Introduction

Metastatic bone disease is a relatively common event in the advanced stages of many malignancies.¹ Bone-modifying agents decrease the incidence of skeletal-related events (SREs) such as spinal cord compression and bone fracture, as well as the need for skeletal radiotherapy or surgery.²

Bone modifying agents such as intravenous bisphosphonates (IV BPs) (e.g. pamidronate and zoledronic acid) and denosumab are approved for prevention of SREs. IV BPs are primarily used and effective in the treatment and management of cancer related conditions such as multiple myeloma (MM), and breast cancer with skeletal metastases, because they reduce bone pain, hypercalcemia, and the risk of pathologic fractures.³

Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor, represents a breakthrough in the treatment of osteoporosis, MM, and bone metastases. The Food and Drug Administration (FDA) approved it in 2010 for the prevention of SREs in patients with bone metastases and in 2011 for the prevention of endocrine-therapy induced bone loss in patients taking aromatase inhibitors for breast cancer and in patients with non-metastatic prostate cancer.

Three international, randomised, double-blind, double-dummy phase III studies have evaluated denosumab versus zoledronic acid for the treatment of SREs in breast and prostate cancers, and in combined solid tumours and MM. Denosumab’s superior efficacy over zoledronic acid was demonstrated in the studies of patients with advanced breast or prostate cancer, as well as in a pre-specified integrated analysis of all patients enrolled across the three studies.⁴

In the 2014 position paper of the American Association of Oral and Maxillofacial Surgeons (AAOMS), the nomenclature “bisphosphonate-related osteonecrosis of the jaw” changed to “medication related osteonecrosis of the jaw” (MRONJ). MRONJ is defined as cases in which all of the following 3 characteristics are present⁵:

• current or previous treatment with antiresorptive or antiangiogenic agents
• exposed bone or bone that can be probed through an intraoral or extra-oral fistula in the maxillofacial region that has persisted for longer than 8 weeks
• no history of radiation therapy to the jaws or obvious metastatic disease to the jaws

Other terminologies used previously include “denosumab related osteonecrosis of the jaw” (DRONJ), and “antiresorptive agent-induced ONJ” (ARONJ).

The aetiopathogenesis of MRONJ related to denosumab therapy remains enigmatic, and hypotheses have focused on reduced bony turnover, infection, toxicity of the soft tissue, and antiangiogenesis. The epidemiology also remains unclear, and reported incidence varies widely.⁶ Overall, it is estimated that bone necrosis can develop in about 0.7-1.9% of patients with malignancy who are given high-potency IV BPs (such as zoledronic acid), and in 0.01–0.1% of those with osteoporosis who take low-potency oral BPs (such as alendronate). Data relevant to denosumab given subcutaneously in patients with metastatic cancer and osteoporosis seem to replicate those when IV high-potency BPs are administered.⁷ The risk of osteonecrosis of the jaw (ONJ) is higher in patients exposed to concomitant antiagiogenic medication. The individuals’ risk of ONJ is further determined by factors such as the potency of agent, cumulative dosage or duration of antiresorptive treatment, route of administration, comorbidities and local factors such as periodontal disease.^8,9 Oral hygiene plays a significant role with evidence supporting a strong correlation between bacteria associated with periodontal disease and MRONJ.¹⁰

MRONJ typically manifests as painful and often infected areas of necrotic bone, which subsequently may lead to severe chronic pain and facial disfigurement. This adversely affects the ability to eat, speak and lowers the quality of life. Adverse events related to RANKL inhibitors are usually considered to be infrequent and low in occurrence. Unfortunately from our recent clinical experience at Sheffield Teaching Hospitals' Trust, there have been several new cases presented in a very short period of time. In this paper we present a case series of MRONJ related to denosumab therapy since adverse events of denosumab in the mandible or maxilla have received relatively little attention.

The aim of this article is to highlight the elevated risk of MRONJ in patients receiving denosumab treatment and educate all health care providers involved in the management of such patients. Furthermore, the mechanisms of denosumab, comparison with bisphosphonates and the reported management strategies are reviewed.

Mechanism of Denosumab

Denosumab is an antiresorptive agent that exists as a human IgG2 monoclonal antibody and inhibits the binding of the receptor activator of nuclear factor kappa-B ligand (RANKL) to RANK (Receptor Activator of Nuclear Factor kappa-B). The binding normally signals the proliferation of osteoclasts, as RANK is expressed on the surface of osteoclasts and their precursors, whereas its ligand, RANKL, is a membrane bound protein expressed by bone marrow stromal cells, osteoblasts and T-lymphocytes. The activation of RANK is integral to the function of osteoclasts. Osteoprotegerin binds to membrane bound RANKL on osteoblast which in turns decreases the osteoclastic activity and in theory negatively effects bone turnover. Denosumab acts similarly to osteoprotegerin but has a higher affinity for RANKL.^11-13

Denosumab follows nonlinear, dose-dependent pharmacokinetics. The bioavailability of one subcutaneous denosumab injection is 61% and serum concentrations are detected within 1 hour. Maximum serum concentrations occur in 5-21 days and cessation of osteoclast activity occurs within six hours of the subcutaneous injection. The normal function is restored approximately six to nine months later, whilst bone turnover returns to normal shortly after this.¹⁴ Based upon monoclonal antibody pharmacokinetics, denosumab is most likely cleared by the reticuloendothelial system with minimal renal filtration and excretion thus avoiding nephrotoxicity. Its elimination half-life is 32 days, and it does not incorporate into bone.¹⁵

It is currently marketed as Prolia® and Xgeva®, approved by FDA. Prolia® is administered subcutaneously every six months and has shown to reduce the incidence of new vertebral, non-vertebral, and hip fractures in osteoporotic patients.^16,17 Xgeva® is also effective in reducing SRE related to metastatic bone disease from solid tumours when administered intravenously on a monthly basis.^17,18

RANKL Inhibitors and BPs Pharmacokinetics

There are fundamental differences between denosumab and BPs with regard to their mode of action. Denosumab is an antibody and acts extracellularly whereas BPs act intracellularly. As such, BPs must be present in the circulation and available for reuptake into bone for prolonged periods to function.¹⁹ There is not any evidence of drug recycling with RANKL inhibitors, and therefore it is suggested that their adverse effects can be reversible with discontinuation, in fact leading to a transient rebound phenomenon, which can be restored, with subsequent treatment.^14,20 On the other hand, recycling of BPs in the circulation system has been proposed as a reason for the long duration of action even after cessation which can be up to 12 years.

The US FDA-approved manufacturer’s package insert for both zolendronate and pamidronate states that “there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ in patients who require dental procedures during therapy and that clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/ risk assessment”. The package insert for denosumab does not address the issue of treatment continuation in patients who develop MRONJ to date.

Denosumab is a circulating protein capable of distributing throughout extravascular space. It is expected to reach all sites within bone including intracortical sites unlike with BPs. BPs have strong affinity for hydroxyapatite and bone mineral which limits their even distribution throughout the skeleton, particularly to sites deep within the bone.^19,21 This can explain the more profound inhibition of bone remodelling with denosumab than that seen with BPs.

Case Series

Case 1

A 55 year-old lady referred to a dedicated Oral Surgery nerve injury clinic for an opinion and management of her left sided inferior alveolar nerve (IAN) paraesthesia. The patient presented with a history of numbness in the left sided inferior alveolar nerve distribution following removal of the left mandibular second premolar (LL5) in July 2014. She was asymptomatic until she had the LL5 removed and since had suffered with constant pain and numbness. A year later, she had removal of the left mandibular first molar (LL6) and gave a history of recurrent infections and excruciating pain in her mandible over the past two months. On presentation she had an obvious submental swelling and left sided IAN anaesthesia.

Medically she was diagnosed with breast cancer in 2011, for which she underwent wide local excision followed by chemotherapy. She then was placed on unknown clinical trial that we identified at the time to be denosumab trial, following liaison with the Oncology team. She is currently receiving intravenous denosumab every three months.

Clinical examination revealed a grossly mobile anterior mandible with widespread bony necrosis and associated osteomyelitis. Sensory testing revealed complete anaesthesia in the left sided IAN distribution secondary to MRONJ.

An OPG (Orthopantogram) and CBCT (Cone-Beam Computerised Tomography) revealed an extensive patchy area of ill-defined bone loss in the anterior mandible extending posteriorly to the premolar/molar areas bilaterally (Fig 1).

Figure 1 A) OPG showing non-healing sockets in the left mandible with extensive bony destruction together with periosteal reaction extending to the right mandible as shown by the arrows.

Rather interestingly, the bony destruction was evident bilaterally with the patient only having had extraction of teeth in the left mandible (Fig 1). This could be the case of spontaneous ONJ in the right mandible or an extensive ONJ arising from simple extractions on the left side.

Figure 2 3D reconstruction of the CBCT image demonstrating extensive bony destruction involving the lower border of anterior mandible in keeping with a spreading chronic bony infection and clinical presentation of submental swelling as showing by arrows.

Case 2

A 66-year-old female referred by her general medical practitioner (GMP) with a 3-month history of delayed healing following a tooth extraction in the left posterior mandible. She had moderate to severe discomfort and reported multiple previous infections and purulent discharge from the area, which treated with multiple courses of antibiotics. In addition, she reported discomfort from the root treated right mandibular first and second premolar teeth (LR4 and LR5).

Medically she was diagnosed with breast cancer over 10 years ago for which she underwent resection followed by chemotherapy. Three years ago, she diagnosed with metastatic deposits and therefore has been receiving intravenous denosumab every six weeks since then. Other medications include steroids, chemotherapy agents, antihypertensives and analgesics. She did not receive any radiotherapy or BPs treatment in the past.

Clinical presentation revealed a heavily restored dentition with chronic generalised periodontal disease. There was evidence of widespread bone loss clinically and radiographically. The slow healing socket in the left mandible was visible but did not have any exposed bone (Fig 3). The lower right first and second premolar teeth (LR4 and LR5) were clinically and radiographically sound.

Figure 3. Non-healing socket in the left posterior mandible with no evidence of exposed bone or suppuration as showing by white arrow. Gingiva recession (black arrows) is evident in the LL6 and LL5 teeth in keeping with chronic periodontal disease.

Figure 4 Coronal sections of CBCT A and B showing multiple lytic areas within the inferior cortex of the mandible and incomplete healing of the extraction sockets.

On follow-up appointments, the patient suffered multiple repeated infections in the right and left posterior mandible and due to deteriorating periodontal disease, the LR4, LR5, LR6 were extracted by her own general dental practitioner (GDP) due to severe mobility. All three extraction sockets failed to heal (Fig 5) leading to an extensive area of exposed bone in the right mandible, extending from the lower right first premolar (LR4) to lower left first molar (LL6) region. Conservative management was embarked which included antibiotics, chlorhexidine mouthwash and routine oral hygiene appointments. Selective sharp bone trimming and three sequestrectomies were undertaken. At the same time, liaison with the patient’s oncologist resulted in cessation of the denosumab therapy and complete resolution of her oral symptoms.

Figure 5 Clinical picture of exposed necrotic bone (white arrows) following simple extractions of periodontally involved teeth.

Case 3

A 76-year-old lady referred to the Oral Surgery department by her GDP with a 3-month history of a non-healing lower left first premolar (LL4) socket. The patient was treated with two courses of antibiotics prior to referral which provided only temporary relief to her symptoms.

Medically she was diagnosed with breast cancer 10 years ago and recently commenced intravenous denosumab for metastatic disease. She also receives hormone therapy and palliative radiotherapy to the spine.

On clinical examination, there was a partially healed LL4 socket with a rather granulomatous appearance. There was no clinical evidence of suppuration or bony exposure. Radiographs confirmed the absence of bony infill in the socket. Local debridement and biopsy of the granulomatous tissue was performed to exclude any metastatic disease. Biopsy report confirmed the presence of inflammation tissue.

Figure 6 CBCT scan; A and B sagittal views, C axial view and D 3D reconstruction. Extensive periosteal reaction extending from the midline of the mandible to the left molar region is evident in keeping with chronic osteomyelitis secondary to MRONJ.

Liaison with the microbiologist suggested a long-term antibiotic course to arrest osteomyelitis. Further liaison with the oncology team, resulted in denosumab being stopped for 4 months. On subsequent review appointments, patient’s symptoms improved however, there is now an area of exposed bone in the LL4 region as shown in Fig 7.

Figure 7 Clinical photo illustrating exposed bone (white arrow) in the LL4 region without evidence of local infection.

Case 4

A 65-year-old lady referred to the Oral Surgery department by her GDP with a history of a sore upper mouth and jaw underneath the dentures which is unable to wear.

Medically she was diagnosed with disseminated breast malignancy including bone metastases 3 years ago and for that, she is on exemestane and IV Denosumab monthly.

Clinical examination revealed multiple draining sinuses in the anterior maxilla. There was a partially healed LL4 socket with a rather granulomatous appearance and tenderness on palpation. There was neither discharge from the area nor any exposed bone. Radiographs confirmed the absence of bony infill in the LL4 socket. Local debridement and biopsy of the granulomatous tissue was performed to exclude any potential malignancy and it was confirmed as inflammation tissue.

Figure 8 CBCT scan; A axial view, B and C 3D reconstruction. A 25mm fragment of right anterior maxilla is beginning to sequestrate. This extends from the anterior margin of the right maxillary sinus approximately to the position of the upper left lateral incisor, crossing the midline. The sequestrated fragment involves the lateral margin of the nasal cavity. There is bilateral moderate mucosal thickening in the maxillary sinuses. Extensive periosteal reaction extending from the midline of the mandible to the left molar region is evident in keeping with chronic osteomyelitis secondary to MRONJ.

Table 1 Summary of cases

Discussion

ONJ associated with antiresorptive therapy deserves distinction from other causes and diseases/medications associated with the development of osteonecrosis of the jaw. AAOMS recently published stage specific treatment recommendation for MORNJ.²² The various stages and suggested stage-specific treatment strategies are not evidence-based, and in particular, stage 0 disease is not universally accepted. AAOMS recommendations echoed those stated in previous years for BRONJ, namely supporting conservative therapy, with aggressive surgery offered only to symptomatic patients. In contrast, the MRONJ guideline report from the German Dental and the German Oral and Maxillofacial Associations refrains from recommending therapy at least for certain stages of the disease. This might be attributed to the pitfalls of current MRONJ criteria. Furthermore, due to poor guidelines specifically related to RANKL inhibitors, no agreement exists on a universally acceptable therapy strategy of such cases.

Management strategies are largely based on expert opinion rather than experimental data. It includes prevention, conservative and surgical modalities. Prevention of the condition is the gold standard. It is highly recommended all patients have a comprehensive dental examination and preventive dentistry (pre-emptive extraction of unsalvageable teeth and optimised periodontal health) before commencing antiresorptive therapy.^23,24 Oral hygiene should be kept meticulous during the course of therapy as periodontal disease and associated bacteria claim to be implicated in this condition and also observed in these cases.

The success rate of conservative treatment regimens range from less than 20% ^25,26 to above 50%^27,28 although some cases become chronic and develop complications.²⁹

Microbial cultures from areas of exposed bone are not always helpful since normal oral microbes are isolated. However, when there is extensive soft tissue involvement, microbial cultures may help to define comorbid oral infections, which may guide the selection of an appropriate antibiotic regimen.³⁰

Regardless of the stage of disease, areas of necrotic bone that are a source of chronic soft tissue irritation and loose bony sequestra should be removed or recontoured so that soft tissue healing can be optimised. This is in line with our clinical experience. The extraction of symptomatic teeth within exposed, necrotic bone should be considered as it appears unlikely that extraction will worsen the established necrotic process. Otherwise, surgical resection of necrotic bone should generally be reserved for refractory or advanced cases.³¹ Resection may occasionally result in even larger areas of exposed and painful infected bone.³²

A recently published MISSION study⁷ reported that the AAOMS system misclassified/ underestimated the severity of the disease at a rate of about 1 in 3, in particular in patients suffering from MRONJ stage 1 and 2. The authors conclude that these findings may explain why the treatment of stage 3 ONJ, namely surgery with success rate over 85%^33,34, has been deemed to be more predictable and therefore yields more favourable outcomes than the treatment of stages 1 and 2.³⁵

Denosumab is characterised by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. This is in line with our findings since cessation of denosumab in two cases helped to improve their symptoms significantly.

MRONJ has been reported to occur after a mean administration period of 39.3 months and 35 infusions in oncology patients.²³ It is interesting that all published cases of denosumab-related ONJ occurred early after commencement of therapy, independent of the number of previous administrations.^36,37 In our experience, all patients developed MRONJ within the first 3 months of teeth extractions; well ahead of the reported period and number of administrations of denosumab.

Furthermore, all four cases have had extensive lytic lesions developed following removal of a single tooth. The common radiographic findings in all cases include:

• non-healing extraction socket
• areas of focal and diffuse sclerosis
• thickened lamina dura
• early sequestrum formation
• reactive periosteal bone
• osteolysis of cortical and spongious bone

These findings, although common in MRONJ cases, have had extensive bony involvement and rapid progression of ONJ, demonstrating a far more aggressive nature of the disease compared to that seen with BPs.

In our experience, not all patients are adequately informed of the risks and adverse events of denosumab therapy. This highlights the importance of educating patients and inter-professional communication regarding the prevention and best management of MRONJ cases. In one of the cases, the lack of patient education concerning denosumab side effects and the failure of inter-professional communication had a detrimental effect on the patient’s overall management and subsequently patient’s oral health.

Table 2 Important Points

Conclusion

We present our experience with denosumab-related ONJ from Sheffield Teaching Hospital’s NHS Trust. This case series should contribute to the existing sparse clinical literature on this topic. The pathogenesis, treatment and outcome of ONJ are complex and multifactorial. Patients treated with denosumab may be more prone to developing ONJ even without a precipitating dental event. ONJ may have a more aggressive profile and develop significantly earlier in patients receiving denosumab. Prevention of ONJ still remains the most important goal, and this is most directly accomplished by avoiding invasive dental procedures and establishing inter-professional communication.

Introduction

Postgraduate medical training should equip trainees with the skills, knowledge and attributes for independent practice¹. They need to be equipped with the skills to become lifelong learners and continually develop their abilities throughout their careers by learning from colleagues, mentors, patients and disease. The challenge for clinical teaching is how to provide an optimal learning environment in which trainees can achieve their competencies for practice within a defined training rotation; both the limitations in the number of hours within a working week and the balance between learning and service commitments all can negatively impact on the educational experience of trainees². Moreover, trainees need to balance their own development of skills, knowledge and attributes for independent practice against the requirement to provide high quality and safe healthcare³. The appropriate level of supervision must be provided to trainees performing any patient interaction and this is gauged by the trainer-trainee relationship, regular assessment and feedback. The clinical workload of a trainee needs to be finely balanced between overstretching them with tasks outside their competencies and being left with all the routine and menial tasks⁴. Thus whilst trainees should work within their competencies, they must be given the opportunities to expand their repertoire of skills, which may result in errors (and potentially patient harm) – supervision should limit these errors, which should be reflected on to provide a learning opportunity within a ‘no-blame’ culture⁵. As a trainee gains competence of their necessary skills, the amount of supervision required can be stepped down, until distant supervision (i.e. advice via a telephone) may be all that is required.

An understanding of how each learning environment within the hospital setting can be maximized may enhance the learning opportunities conferred upon trainees. Both technical skills and the professional attributes of being a clinician can be learnt in clinical and non-clinical environments. These learning environments will be explored in the subsections below.

Bedside Teaching and Ward Rounds

Bedside teaching is a stalwart of medical education, allowing clinical history and examination to be performed under guidance, in an appropriate setting and with relevant clues (observation charts, oxygen, etc.) present. This patient-trainee interaction provides an opportunity to develop professionalism and communication, and can also be the source of training of diagnostic techniques ranging from venesection and cannulation to more invasive techniques (e.g., pleural aspiration, drainage of ascitic fluid)¹.

Presentation of patients during ward rounds allows a professional conversation between trainees and trainers to occur, which justifies their role in management and provides an insight into understanding and thought processes⁶. The multidisciplinary nature of rounds creates a community of practice⁷, allowing social learning to occur, and an opportunity to voice differing perspectives on patient care³. In order to maximize these learning opportunities, learning objectives can be discussed prior to commencement and reflection undertaken once they it has been completed⁶. Teaching rounds should be carried out when the ward is quiet, at a suitable pace, with regular questioning and opportunities for trainees to ‘lead’ the process⁸. Factors that hinder this educational process include time pressures, patients not being available, and the availability of trainees⁸.

Outpatient Clinics

Outpatients provides a mixture of new and follow-up patients that enables a trainee to learn management of patients in an ambulatory setting. Trainees may be in the same room as their supervisor (learning the basics of the consultation), or can practice semi-autonomously as their experience increases (with discussion with their supervisor as required); they must select an appropriate investigation and treatment plan, with a time frame for review, once the investigation or intervention has been performed³. Outpatient teaching is more highly valued by trainees and students compared to ward based tuition⁹. Factors that hinder this educational opportunity include room availability, time constraints, staffing levels and attitudes to teaching⁹.

Operating Theatre and Interventional Suites

Invasive procedures should be performed by adequately trained (or supervised) personal in the relevant area of the hospital (e.g. endoscopy, interventional radiology suites, theatre), with the necessary equipment and monitoring for the technique to be performed. Even before patients enter these environments, trainees have an opportunity to review the patient and their relevant investigations, discuss the procedure with the patient and obtain consent for the intervention¹. Trainees can learn a wide spectrum of skills within these environments including both technical (both procedural related and anesthetic related) and non-technical skills, including Human Factors, anatomy, identification of instruments, aseptic technique, effective hand-washing and donning of surgical gowns¹⁰. Teaching invasive procedures represents a dichotomy for clinicians, not only do trainees need to gain exposure and experience in the relevant technique, but patients need to be prevented from undue harm. Prior to undertaking an intervention, trainees should be familiar with the relevant anatomy and physiology of the system they are about to operate upon, will have watched the procedure being performed and may have learnt the basics of the procedure in a simulated setting.

Trainees must to be able to self-reflect on their own skills and record of the number of procedures they have performed (which can act as a proxy for ability) to ensure that the correct level of supervision is provided alongside an intervention of suitable difficulty. Trainers need to be sure that their trainees have the necessary skills and knowledge to perform a technique, with experience often being gained in a stepwise reflecting both the difficulty of intervention and the gaining of skills, competence and confidence by the trainee¹¹. This skills acquisition should be accompanied by regular discussion and feedback to maximise learning opportunities; when no supervision is available, trainees should consider video-recording the procedure as this allows reflection and review at a later date. A video diary can also be used as a portfolio of a trainee’s repertoire from beginner to expert during their training rotation. The challenge for trainees is to achieve competence in the relevant invasive technique within their training rotation; the number of interventions required to gain competence will vary between each trainee and technique¹¹.

Handover

Handover allows the care of patients to be transferred from one group of individuals to another on a temporary or permanent basis. Handover confers an opportunity to present a clinical synopsis of patients with key information to ensure continuity of care and patient safety is maintained³. Most handovers are trainee led which provides an opportunity for peer learning to occur, checking comprehension and sharing interesting cases or tips for practice¹². Handovers should be considered to be a high risk procedure, as communication errors can result in vital information being omitted; as such the process should be undertaken in suitable environment away from distractions, in a structured written and oral manner supported by an electronic format¹². A further review at the patient’s bedside can be performed if required, which can highlight high risk patients.

Multidisciplinary Team Meetings

Multidisciplinary team (MDT) meetings are small formal meetings focused on all aspects of a patient’s care that involve a wide range of medical personal, nursing staff and allied health care professionals¹. Meetings ensure that evidence-based guidelines are followed, and help to streamline management, removing unnecessary delays in treatment and improving cost effectiveness. MDTs represent a Community of Practice⁷ allowing social learning to occur as each individual can share their relevant expertise; MDTs enable best practice to be shared and help break down barriers between different specialties.  Trainees can learn from the didactic teaching that occurs within the MDT (in relation to clinical details, investigation and management), but can also contribute to the meetings and practice their presentation skills.

Morbidity and Mortality Meetings

Morbidity and Mortality (M&M) meetings can help ascribe accountability and be used to highlight improvements in patient safety. They provide an opportunity for professional education, especially if the discussion can be held within a no-blame culture, and the meeting can voice discrepancies in how to manage patients, especially in ambiguous situations¹³. Trainees may be tasked with presenting a case and the potential learning aspects associated with patient care.

Grand Rounds/Formal Teaching

Grand rounds are traditional formal teaching opportunities that typically revolve around a case, whereby salient findings are presented prior to a discussion of management. These meetings allow opportunities for trainees to present cases and learn management, but their educational benefit may be decreasing as they are being replaced with lectures with limited clinical relevance¹⁴. However “audience apathy, deteriorating decorum and shrinking attendance” have diminished these learning opportunities¹⁴. Targeted teaching and the establishment of learning objectives for trainees can improve the educational content and the provision of feedback to the speakers can also enhance these meetings.

Journal Club

Journal clubs confer an opportunity for current scientific research and developments to be presented, critiqued and discussed by trainees. These clubs confer an opportunity to appraise the current literature and how that can be translated into evidence based patient care¹⁵. Journal clubs tend to be both voluntary and occur outside of working hours, resulting in highly motivated groups of participants whom are protected from interruptions.

eLearning and mLearning

Electronic learning (eLearning) and multimedia learning (mLearning) enable trainees to work informally, away from desks and computers, and at their own pace through a series of educational modules. Any intervention that engages trainees and promotes learning should be encouraged and these online learning platforms can be combined traditional learning resources should be promoted to ensure that all aspects of the curriculum are covered. mLearning in particular  can be ‘dipped into’ allowing the learner optimal flexibility of how and when they want to use it. elearning can be referred to during point-of-care patient interactions when a trainee is unsure of how to proceed with patient management¹. These increasingly important and under-utilized resources should be supported by educational institutions that support both undergraduate and post graduate trainees. By developing a virtual learning environment, individual tailored learning programs can be created that allow a trainee to develop and control their own online learning¹⁶.

Simulation

Simulation is becoming increasingly important for medical training. , anything can be simulated from learning clinical skills to human factors training, for both individuals and teams, focused on patient care and current medical practice in both the undergraduate and postgraduate setting. The availability of simulators coupled with competency based training and a decreased amount of training within the workplace has led to an increase use of this teaching format¹. In addition, trainees need to understand how to use certain pieces of equipment prior to employing them on patients and this familiarity can only be gained in a simulated setting. Simulation can either occur within the workplace (allowing point-of-care simulation to see how teams react in a situation) or on formal taught courses; it can be low-technology and cheap (e.g., tying surgical knots on the back of a chair), but can also be high-fidelity and expensive (e.g., a virtual reality training simulator for laparoscopic operations), or use animal or cadaveric tissue. Simulation that increases trainee’s familiarity with certain techniques is likely to improve their clinical performance, decreasing potential patient harm and shorten the time taken for trainees to achieve competence¹. A simulation should be completed with feedback from the supervisor to ensure that trainees gain the most from the session and clarify any facts or concerns about the simulation; a video recording of the session can also enable participants to reflect on their performance in a manner that is almost impossible in everyday clinical practice.

Introduction

Chest pain accounts for 1% of all GP consultations, but in only 8%-18% of cases is it an indicator of underlying ischemic heart disease.¹ Given the potential diagnostic uncertainty associated with chest pain at initial presentation, specialist evaluation of patients in a Rapid Access Chest Pain Clinic (RACPC) is of value and represents an important process in the evaluation of symptoms. These clinics were established with the aim of providing rapid outpatient assessment of patients with suspected cardiac disease in order to permit earlier provision of appropriate treatment and investigations where required.

Stable chest pain typically presents as angina, a triad of dull central chest pain, brought on with exertion and relieved by rest or GTN spray. The aetiology is usually stable atherosclerotic plaque disease which is associated with low mortality and can be treated with oral anti-anginals, as demonstrated by meta-analyses and the landmark COURAGE study. ^{2, 3}

NICE Clinical Guideline 95 (NICE CG95) suggests that choice of initial investigation for stable chest pain should be guided by a patient’s pre-test probability of having CAD. Calculations of the pre-test probability take into consideration a patient’s age, gender, cardiac risk factors and symptoms. Patients are defined as high risk of cardiac disease if they have diabetes, smoke or have hyperlipidaemia (total cholesterol >6.47mmol/litre). Patients with none of the above are considered low risk. Symptoms are defined as “typical angina” if the pain is: 1) constricting discomfort in the front of the chest or in the neck, shoulders, jaw or arms; 2) is precipitated by physical exertion and 3) is relieved by rest or GTN spray within approximately five minutes. Pain is defined as “atypical angina” if only two of the above criteria are met and defined as “non-anginal” if one or none of the above criteria are met.

NICE pre-test probabilities of CAD (Table 1), are based on a version of Diamond and Forrester’s pre-test probabilities published in 1979, modified using data from Duke’s cohort study, published in 1993.^{4, 5, 6} Recent studies suggest that these NICE pre-test probabilities may overestimate the prevalence of CAD in a primary care population and may risk over investigating patients.^{7, 8} In addition to having financial implications, this may cause patients undue anxiety and unnecessarily put them at risk of complications.

Table 1: NICE Clinical Guideline 95 pre-test probabilities table.

Each cell represents the percentage risk of each group of patients having CAD, based on their typicality of symptoms, gender, age and cardiac risk factors (lo, low and hi, high)⁴

ESC guidelines utilise an updated, validated model of the Diamond-Forrester model by Genders et al. to create pre test probabilities of CAD (Table 2), based on patient’s age, gender and typicality of symptoms. ^{9, 10}

Table 2: ESC guidelines clinical pre-test probabilities in patients with stable chest pain symptoms 

Each cell represents likelihood of each group of patients having CAD, based on typicality of symptoms, age and gender.⁹

We hypothesised that strict adherence to NICE guidelines results in over-estimation of the pre-test probability of CAD and therefore over-investigation of patients presenting with stable chest pain. ESC guidelines may offer more accurate pre-test probabilities of CAD and allow a more targeted and cost-effective use of investigations.

Methodology

Clinic records of all patients who attended the RACPC at Tunbridge Wells Hospital between July 2005 and December 2012 were reviewed. This service is run by a cardiology specialist. Patient demographics, cardiac risk factors and information regarding the nature of patient symptoms were collected prospectively and completed at the time of the patient’s RACPC appointment. Results of cardiac investigations were collected from paper and computerised records, and included diagnoses of significant CAD made following invasive coronary angiogram. These results were compared with patients’ pre-test probabilities of CAD calculated using both NICE and the ESC’s calculation methods. Outcome and readmissions were obtained from electronic records from the Maidstone and Tunbridge Wells NHS Trust computer records retrospectively.

Results

Study population

A total of 1968 records were reviewed. 59% (n = 1162) of patients were male and 41% (n = 806) were female. Their mean age was 60 years. At initial assessment, 69.8% patients (n=1373) had non-anginal chest pain, 19.5% (n=383) had atypical angina and 10.8% (n=212) had typical angina, based on the NICE guideline definitions of chest pain.

97.2% (n= 1912) patients underwent further investigation; 15% (n=256) of these were subsequently diagnosed as having significant CAD, accounting for their symptoms. The 2.8% (n=56) of patients who did not undergo investigation either chose not to, were unable to, were lost to follow up, or were diagnosed as having a non-cardiac cause of their symptoms at the initial RACPC appointment.

NICE CG95 pre test probabilities compared against cohort data

Table 3: NICE guidelines 95 pre test probabilities compared against cohort data

Each cell represents the proportion (%) of cohort patients from each group who were diagnosed with CAD. We have colour-coded cells to represent the NICE estimated pre-test probability of CAD in each group. Red cells represent 61-90+% probability, pink cells represents 30-60% probability, blue cells represent 10-29% probability and white cells represents <10% probability of CAD according to NICE Guidelines. “ – “ marks a cell where pre-test probabilities of CAD could not be calculated for cohort patients.

Table 4: A comparison of NICE pre-test probabilities and cohort patient data.

The risk of CAD as predicted by NICE guidelines 95 on the left compared with the actual number of cohort patients in each category and the proportion of those patients diagnosed with significant CAD.

The average discrepancy between the pre-test probability and actual incidence of CAD in cohort patients was 28% (range 20% - 88%). In 48% of cells in the NICE CG95 pre-test probability table (Table 1) the pre-test probability of CAD was overestimated by 30% or more (Table 3). A marked discrepancy between pre-test probability and actual incidence of CAD was found between “high risk” and “very low risk” patients. On average, high risk patients had an overestimated pre-test probability of 34.3 – 40.9% per cell compared with low risk patients whose pre-test probability was only overestimated by 6.5% (Table 3).

The cells highlighted in dark red in table 3 represent high risk patients whose pre-test probability was of 61-90+%, according to NICE CG95. In our cohort, only 31.2% (n=214, 95% CI 27.6-34.5) of high risk patients in this category were diagnosed with CAD. On average, actual incidence of CAD compared with pre-test probability was overestimated by 34.4% – 40.9% in each cell.

The pink cells in table 3 represent medium risk patients with a pre-test probability of CAD of 30-60%, according to NICE CG95. In our cohort, only 4.4% (n=24, 95% CI 3.0 – 6.5) of medium risk patients had a positive angiogram (Table 4). The average overestimate of actual incidence against pre-test probability was 35.9%.

The cells highlighted in blue in table 3 represent low risk patients with a pre-test probability of CAD of 10-29%, according to NICE CG95. In our cohort, only 2.5% (n=7, 95% CI 1.2 – 5.0) of low risk patients were diagnosed with CAD (Table 4). On average, the pre-test probability of CAD exceeded the found incidence of CAD by 18.6% (Table 3).

The white cells in table 3 represent very low risk patients with pre-test probability of CAD <10% according to NICE CG95. In our cohort, only 0.28% (n= 1, 95% CI 0.1 – 1.6) of patients were diagnosed with CAD. Average overestimation in this group was 6.5% in each cell.

ESC guidelines pre test probabilities compared against cohort data

Table 5: A comparison of ESC pre-test probabilities with cohort patient data.

Each cell shows the proportion (%) of cohort patients from each group diagnosed with CAD. Each cell is colour coded to correspond with the ESC estimated pre-test probability. Dark red cells represent >85% probability, pale pink cells represent 66-85% probability, pale blue cells represent 15-65% probability and white cells represent <15% probability.

Table 6: A comparison of ESC pre-test probabilities and cohort patient data

The risk of CAD as predicted by ESC guidelines on the left compared with the actual number of cohort patients in each category and the proportion of those patients diagnosed with significant CAD.

The average discrepancy between pre-test probability of CAD, according to the ESC’s risk stratification table, and actual incidence of CAD in cohort patients was 20.7%. In 28% of cells, the pre-test probability of CAD exceeded the found incidence of CAD by 30% or more (Table 5).

The cells highlighted in dark red in table 5 represent very high risk patients with a pre-test probability of CAD greater than 85%, according to ESC guidelines (Table 5). 73.4% (n= 58, 95% CI 63.7 – 82.7) of cohort patients in this high-risk category were diagnosed with CAD (Table 6). On average, incidence of CAD in each cell has been overestimated by 13% in this category.

The cells highlighted in pale pink in table 5 represent high risk patients, with a pre-test probability of CAD of 66-85%, according to ESC guidelines. 58.5% (n=103, 95% CI 51.1 – 65.5) of cohort patients in this high-medium risk category were diagnosed with CAD (Table 6). On average, the pre-test probability of CAD exceeded the found incidence of CAD in each cell by 17.7% (Table 5).

The cells highlighted in pale blue in table 5 represent medium risk patients with a pre-test probability of CAD of 15-65%, according to ESC guidelines. 6.4% (n=93, CI 5.3 –7.8) of cohort patients in this risk category were diagnosed with CAD (Table 6). On average, the pre-test probability of CAD exceeded the found incidence of CAD by 24.1%in each cell (Table 5).

The cells highlighted in white in table 5 represent patients whose pre-test probability of CAD was less than 15% according to ESC guidelines. Only 0.76% (n=2, 95% CI 0.2 –2.7) of cohort patients in this risk category were diagnosed with CAD (Table 6). On average, pre-test probability of CAD exceeded found incidence of CAD in each cell by 6.2% (Table 5).

Discussion

Only 15% of a total of 1968 patients referred to RACPC were diagnosed with significant CAD. The majority (70%) of referred patients had “non-anginal” chest pain and low pre-test probabilities of CAD, reflecting the importance ascribed by General Practitioners of ruling out ischemic heart disease as the underlying cause for chest pain, even in low risk patients. This may not be surprising given the large media attention to heart disease and sustained campaigns for early warning signs of heart attack in the British media. It is therefore of great public interest for cardiac disease to be identified.

NICE CG95 pre test probabilities compared against cohort data

Comparing cohort data to the pre-test probabilities of CAD outlined in NICE CG95, NICE have overestimated the number of patients likely to have CAD in the majority of groups. Strict adherence to NICE CG95 therefore carries the risk of over-investigating patients. NICE recommend CT calcium scoring as the first line investigation for patients with a low (10-29%) pre-test probability of CAD. 284 patients fall into this category and only 7 patients were shown to have CAD. This means that 40.5 patients need to be treated in order to identify 1 positive patient (NNT= 40.5).

In patients with a medium (30-60%) pre-test probability of CAD, NICE recommends functional imaging as the first line diagnostic investigation. In our cohort 544 patients would undergo functional imaging, but only 24 of these patients would be diagnosed with CAD, NNT=22.7.

Finally, in patient groups with a high (61-90%) pre-test probability of CAD, NICE recommends invasive coronary angiography as the first line diagnostic investigation. In our cohort of 1968 patients, 691 patients had a high pre-test probability of CAD, and 214 had significant coronary artery disease on angiography, NNT= 3.2.

Although invasive coronary angiography is considered the gold standard investigation for diagnosing CAD, and permits simultaneous therapeutic intervention, the procedure is not without risk, particularly in elderly patients and those with renal impairment.¹¹ Furthermore, invasive angiography is expensive and is costed by the East Kent Hospitals University NHS Foundation Trust at £1166.02 per procedure (private correspondence).

NICE CG95 offers no guidance on managing patients who have a <10% pre-test probability of CAD. 347 of our cohort patients fell into this very low risk category and only 1 was diagnosed with CAD. Therefore, NICE CG95, if strictly adhered to, would have missed one diagnosis of CAD in our patient cohort.

ESC pre test probabilities compared against cohort data

ESC guidelines tend to offer more conservative estimates of pre-test probability of CAD compared with NICE guidelines. Using the ESC’s risk stratification table, almost all patients, except those with over 85% pre-test probability and those with less than 15% pre test probability, would be investigated for chest pain. This is due to their claim that non-invasive, image-based diagnostic methods for CAD have typical sensitivities and specificities of around 85%, so that roughly 15% of these investigations could be yielding false results. Hence, due to these inaccuracies, in patients with pre-test probabilities of CAD below 15% or above 85%, ESC state that performing no test at all could provide fewer incorrect diagnoses.⁹

In our patient cohort, 79 patients had very high (>85%) pre-test probability of CAD, but only 58 patients (73%) were diagnosed with CAD. For this patient risk group, ESC guidelines suggest that further investigation may not be necessary and that a diagnosis of CAD may be assumed. Thus, applying ESC guidelines to our cohort could result in 21 patients being incorrectly diagnosed with stable angina, and more serious causes of chest pain, for example pulmonary emboli or gastric ulceration, may be missed. However, in practice, it is likely that many patients in this very high pre-test probability category would have undergone angiography, because patients who have "severe symptoms" or who are clinically thought to have "high risk coronary anatomy" should be offered an invasive angiography with or without pressure wire studies. The vagueness of the guidelines allows interventionists to interpret this in the clinical context.

In ESC guidelines, invasive coronary angiography is not specifically recommended as a first line investigation for stable angina, regardless of the pre-test probability of CAD. In patients with a high (66-85%) pre-test probability of CAD, ESC guidelines recommend non-invasive functional imaging first line. Of the 176 patients who fell into this category, only 102 (58.0%) patients were ultimately diagnosed with CAD.

In patients with medium (15-65%) pre-test probability of CAD, ESC guidelines advise exercise ECG testing (or non-invasive imaging for ischemia if local expertise is available) as first line diagnostic investigations. Of the 1451 patients which fell into this category, only 93 were diagnosed with CAD, NNT= 15.6. Fortunately, exercise ECG testing would not expose the patient to potentially harmful radiation or medication, but their poor diagnostic power may result in the need for further investigations, despite a negative result.

In patients with low risk of CAD (<15%) ESC guidelines suggest making an assumption that the patient does not have CAD and advocates conducting no further investigations. In our cohort, 263 patients fell into this low risk category, two (0.8%) of which were diagnosed with CAD.

The ESC guidelines appear to have higher specificity than the NICE guidelines, and only two patients would have been missed had ESC guidelines been adhered to, compared to one patient missed if NICE guidance was used. Thus, although highly sensitive, ESC guidelines when applied to our cohort have lower sensitivity than NICE guidelines.

Comparison of number of investigations

Following ESC guidance for our cohort of patients would have resulted in fewer diagnostic invasive angiograms being performed than if NICE guidance had been followed. ESC guidance only recommends invasive angiography if first line, non-invasive investigations generate positive results. Overall, however, ESC guidance would result in a greater number of overall investigations being performed.

In total, NICE advises that all 691 of our high risk cohort patients should undergo invasive angiography as a first line investigation. 544 with medium risk should undergo functional testing first and 24 of these patients (assuming an angiogram would follow a positive result) would go on to have invasive angiography. 284 low risk patients should undergo CT calcium scoring first, of which 7 would go on to have functional imaging and angiography if the above logic is followed. This generates a total of 1557 investigations; 722 angiograms, 551 functional imaging investigations and 284 cardiac CT scans.

In comparison, using ESC guidance, 176 of our high risk patients would have functional imaging investigations, 103 patients with positive results would then undergo invasive angiography. 1451 patients would receive exercise ECGs, of which 93 with positive results would undergo functional imaging and invasive angiography. This generates a total of 1916 investigations; 196 angiograms, 269 functional imaging investigations and 1451 exercise ECGs.

If we assume that stress echocardiograms are used as “functional imaging” we can estimate costs for our cohort when applying each set of guidelines. Costs for each investigation are supplied by East Kent Hospitals University NHS Foundation Trust and are as follows: Outpatient elective coronary angiograms are costed at £1,166.02; stress echocardiograms are costed at £132.30; exercise ECGs at £40.26 and CTs of one area at £102.47 (private correspondence). If we were to apply NICE guidelines to our cohort, £841,866.44 would be spent on angiograms, £72,897.30 would be spent on stress echocardiograms and £29,101.48 on CT scans. This is a total of £943,865.22 on investigations.

If we were to apply ESC guidelines to our cohort, £228,539.92 would be spent on coronary angiograms, £35,588.7 would be spent on stress echocardiography and £58,417.26 would be spent on exercise ECGs. A total of £322,545.88 would be spent on investigations. Overall, this is £621,319.34 cheaper than applying NICE guidelines.

Limitations of study

This study is based on data from a single site and may not be nationally representative. The final diagnosis was made clinically by an experienced interventional cardiologist, which introduces subjectivity and the risk of interpreter bias. Not all patients underwent the gold standard of invasive coronary angiography to demonstrate the presence of CAD. However, all patients were seen and fully assessed by a cardiologist and 97% underwent investigations if deemed necessary.This study has all the limitations of a registry study. In addition, costs for investigations may vary throughout the country, and indeed the world, with varying expertise available.

Conclusion

In conclusion, strict adherence to NICE CG95 over-estimates the pre-test probability of CAD in our local population group. This is consistent with previous studies conducted in South London where there is a larger Afro-Caribbean population, as well as with studies conducted in the North of England.^8,9 Adherence to ESC guidelines in place of NICE guidelines may enable a more targeted and cost-effective use of investigations. Strict application of the ESC guidelines to the study cohort would have resulted in investigations costing an estimated £322,545.88, compared to £943,865.22 if NICE guidelines were applied. However, conducting fewer investigations carries greater risk of misdiagnosis, and using ESC guidelines in isolation introduces the possibility of assuming CAD in patients without conducting investigations to confirm this.

It is advisable that local cardiology departments audit their stable chest pain guidelines to ensure that the interpretation of pre-test probabilities is in keeping with the local population. Unfortunately there is no ideal policy and local protocols should reflect the local population.

Background

Global recruitment in psychiatry has been falling for several decades because medical students and graduates have been finding it consistently unattractive ^1,2. An analysis of the career choices of newly qualified doctors in the United Kingdom (U.K.) found the same trend from 1974 to 2009; psychiatry was the first career choice for only 3-5% of medical graduates annually³. In the U.K., lack of recruitment into psychiatry had reached a crisis point by 2003 when 15% of all unfilled consultants posts in England were in psychiatry and the Royal College of Psychiatrists was finding recruitment into specialist psychiatry posts increasingly difficult^4,5. In 2012, only 78% of the Core Training year one (CT1) posts in psychiatry were filled; a serious shortfall which was overcome by overseas recruitment up until changes in immigration rules.

The factors that seem to dissuade medical students from taking up psychiatry as a future career may include: stigma, bad prognosis of psychiatric disorders, poor scientific base of psychiatry, ‘bad-mouthing’ from medical colleagues, lack of respect among peers & public, threats of violence from patients and lack of resources^1-5. However, there is evidence to suggest that many students’ attitudes towards career choice changed in a positive direction after working in psychiatry due to the perceived ‘job satisfaction’, ‘life-style’, ‘training available’ and ‘multidisciplinary approach’³.

Psychiatry has previously been ranked higher in career choice at the end of students’ clinical year⁶. To ensure a stable psychiatric workforce for the future, there is an obvious need to motivate current and future cohorts of young doctors to take up psychiatry as a career. Das & Chandrasena (1988) found that attitudes changed positively towards mental health following clinical placement in this specialty⁷. It is also known that medical students’ attitudes to psychiatry and career intentions can be improved by their experiences of teaching⁸. Students were found to develop more positive attitudes when encouraged by senior psychiatrists, had direct involvement in patient care, or saw patients respond well to treatment. Improvement in attitudes during the placement was also related to an increased intention to pursue psychiatry as a career.

Previous research into attitude to psychiatry as a specialty and career choice seems to have produced conflicting results and most of it was carried out among medical students. Since career choices in the U.K. are actually made in the first clinical year following graduation, we carried out a survey among a recent cohort of foundation year one (FY1) doctors in the South East England before and after their first clinical year.

Method

Our study sample consisted of all FY1 doctors (n=101) in one region of South East England. They participated in the study at the beginning and then at the end of their first clinical year. We used a 20–item questionnaire devised by Das & Chandrasena(1988) to ascertain their perceptions and attitudes towards psychiatry before they commenced their first clinical placement. The questionnaire was sent to them via their Medical Education Managers (MEMS). It was handed out to the FY1 doctors as part of their induction pack for completion along with a study information sheet.

At the end of their first year of working, the participants were asked to complete an amended version of the questionnaire. This included two additional questions which ascertained whether the doctor had an opportunity to work in a psychiatric post, or had any experience of psychiatry in practice (such as taster days or cases in A&E). These amended questionnaires were sent to the foundation doctors electronically via their MEMS for completion.

The data was collected and entered into a spreadsheet to prepare descriptive statistics. Comparisons for before and after exposure to psychiatry, and between the psychiatry and non-psychiatry groups were made using the chi-square test. As the data was binary, a latent class model was developed using LatentGOLD software⁹ to explore the associations between different items in the questionnaire. Responses from the questionnaires were coded as: responses which agree with a positive attitude to psychiatry or disagree with a negative attitude were coded as +1; those not sure were coded as 0; and responses which agree with a negative attitude to psychiatry or disagree with a positive attitude were coded as -1.

Results

A 100% (n=101) response rate was obtained for the first set of questionnaires completed at the beginning of the year. However, there was a significant drop in the number of questionnaires completed at the end of the year - a 53.5% response rate (n=54) generally but 61.1% (22 out of 36) for those FY1 doctors who had the opportunity or access to a post in psychiatry within their clinical year.

Initial cohort at beginning of the clinical year vs. those with no exposure to psychiatry at the end

Table 1 shows the group means for each questionnaire item, for the whole cohort at the beginning of the year compared to those with no exposure to psychiatry by the end of the year.

Table 1: All FY1 doctors before training placements started (initial cohort) versus FY1 doctors without a psychiatric post after FY1 training

Those FY1 trainees who had not worked in psychiatry during the year were significantly more positive (p = < 0.05) for psychiatry’s future, psychiatrist being better at patient communication and not over-medicating their patients. However, they remained significantly less convinced as compared to the whole cohort about psychiatry’s intellectual attraction or taking it up as a future career.

Initial cohort at beginning of the year vs. those with exposure to psychiatry at the end

Table 2 shows the group means for each questionnaire item, for the whole

cohort at the beginning of the year compared to those with exposure to psychiatry at the end of the year.

Table 2: All FY1 doctors before training placements started versus FY1 doctors with a psychiatric post during FY1 training

After a psychiatry placement, significant positive differences (p=<0.05) were observed in their responses to medical staff’s view of psychiatry, future of psychiatry and place of Electro Convulsive Therapy (ECT) in modern medicine. While there was a positive trend in most responses in favour of psychiatry, trainees remained negative about psychiatry’s status, its scientific base, curriculum & training and taking up psychiatry as a future career.

Those exposed to psychiatry vs. those not exposed to psychiatry

Table 3 compares responses between FY1 doctors exposed to psychiatry during the clinical year and those who were not.

Table 3: FY1 doctors who had a psychiatric post versus those who did not have one

Those exposed to psychiatry agreed more often that non-psychiatric medical staffs were critical of psychiatry compared to the group not exposed to psychiatry. They also had comparatively negative responses for psychiatrists not abusing legal powers and to have the legal power to treat someone against their will. Trainees exposed to psychiatry also felt significantly (p=<0.05) positive towards psychiatry being intellectually comprehensive and adopting it as a career. However, they were less enthusiastic about psychiatrists treating patients against their will and psychiatry being the expanding frontier of medicine.

Discussion

In this study, we have ascertained attitudes of a regional cohort of FY1 doctors towards psychiatry as a specialty and as a career choice. Our findings are similar to previous research carried out among medical students, which found that there were generally negative attitudes towards psychiatry as a specialty and career choice but fairly positive attitudes towards the role of psychiatry in medicine and in society in general^1-5,10. Like others, we also found that personal experience of psychiatry placement can improve trainees’ view of psychiatry as a specialty and as a future career ^3,11.

It was interesting to find out that after a year in clinical practice but without any experience of psychiatry, trainees’ attitudes towards psychiatry as a specialty had been positive. It is difficult to know the exact reason but we can speculate that this respect for the specialty may have developed when they experienced limitations of the other specialties in medicine and/or perhaps due to the positive professional encounters with psychiatrists at the Accident & Emergency (A&E) or with psychiatric liaison teams during ward consultations. As opposed to previous research¹¹, it was heartening to note that the group with no exposure to psychiatry agreed that non-psychiatric medical staff were not critical of psychiatry; a possible sign of reduced stigma for psychiatry within the medical profession.

Despite exposure to psychiatry, FY1 doctors’ attitudes to psychiatry’s status, scientific base, curriculum & training and career choice remained somewhat negative. Similar results were found by Lyons et al¹¹ when they assessed students’ attitudes towards psychiatry after a clerkship in the specialty. There was a significant decrease in negative & stigmatising views towards mental illness after the clerkship, but no significant improvement in students' interest in psychiatry was detected¹. Goldacre et al (2013) also acknowledged mixed outcomes of early experience of working in psychiatry as it might discourage some doctors. While highlighting positive effect of the doctors’ experience of the speciality, they also cited it as a negative factor that influenced some doctors who had previously considered psychiatry as a career³.

Our study has limitations because of having a small sample and being carried out in one small region of the country. It is also worth mentioning that the group exposed to psychiatry may not have had a psychiatry placement as it also included those who had had taster days or experience in A&E. The brevity of these latter exposures cannot give someone a real sense of the specialty. The nature of this and the overall experience needs to be differentiated and the exposure quantified in the future studies. Our study findings also need to be replicated with future cohorts and in other regions for confirmation because FY training programme in the U.K. is relatively recent and placements in psychiatry have evolved⁴ over the last few years through closer collaboration between different stakeholders in the Foundation Training Programmes.

Introduction

Bed bugs belong to the family Cimicidae and there are two species involved in the modern resurgence; the Common bed bug, Cimex lectularius and the Tropical bed bug, Cimex hemipterus. They are wingless insects with an oval-flat shape that allows them to hide in narrow cracks and crevices. The adults are dark brown, 4-5mm long, becoming to around 10mm when fully blood-engorged. There are five smaller juvenile stages (nymphs) that are similar in appearance, although lighter in colour. All nymphs require a blood meal to moult to the next stage, and both adults also bloodfeed for nutrition, and egg development in the case of the female. Bed bugs are solely haematophagous ectoparasites. After feeding they return to a harbourage and do not remain on the host. The main hosts are humans, but pets, bats, and birds may act as secondary hosts.

Epidemiology

In the past, bed bugs were particularly an affliction of the poor. However, in the early part of the modern resurgence it was the tourist areas and the hospitality sector that were initially impacted.^1-3 Today, bed bugs have conquered quite diverse locations, ranging from hospitals, hotels and homes, to trains, cruise ships, and even airplanes. Most commonly, bed bugs travel in comfort as stowaways in luggage, although they can be transferred via furnishing and other belongings, as well by spreading to adjoining properties. Unfortunately, exact figures on the occurrence of bed bugs are unknown, as there are no mandatory reporting requirements. Additionally, due to the stigma associated with bed bugs, many infestations are simply not reported.

During the day, the largely nocturnal bed bugs will crawl deep into crevices of bed frames and mattresses (Fig.1), or behind wallpaper, and floor moldings. Here they tend to lay their eggs, often several hundred during the female lifetime. Live bed bugs, shed nymphal skins, and dark excrement spots indicate an active infestation. At night they are attracted by carbon dioxide, heat and other host odours to a victim, from which they may take a blood meal every 3-5 days. The adult bugs can survive long periods of starvation, up to five months at 22^oC or even longer at cooler temperatures. When a host is found, they insert their mouthparts into the skin, blood feeding for 5-10 minutes. When bed bugs are in large numbers, often lines of bites occur on the unfortunate victim and this sign is almost a sure indication of the presence of the insect. The bites tend to occur along the arms and legs, down the back and across the shoulders.^4,5

There has been long speculation whether bed bugs can transmit diseases, and in fact more than 40 different pathogens have been implicated. This has included Hepatitis B and C viruses, Human Immunodeficiency Virus (HIV), and Coxiella burnetii (Q fever). Recently, research has indicated that bed bugs are capable of transmitting the agent of Chagas Disease, Trypanosoma cruzi,in the laboratory. However, to date there is not one piece of evidence that bed bugs have transmitted any pathogen to humans.^4,6

Clinical Features

During the act of feeding, saliva is injected which contains a variety of anticoagulants as well as other proteins whose function has yet to be determined. Contrary to popular belief, there is no evidence that bed bugs inject an anaesthetic. One protein, Nitrophorin, is involved in the transport of nitric oxide into the wound. This results in local vasodilation that increases blood supply to the feeding insect. The same protein can also induce a sensitivity to the bite.⁶

The diagnosis of Cimicosis is via the clinical appearance of the bite reaction and confirmation of an actual bed bug infestation (Table 1).^3,5 The most commonly affected body parts are those that are left uncovered during sleep (Fig. 2,3,4), notably the arms, shoulders and legs. In young children, the face and even the eyelids can be bitten. Rarely, however, armpits are bitten, which are often preferred by other insects and ticks (Table 2).

Figure 1: Typical appearance of bed bugs

Figure 2: Bites on the back, note the lines of bites common in moderate to large infestations

Figure 3: Bed bug bites on the arm, typical formation

Figure 4: Bed bug bites on the torso and arm

Figure 5: Bullae due to bed bug bites

Figure 6: Bed bugs, their droppings and eggs underneath a mattress

The degree of the bite reaction often depends on the level of prior exposure. With low level sensitization, individuals may develop a 1-2 cm wheal, with a small central haemorrhagic point. This haemorrhagic point can be recognized easily by diascopy. In contrast, a highly sensitized person will react immediately and may develop a wheal up to 15cm across (6 inches). If many bed bugs are present, an urticarial rash may develop as a result of the large number of bites and subsequent trauma to the area from scratching. On rare occasions, vesicles and bullae (Fig. 5) may form on the arms and legs. In the course of Cimicosis, papules that are extremely itchy may develop and can persist for several days to weeks. Due to the strong pruritus eczematous lesions, bacterial infections may occur, although this is extremely rare. There are case reports of systemic reactions such as anaphylaxis and asthma, although these are uncommon.

Through repeated exposure, some individuals may develop a tolerance to the bites. The clinical symptoms are then largely inapparent with small punctures at the bite site. Small blood spots are then the only clues that an infestation may be present.

Differential Diagnosis

Since reactions to stings and bites of various arthropods are non-specific, bed bug bites are commonly misdiagnosed. Single bites, notably that of other insects such as mosquitoes, fleas and biting midges may appear very similar morphologically (Table 2).

Consideration of where the bites are on the body can assist in the differential diagnosis. For bed bugs, lines of bites are very common in moderate to large infestations and this clinical picture is virtually unique amongst blood sucking arthropods. For the most part, the identification of the actual pest is required to confirm the diagnosis. Histologically, bed bug bites resemble perivascular eosinophilic infiltrates through the superficial and deep dermis, with minimal spongiosis.

Other possible diagnostic confounders can be various allergic reactions and other medical conditions such as urticaria, chickenpox, prurigo subacuta, and erythema multiforme.^7,8 These do not show a central haemorrhagic point in the lesion which allows a correct diagnosis. However, in young children the diagnosis can sometimes be difficult. 

Treatment

The treatment of Cimicosis is symptomatic. Local lesions can be treated with antipruritics e.g. Polidocanol 2-4% in Lotio alba (aqueous lotion) and topical antiseptic. Spirit of menthol may also be helpful. Local treatment with antihistamines is controversial. In severe reactions topical glucocorticoids such as Betamethasone may be required. In severe itching, the use of oral antihistamines is recommended. With infected bites, antibiotic therapy may be required. Uncomplicated bed bug bites tend to stop itching within 1-2 weeks, although temporary scarring from the bite may remain for several months.

Management

Treatment of patients with bed bug bites ultimately comes down to removing the source of the irritant, namely the eradication of the active infestation. Bed bugs have a typical pungent odor. This can be used to detect bed bugs through specially trained sniffer dogs that can rapidly locate the insects.⁹ Due to insecticide resistance, bed bugs are very difficult to control with traditional insecticides alone, and non-chemical means of eradication must be employed to reduce the overall insect biomass. Bed bug control should be undertaken by professionals trained in bed bug management, and the process may take some weeks to achieve.

Prevention

When travelling (1) always inspect the bed and surrounds for bed bugs hiding beneath the mattress and/or in seams of the bedding. Also, look for blood stains or small black dots (Figure 6, Table 1). (2) If present, request another room. (3) Always keep your luggage on the desktop or the luggage rack. A good preventative is to seal luggage in plastic or garbage bags during travelling, even when in transit. (4) When returning home, all clothing should be washed in at temperatures exceeding 60°C or frozen for one week with delicate fabrics. If there is no choice, then repellents containing N, N-Diethyl-meta-toluamide (DEET) should reduce the biting rate, but will not completely prevent all bed bug bites.^10,11

Bed bugs can enter homes via an array of additional ways, particularly from objects bought second hand at flea markets or thrift stores, for example wooden frames, vintage clothes, furniture and the like. These should be heat-treated for a minimum of 10-20 minutes to kill bugs and their eggs.

Introduction

Striae distensae, or stretch marks, are linear scars in the dermis which arise from rapid stretching of the skin over weakened connective tissue. It is a common skin condition that rarely causes any significant medical problems but is often a significant source of distress to those affected. Striae distensae were described as a clinical entity hundreds of years ago, and the first histological descriptions appeared in the medical literature in 1889.¹ With a high incidence and unsatisfactory treatments, stretch marks remain an important target of research for an optimum consensus of treatment. These appear initially as red, and later, as white lines on the skin, representing scars of the dermis, and are characterized by linear bundles of collagen lying parallel to the surface of the skin, as well as eventual loss of collagen and elastin. The estimated prevalence of striae distensae range from 50 to 80%.^2,3 The anatomical sites affected vary, with areas commonly affected including the abdomen, breasts, thighs and buttocks.⁴ The three maturation stages of striae include the acute stage (striae rubra) characterized by raised, erythematous striae, the sub-acute stage characterized by purpuric striae, and the chronic stage (striae alba), characterized by white or hypo-pigmented, atrophied striae.⁵ Although stretch marks are only harmful in extreme cases, even mild stretch marks can cause distress to the bearer⁶ (Table 1).

Table 1: Histological comparisons between striae rubrae and striae albae

Aetiology

Striae may result from a number of causes, including, but not limited to, rapid changes in weight, adolescent growth spurts, corticosteroid use or Cushing Syndrome, and generally appear on the buttocks, thighs, knees, calves, or lumbosacral area.⁷ In addition, approximately 90% of all pregnant women develop stretch marks either on their breasts and/or abdomen by the third trimester.⁸ Genetic predisposition is also presumed, since striae distensae have been reported in monozygotic twins.^9,10 There is decreased expression of collagen and fibronectin genes in affected tissue.¹¹ The role of genetic factors is further emphasised by the fact that they are common in inherited defects of connective tissue, as in Marfan’s syndrome.^12,13 Obesity and rapid increase or decrease in weight have been shown to be associated with the development of SD.¹⁴ Young male weight lifters develop striae on their shoulders.¹⁵ Striae distensae also occurs in cachetic states, such as tuberculosis, typhoid and after intense slimming diets.¹⁶ Rare etiologies include human immunodeficiency virus positive patients receiving the protease inhibitor indinavir and chronic liver disease.^13,15 A case of idiopathic striae was also reported.¹⁷

Rosenthal¹⁸ proposed four aetiological mechanisms of striae formation: insufficient development of tegument, including elastic properties deficiency; rapid stretching of the skin; endocrinal changes; and other causes, possibly toxic.

Pathogenesis

The pathogenesis of striae is unknown but probably relates to changes in the components of extracellular matrix, including fibrillin, elastin and collagen.¹⁹ There has been emphasis on the effects of skin stretching in the pathogenesis of striae because the lesions are perpendicular to the direction of skin tension.²⁰ A possible role of glucocorticoids in the pathogenesis of striae has been suggested because of an increase in the levels of steroid hormones and other metabolites found in patients exhibiting striae.²¹ There are studies suggesting the role of fibroblasts in the pathogenesis of striae. Compared to normal fibroblasts, expression of fibronectin and both type I and type III procollagen were found to be significantly reduced in fibroblasts from striae, suggesting that there exists a fundamental aberration of fibroblast metabolism in striae distensae.²²

Pathological aspects

The earliest pathological changes are subclinical to be detected by electron microscopy only. These changes include mast cell degranulation and the presence of activated macrophages in association with mid-dermal elastolysis.²³ When the lesions become become clinically visible, collagen bundles start showing structural alterations, fibroblasts become prominent, and mast cells are absent.²³ On light microscopic examination, Inflammatory changes are conspicuous in the early stage, with dermal oedema and perivascular lymphocytic cuffing.²⁴ In later stages, there is epidermal atrophy, loss of rete ridges and other appendages including hair follicles are absent.²⁵

Evaluation of striae distensae

Approaches to evaluating SD severity visually include the Davey ²⁶ and Atwal scores,²⁷ although these have not been validated specifically for SD. An objective evaluation of SD may be carried out using skin topography, imaging devices including three-dimensional (3D) cameras, reflectance confocal microscopy and epiluminescence colorimetry.^28,29,30

Table 2: Visual scoring systems for the assessment of striae distensae

Management

Striae distensae (striae alba) is a very challenging cosmetic problem for dermatologists to treat. Various modalities of treatment have been tried. Although therapeutic strategies are numerous, there is no treatment which consistently improves the appearance of striae and is safe for all skin types.³¹ Weight loss by diet alone or a combination of diet and exercise do not change the degree of striae distensae.³²

Topical treatments

Topical tretinoin (0.1%) ameliorates striae and the improvement may persist for almost a year after discontinuation of therapy.³³ More recently, tretinoin has been shown to improve the clinical appearance of stretch marks during the active stage (striae rubra), although with not much effect during the mature stage (striae alba).³⁴ Some of the studies have proven the inefficacy of the vitamin A derivative in the treatment of SD, but most of the patients included in these early studies presented with old lesions that had evolved into whitish atrophic scars.³⁵ A study comparing topical 20% glycolic acid and 0.05% tretinoin versus 20% glycolic acid and 10% L-ascorbic acid, found that both regimens improved the appearance of striae alba.³⁶

Hydrant Creams: 1) Trofolastin (a cream containing Centella asiatica extract, vitamin E, and collagen-elastin hydrolysates). The exact mechanism of action was identified as the stimulation of fibroblastic activity ³⁷ and an antagonistic effect against glucocorticoids.³⁸ 2) Verum (a cream containing vitamin E, panthenol, hyaluronic acid, elastin and menthol). The results suggest that the product may show the benefit of massage alone.³⁹ 3) Alphastria (a cream composed of hyaluronic acid, allantoin, vitamin A, vitamin E, and dexpanthenol). Only one study was conducted, which concluded that the product markedly lowered the incidence of stretch mark development after pregnancy.⁴⁰

Glycolic acid (GA): The exact mechanism of action of GA in the management of striae distensae is still unknown because, although GA is reported to stimulate collagen production by fibroblasts and to increase their proliferation in vivo and in vitro, which may be useful for the treatment of stretch marks.^41,42 A study comparing topical 20% glycolic acid and 0.05% tretinoin versus 20% glycolic acid and 10% L-ascorbic acid, found that both regimens improved the appearance of striae alba.⁴³

Trichloroacetic acid (TCA; 10–35%): It has been used for many years as a treatment option for striae distensae and is repeated at monthly intervals with reported improvement in texture and color of marks.⁴⁴

Other topical products: Several oils have been used in the prevention of SD. A non-randomized, comparative study investigated the effect of almond oil in the prevention of SD in which they noted significant differences in the frequency of SD between the groups (almond oil and massage 20%, almond oil alone 38.8%, control 41.2%).⁴⁵

Overall, there is limited evidence for the efficacy of topical therapy for the treatment of SD.

Microdermabrasion

Microdermabrasion may improve many skin problems including acne scars, skin texture irregularities, mottled pigmentation and fine wrinkles. Karimipour et al reported that microdermabrasion induces epidermal signal transduction pathways associated with remodelling of the dermal matrix.⁴⁶ However, studies documenting the efficacy of rnicrodermabrasion in treatment of striae are lacking. Published in 1999, a book on microdermasion written by a French dermatologist, Francois Mahuzier, and translated to English, has a chapter "Microdermabrasion of stretch marks^”.⁴⁷ The author states that 10-20 sessions of microdermabrasion at an interval of not less than 1 month, each session resulting in bleeding points, provide satisfactory results. The author concludes that, "microdermabrasion is the only effective treatment of stretch marks today."

Lasers

Lasers have recently become a popular therapeutic alternative to ameliorate and improve the appearance of stretch marks. Most commonly used lasers used include pulsed-dye laser (PDL), short- pulse carbon dioxide and erbium-substituted yttrium aluminium garnet (YAG), neodymium- doped YAG (Nd:YAG), diode, and Fraxel.

Pulsed dye laser: The dilated blood vessels render the striae rubrae a good candidate for PDL.⁴⁸ The 585- nm pulsed dye laser has a moderate beneficial effect in the treatment of striae rubra.⁴⁹ To evaluate the effectiveness of the 585-nm flashlamp-pumped pulse dye laser in treating cutaneous striae, 39 striae were treated with four treatment protocols.⁵⁰ Subjectively, striae appeared to return toward the appearance of normal skin with all protocols. Objectively, shadow profilometry revealed that all treatment protocols reduced skin shadowing in striae. Laser treatment of SD should be avoided or used with great caution in darker skin types (IV–VI), because of the possibility of pigmentary alterations after treatment.⁵¹

Excimer laser: Studies have shown temporary repigmentation and improvement of leukoderma in SD with excimer laser, although it failed to show any improvement in skin atrophy.^52,53 To evaluate the true efficacy of the 308-nm excimer laser for darkening striae alba, 10 subjects were treated using the excimer laser on the white lines of striae, while the normal skin near to and between the lines was covered with zinc oxide cream. The results of this study showed the weakly positive effect of the 308-nm excimer laser in the repigmentation of striae alba.⁵⁴

Copper Bromide laser: copper-bromide laser (577-511 nm) has been used for stretch marks. A clinical study was conducted in 15 Italian women with stretch marks, treated with the CuBr laser (577-511 nm) and followed-up for 2 years.⁵⁵ The results of the study concluded that the copper-bromide laser was effective in decreasing the size of the SD and there were some pathogenic considerations that justified the use of this laser.

1,450-nm Diode Laser: The non-ablative 1,450-nm diode laser has been shown to improve atrophic scars and may be expected to improve striae. To evaluate the efficacy of the 1,450-nm diode laser in the treatment of striae rubra and striae alba in Asian patients with skin types 4-6, striae on one half of the body in 11 patients were treated with the 1,450-nm diode laser with cryogen cooling spray with the other half serving as a control.⁵⁶ None of the patients showed any noticeable improvement in the striae on the treated side compared to baseline and to the control areas. The study concluded that the non-ablative 1,450-nm diode laser is not useful in the treatment of striae in patients with skin types 4, 5, and 6.

1,064-nm Nd:YAG Laser: A study was aimed to verify the efficacy of this laser in the treatment of immature striae in which 20 patients with striae rubra were treated using the 1,064-nm long-pulsed Nd:YAG laser.⁵⁷ A higher number of patients (55%) considered the results excellent when compared to the same assessment made by the doctor (40%).

Intense Pulsed Light: In order to assess the efficacy of IPL in the treatment of striae distensae, a prospective study was carried out in 15 women, all of them having late stage striae distensae of the abdomen.⁵⁸ All the study subjects showed clinical and microscopical improvement after IPL. It seems to be a promising method of treatment for this common problem with minimal side-effects, a wide safety margin and no downtime.

Fractional Photothermolysis: To determine the efficacy of fractional photothermolysis in striae distensae, 22 women with striae distensae were treated with two sessions each of fractional photothermolysis at a pulse energy of 30 mJ, a density level of 6, and eight passes at intervals of 4 weeks and response to treatment was assessed by comparing pre- and post-treatment clinical photography and skin biopsy samples.⁵⁹ Six of the 22 patients (27%) showed good to excellent clinical improvement from baseline, whereas the other 16 (63%) showed various degrees of improvement. This study concluded that Fractional photothermolysis may be effective in treating striae distensae, without significant side effects.

Ablative 10,600-nm carbon dioxide fractitional laser: Ablative 10,600-nm carbon dioxide fractional laser systems (CO₂ FS) have been used successfully for the treatment of various types of scars. To assess the therapeutic efficacy of CO₂ FS for the treatment of striae distensae, 27 women with striae distensae were treated in a single session with a CO₂ FS and clinical improvement was assessed by comparing pre- and post-treatment clinical photographs and participant satisfaction rates.⁶⁰ The evaluation of clinical results 3 months after treatment showed that two of the 27 participants (7.4%) had grade clinical 4 improvement, 14 (51.9%) had grade 3 improvement, nine (33.3%) had grade 2 improvement, and two (7.4%) had grade 1 improvement. None of the participants showed worsening of their striae distensae.To assess and compare the efficacy and safety of nonablative fractional photothermolysis and ablative CO(2) fractional laser resurfacing in the treatment of striae distensae, 24 ethnic South Korean patients with varying degrees of atrophic striae alba in the abdomen were enrolled in a randomized blind split study and were treated with 1,550 nm fractional Er:Glass laser and ablative fractional CO(2) laser resurfacing.⁶¹ These results of the study support the use of nonablative fractional laser and ablative CO(2) fractional laser as effective and safe treatment modalities for striae distensae of Asian skin with neither treatment showing any greater clinical improvement than the other treatment.

UVB/UVA1 Combined Therapy: Besides lasers, light sources emitting ultraviolet B (UVB) irradiation have been shown to repigment striae distensae. A study was conducted on 9 patients with mature striae alba who received 10 treatment sessions, and biopsies were taken at the baseline and end of the study.⁶² At the end of the study, all patients reported some form of hyperpigmentation that was transient and did not affect any surrounding tissues. No changes were seen on biopsy to indicate an effective remodelling collagen effect of the device, although it needs further assessment. Another study was conducted to analyse the histologic and ultrastuctural changes seen after UVB laser- or light source-induced repigmentation of striae distensae in which analyses of biopsied skin after treatment with both the UVB laser and light source showed increased melanin content, hypertrophy of melanocytes, and an increase in the number of melanocytes in all patients.⁶³

Radiofrequency devices: RF devices are based on the principle of heat generation that occurs in response to poor electrical conductance according to Ohm’s law (heat generation is directly correlated with tissue resistance). The heat that is generated is sufficient to cause thermal damage to the surrounding connective tissue,⁶⁴ which is responsible for the partial denaturation of pre-existing elastic fibers and collagen bundles.⁶⁵ Initial collagen denaturation within thermally modified deep tissue is thought to represent the mechanism for immediate tissue contraction; subsequent neocollagenesis further tightens the dermal tissue and reduces striae.⁶⁶ The efficacy and safety of combination therapy with fractionated microneedle radiofrequency (RF) and fractional carbon dioxide (CO2) laser in the treatment of striae distensae has been evaluated revealing that this combination therapy is a safe treatment protocol with a positive therapeutic effect on striae distensae.⁶⁷ A recent study evaluating the effectiveness of a RF device in combination with PDL subjected 37 Asian patients with darker skin tone with SD to a baseline treatment with a RF device and PDL.⁶⁸ All histological evaluations demonstrated an increase in the amount of collagen fibers, and six of the nine specimens showed an increase in the number of elastic fibers.TriPollar RF device appears to be a promising alternative for the treatment of striae distensae in skin phototypes IV-V.⁶⁹

Needling therapy:

To evaluate the effectiveness and safety of a disk microneedle therapy system (DTS) in the treatment of striae distensae, 16 Korean volunteers with striae distensae alba or rubra were enrolled which received three treatments using a DTS at 4-week intervals.⁷⁰ Marked to excellent improvement was noted in seven (43.8%) patients, with minimal to moderate improvement in the remaining nine. This study revealed that Disk microneedle therapy system (DTS) can be effectively and safely used in the treatment of striae distensae without any significant side effects. Another study assessed and compared the efficacy and safety of needling therapy versus CO2 fractional laser in treatment of striae and the results supported the use of microneedle therapy over CO2 lasers for striae treatment.⁷¹

Platelet-rich plasma:

Platelet-rich plasma has these wound-healing properties, affecting endothelial cells, erythrocytes, and collagen,⁷² which potentially aids in the healing of the localized chronic inflammation believed to be a factor in the aetiology of striae distensae. Platelet-rich plasma is well tolerated by the patients and is a safe and cost effective treatment option for striae distensae.

Platelet-rich plasma alone is more effective than microdermabrasion alone in the treatment of striae distensae, but it is better to use the combination of both for more and rapid efficacy.⁷³

The plasma fractional radiofrequency and transepidermal delivery of platelet-rich plasma using ultrasound has also been found to be useful in the treatment of striae distensae.⁷⁴

Since thermal damage from intradermal RF has characteristics similar to those of many wounds, combination treatment with intradermal RF and autologous PRP would eventuate in enhanced localized collagen neogenesis and redistribution. In one of the studies, three sessions of intradermal RF were used combined with autologous PRP administered once every four weeks.⁷⁵ All of the participants showed satisfactory changes and no patient was reported to show no improvement.

Transepidermal retinoic acid:

Transepidermal retinoic acid delivery using ablative fractional radiofrequency associated with acoustic pressure ultrasound has also been used for the treatment of stretch marks.⁷⁶

Conclusion

Striae distensae are an extremely common, therapeutically challenging form of dermal scarring. Adequate scientific knowledge and the evidence behind both preventative and therapeutic agents are vital in order to understand striae and to offer patients the best therapeutic options. The treatment of this cosmetically distressing condition has been disappointing and there is no widely accepted surgical procedure for improving the appearance of stretch marks. Laser therapy has been advocated as a treatment for striae distensae.

INTRODUCTION

Hepatitis viruses are the most widespread cause of hepatitis and some cancer lymphomas in humans¹.Hepatitis is a serious disease of the liver and described as a lifelong infection with swelling and inflammation (presence of inflammatory cells) in the liver, that if progresses, may lead to cirrhosis (scarring) of the liver, liver cancer, liver failure, and death. Hepatitis B (HBV) and Hepatitis C (HCV) are one of the viral types of hepatitis that leads to jaundice (a yellow discolouration of skin, mucous membrane and conjunctiva of the eye), anorexia (poor appetite), fatigue and diarrhoea and presumably it remains undiagnosed and leads to chronic carrier state but most infected individuals remain asymptomatic^1-3. The hepatitis B virus is a DNA virus belonging to the Hepadnaviridae family of viruses and hepatitis C virus is a small, single stranded, RNA virus with a diameter of about 50 nm, belonging to Flaviviridae family of virus. Hepatitis B surface antigen (HBsAg) is present in the serum of those infected with hepatitis B, consisting of the surface coat lipoprotein of the hepatitis B virus. Anti-HCV antibody, a substance that the body makes to combat HCV ⁴. Hepatitis B virus is transmitted through blood and blood products, semen, vaginal fluids, and other body fluids. Hepatitis C virus is a blood borne or parenterally transmitted infection. Vehicles and routes of parenteral transmission include; contaminated blood and blood products, multi-transfusions (thalassemic and haemophilic patients), needle sharing, contaminated instruments (e.g. in haemodialysis, reuse of contaminated medical devices, tattooing devices, acupuncture needles, razors) and occupational and nosocomial exposure^5-8. It stands to reason that an occupational risk for transmission of hepatitis virus in the health care setting, where unknown carriers of hepatitis infections are undergoing different procedures, in which there is a chance of contact of percutaneous blood, including transmission from infected patients to staff, from patient to patient, and from infected providers to patients⁹. There is a lack of routine serological screening prior to surgery, which is one of the factors responsible for increased disease transmission. The major risk factors include; re-use of contaminated syringes, surgical instruments and improperly screened blood products². Without meticulous attention towards infection control and disinfection and sterilization procedures, the risk for transmission of blood borne pathogens in the health care setting is magnified.

The aim of our current study was to estimate the incidence of Hepatitis B and Hepatitis C among patients going through eye surgery at department of ophthalmology Liaquat University of Medical and Health Sciences Jamshoro at Hyderabad. This is one of the largest tertiary care centres in Sindh. This institution is a great referral centre for whole interior Sindh province.

MATERIAL AND METHODS

Study design and patients

This prospective observational study was carried out at Liaquat University Eye Hospital, Hyderabad, from June 2014 to February 2016. A total of 2200 patients undergoing eye surgery, who were unaware of hepatitis B & C infection were included in this study. No re­striction was placed based on age and gender to ensure maximum participation.

Blood samples

The blood samples of all these patients were collected in the Hospital laboratory, Scientific Ophthalmic Diagnosis & Research Lab. Each patient was serologically screened, by using immuno-chromatography (ICT method) for qualitative detection of antigen for Hepatitis B and Hepatitis C virus antibodies, to find the carrier status of patients before surgery.

The blood was collected by a qualified technician / phlebotomist of our hospital laboratory under supervision of a consultant pathologist. Samples were allowed to coagulate at room temperature for 30 minutes, and then centrifuged at 3000 revolutions per minute (RPM) for 10 minutes. The serum samples were separated and kept frozen at -20°C for chemical and immunoassays. The HBV screening was based on the detection of antigen and detection of viral specific antibodies HCV in the sera using enzyme immunoassays. The test only shows whether a person has ever been infected by HBV or HCV, and not whether the virus is still present. According to the manufacturers’ literature, the relative sensitivity and specificity of HCV and HBV testing kits was 96.8% and 99% respectively.

Those patients with test results were found positive on screening test, were further confirmed by testing ELISA (Enzyme-Linked Immunosorbent Assay) method (4th generation ELISA) and were given advised for further testing on Polymerase Chain Reaction (PCR) for qualitative or quantitative detection of DNA/RNA (the viral gene).

All the data was entered in SPSS version 16 and the prevalence and percentage of all variables was measured.

RESULTS

A total number of 2200 patients were operated during the study, 1255 (57.04%) patients were male and 945 (42.95%) were female

Of these 2200 patients, 338 (15.36%) were serologically positive for hepatitis B virus & hepatitis C virus. Out of the 338 HBV or HCV positive patients, 56 patients (2.54%) were positive for hepatitis B surface antigen (HBsAg) and 282 patients (12.81%) were positive for hepatitis C antibody (HCVAb). (Figure 1&2). The majority of them were female, and 226 (66.86%) were in their 4^th and 5^th decade of life in both sexes (Figure 3).

Figure 1- A: Serologically positive for hepatitis C antibodies, B: Serologically negative for hepatitis C antibodies

Figure 2 - A: Serologically negative for hepatitis B antigen, B: Serologically positive for hepatitis B antigen

Figure 3: Incidence of Hepatitis B & C in different age group

DISCUSSION

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are among the principal causes of liver diseases, with different frequency rates and various types all over the world. The World Health Organization (WHO) estimates that there are near 4 million people with chronic HBV infection and 170 million people with chronic HCV infection worldwide. Mortality rate of Hepatitis B is estimated to result in 563,000 deaths and hepatitis C in 366,000 deaths annually ^{1, 6, 10-12}. The occurrence of hepatitis varies from country to country. The epidemiological estimates by WHO show that there is low prevalence of hepatitis C (<1%) in Australia, Canada and Northern Europe, and almost 1% in countries of medium endemism, such as the USA and most of Europe. The frequency is at its peak (>2%) in many countries of Africa, Latin America, Central and South-East Asia ⁵. As far as the Pakistani population is concerned, the incidence of hepatitis B and C is escalating. Previous studies reveal that the Pakistani population affected by HBV 10% and HCV is 5-10% ³. At times it will also vary among different regions of the same country, and is continuing to rising in certain parts, especially in the rural areas, the percentage of infected individuals is significantly higher ². The total incidence of Hepatitis B and Hepatitis C in our study was found to be 15.36%. This was almost comparison to Naeem et al found to be 12.99% ² and in our previous study reported incidence of anti HCV was 29.60% ⁷. W Ul Huda et al reported 17.33% incidence of HCV infection among their operated patients⁵, whereas a study conducted by Khurrum et al reported 6% incidence of anti HCV antibodies in health care workers in a local hospital¹³. The prevalence of Hepatitis B and Hepatitis C in preoperative cataract patients was found to be higher in males (59.18%) than females (40.82%), and Ahmed et al also showed that the total prevalence of Hepatitis B and Hepatitis C in males was very high compared to females among preoperative cataract patients¹⁴, which is controversial to our result. A study conducted in 2010 on different eye camps in Pakistan showed that 108 out of 437 patients were infected with Hepatitis B and Hepatitis C with a higher prevalence of the diseases in females with 60.18% (65/ 108) than in males with 39.81% (43/108) ¹⁵. Concerning demographic variables, the increase in the risk for HCV seropositive incidences increased with the age i.e. 7.1% at the age of 20 to 30 years whereas 21.4% at the age of 40 to 50 years. In our study, the higher prevalence of hepatitis B & C were in the age range of 30 – 60 years, which is comparable to the study of Talpur et al, in which 65% positive patients were above the age of 40 years¹⁶.

This study shows that the prevalence of these hepatitis causing viral pathogens are quite high. Doctors and paramedical staff in surgical and medical practice are at high risk of acquiring blood borne diseases from the patients on whom they operate.

CONCLUSION

The aim of the present study was to assess the prevalence of HBV and HCV infection among preoperative patients. The incidence of these hepatitis causing viruses are higher in our population. Therefore, it is a mandatory task to screen every patient for hepatitis B and C before any surgical procedure. The surgeons and health care professionals should protect themselves by using protective masks, eye protection glasses, and double gloves before handling infected cases. The used infected material, needles and other waste material should be destroyed properly using Biosafety protocols.

INTRODUCTION

Like doctors in other specialties, general medical practitioners (GPs) are exposed daily to human suffering which most of society try to avoid.¹ The World Health Organisation (WHO) predicts that by 2030 depression will be ‘the leading cause of disease burden globally.’ And that 1 in 4 individuals seeking health care are ‘troubled by mental or behavioural disorders, not often correctly diagnosed and/or treated.’^{2, 3} Doctors suffer from stress, anxiety and depression (as well as vascular disease, cirrhosis of the liver and road traffic accidents) more than the general population.^4-10 Help for doctors is inadequate and doctors are reluctant to seek help.^{1, 4, 11} Where improvement is suggested, it is usually as counselling and general support.¹¹ Instead of ‘more of the same’, we suggest a radically different approach: Adaptation Practice, which Clive Sherlock pioneered and has taught since 1975. It is pragmatic and safe. This study tests its acceptability to a group of working doctors.

Doctors bear the responsibility for fellow human beings’ health, well-being and, often, for their very survival. Added to this, GPs are under increasing pressure from more patients who want more cures and from health service managers who demand clinical excellence and more administration and more managerial skills of them. GPs’ stress is related to increasing workloads, changes to meet requirements of external bodies, insufficient time to do the job justice, paperwork, long hours, dealing with problem patients, budget restraints, eroding of clinical autonomy, and interpersonal problems.^{6, 10, 12} The recent rise in the GMC’s Fitness to Practice complaints related to patients’ expectations of doctors is yet another stress making them feel threatened.¹³

Job satisfaction for GPs is at its lowest level since a major survey started ten years ago, while levels of stress are at their highest. In 2015 there had been a year on year increase in the number of GPs reporting a slight to strong likelihood of their leaving ‘direct patient care’ within five years, with 53% of those under 50 and 87% of those over 50.⁶

By nature and vocation, GPs want to help but too much pressure is unbearable and takes its toll. They work, not with numbers, data or profits, but with human suffering, which, inevitably, is an emotional burden because of compassion and because it makes them aware of their own vulnerabilities and mortality. ^{3, 14} When combined with heavy workloads and low morale, doctors themselves inevitably suffer emotionally and psychologically.^{7, 10, 14} At the same time they and others feel they should be invincible.^{1, 15-17} What professional help is available for them is inadequate.^{3, 4, 18, 19} Existing support services in the UK are underfunded and sporadic.⁴ Some are outsourced to counselling services, and some of these are by telephone. Doctors do not like to be counselled and are reluctant to use these services.^{4, 15, 17}

Doctors themselves are the mainstay for diagnosis and treatment of mental illnesses but are not adequately trained.^{3, 20} Mental illness is not well understood and conventional treatments are insufficient and often harmful. ^{15, 20-23} Consequently, doctors do not have the wherewithal to deal with the emotional and psychological problems they face every day in their patients and often in themselves, their colleagues and their families.^{4, 12, 18}

There is significant prejudice, stigmatisation and intolerance of mental ill health within the medical profession due to lack of understanding and fear.^{3, 4, 9, 15, 17, 20, 21, 22, 24} This not only affects how doctors treat their patients, it also exacerbates their own difficulties when they suffer with emotional and psychological problems themselves, and dissuades them from self-disclosure and from seeking professional help.^{3, 4, 8, 10, 18, 20, 25, 26} To succumb to stress, anxiety and depression is seen as being weak and inadequate as a person and in particular as a doctor. ^{3, 4, 15} Doctors think they should know the answers and should be able to cope.^{1, 4}

However, doctors are willing to learn work-related skills as this present study set out to show.¹¹ Adaptation Practice is training; not treatment or therapy. The course in this study was presented as a postgraduate programme for doctors to learn how to cope with stress, anxiety and depression.

METHOD

Recruitment

We asked by letter all 314 GPs registered in one UK urban and semi-rural Health Authority Area if they would be interested in a course of twelve fortnightly seminars to learn the basics of Adaptation Practice: a programme of self-discipline to cope with stress, anxiety and depression. Included, was the Hospital Anxiety and Depression Scale (HADS). Those who responded and whose HADS scores were ≥ 8 (the threshold for anxiety and depression) were invited to the course.

Stress, anxiety and depression

Anxiety and depression were assessed by the HADS and stress by a simple stress scale (SSS – see Table 1) one month before training started, immediately prior to training, at three months (mid-way through the training) and at six months (at the end of training).

Evaluation of Adaptation Practice

Half of those GPs who applied for the course were unable to attend because of prior commitments on the days planned for the course. These acted as a control group. Those who attended the course were the study group. All those who attended were also assessed in private by the authors immediately before and throughout the course. At the end of the course the doctors wrote anonymous self-assessments.

Training in Adaptation Practice

Those attending the course were taught not to express and suppress upsetting and disturbing emotion, not to distract their attention from it (including not to think about it and not to analyse it) and not to numb themselves to it with chemicals (alcohol, recreational drugs or prescribed medication). Instead, they learned how to engage with their moods and feelings physically, not cognitively, and how not to engage with thoughts about them. They were instructed to practise this six days a week with whatever they were doing, wherever they were. They were all offered unrestricted confidential telephone and e-mail support from the authors between training sessions and after the course had finished.

Statistical Analyses

The results are reported as means ± standard errors of the means. The scores were normally distributed and the data were analysed by analysis of variance with additional paired comparisons within periods, using the LSD method. Correlations were determined using Pearson’s correlation. The analyses were carried out using the statistical software programme SPSS 17.0 for Windows.

RESULTS

Recruitment

Of 314 registered GPs, 225 (72%) responded to our initial contact, and of these 152 (68%) said they would be interested in participating in the training course. Recruitment was restricted to those with HADS scores ≥ 8. Of the 225 who responded there were 71 (32%) for anxiety, 35 (16%) for depression, and 79 (35%) for both. 29 (13%) applied to attend the course. All were experienced GPs. 15 of these attended and 14 were not able to attend because of pre-existing commitments on the course dates. They asked for alternative dates but these were not available.

At the initial assessment (one month before the course started) there were significant correlations between the scores for anxiety and depression (P < 0.001), anxiety and stress (P < 0.001) and depression and stress (P < 0.001). At the second assessment immediately before the course started these correlations remained highly significant.

Effects of Adaptation Practice

All those who attended the course reported a subjective improvement in their abilities to cope with their own stress, anxiety and depression, and in their sense of well-being.

Anxiety

There were no significant differences between the control and study groups either one month before the start (P=0.949) or immediately before the first session (P=0.914). The anxiety scores in both groups remained greater than 8 at both assessments (Figure 1). At the mid-point of the course the mean score had fallen slightly in the study group (Figure 1) but the difference was not significant (P=0.652) By the end of the course the mean anxiety score in the study group was significantly lower (P=0.008) than that of the control group (Figure 1). The mean scores for anxiety decreased over the 4 assessments. This tendency was significant in the study group (P=0.002) but not in the control group (P=0.567).

Figure 1: The mean anxiety scores and standard errors of the means (SEM) for a control group and a study group of doctors with pre-existing signs of anxiety, assessed twice before, once during and once at the end of a six-month course in Adaptation Practice.

Depression

There were no significant differences between the control and the study groups either one month before the start (P=0.310) or immediately before the first session (P=0.880). The mean HADS scores for depression before training were all greater than 8 (Figure 2). At three months (the mid-point of the course) the difference between the mean scores in the two groups was not significant (P=0.631). At the end of the course the mean depression score in the study group was significantly lower (P=0.046) than the control group (Figure 2). The mean scores for depression decreased over the 4 assessments. This tendency was significant in the assessment group (P=0.003) but not in control group (P=0.689).

Figure 2: The mean depression scores and standard errors of the means (SEM) for a control group and a study group of doctors with pre-existing signs of depression, assessed twice before, once during and once at the end of a six-month course in Adaptation Practice.

Stress

There were no significant differences between the control group and the study group either one month before the course started (P=0.234) or immediately before it started (P=0.505). The stress scores were all greater than 8 (Figure 3). At three months (the mid-point of the course) the difference between the mean scores between the two groups was not significant (P=0.621). At the end of the course the mean stress score in the study group was lower (P=0.077) than that of the control group (Figure 3). The mean assessment scores for stress decreased over the 4 assessments. This decrease was significant for the assessment group (P=0.001) but not for the control group (P=0.425).

Figure 3: The mean stress scores and standard errors of the means (SEM) for a control group and a study group of doctors with pre-existing signs of stress, assessed twice before, once during and once at the end of a six-month course in Adaptation Practice.

Correlations

At all four assessments there were correlations among all three psychological parameters. At the initial assessment the correlation between anxiety and depression (r2= 0.405; P = 0.029) and between depression and stress (r2= 0.800; P < 0.0001) were significant but the correlation between anxiety and stress was not (r2= 0.253; P = 0.185). At the commencement of the course the correlation between anxiety and depression (r2= 0.479; P = 0.009), between depression and stress (r2= 0.765; P < 0.0001) and between anxiety and stress (r2= 0.486; P = 0.007) were all significant.

At three months (the mid-point) the correlation between anxiety and depression (r2= 0.526; P = 0.003), between depression and stress (r2= 0.622; P < 0.0001) and between anxiety and stress (r2= 0.790; P < 0.0001) were all significant and similarly at the and of the course: the correlation between anxiety and depression (r2= 0.604; P = 0.001), between depression and stress (r2= 0.577; P =0.001) and between anxiety and stress (r2= 0.740; P < 0.0001) were also all significant.

Assessments of the doctors’ psychological states and methods of coping

The doctors attending the course were assessed individually in private. They variously complained of stress, anxiety and depression. Notable findings included suicidal thoughts, plans for suicide, self-medication, excessive consumption of alcohol and an intention to leave the medical profession because of the unbearable pressures involved.

By the end of the course all these signs and symptoms had improved and the doctors felt confident in their ability to cope not only with pressures from outside but also with emotion, moods and feelings inside. One doctor still wanted to leave the profession but less adamantly than before, and stayed.

There was no qualitative assessment of the control group.

Qualitative Self-assessments

The anonymous self-assessment reports give meaningful, subjective accounts of what the doctors experienced individually. They fall into four main themes. There were no negative comments.

Connecting with emotion physically in the body

The following comments indicate contact with emotion:

‘I am more aware of my feelings.’

‘It is difficult to say “Yes” to unpleasant or upsetting feelings and situations. I have always preferred to avoid them and I have had a lifetime of suppressing emotions, so it is very difficult to say “Yes” to them, but this is what I am now doing.’

‘Since I’ve been more aware of my feelings there has been an enormous improvement in concentration.’

Developing inner emotional strength and coping.

A number of comments indicate the need to develop the strength to contain emotion physically in the body:

‘I am more accepting of daily stresses at work.’

‘I try to deal with problems instead of feeling so desperate and so wronged by them.’

‘I am calmer, and I lose my temper less often and less dramatically.’

‘The Practice was difficult initially because of my own resistances to it.’

‘I’ve always avoided seeking help for myself. I often feel worse than the patients I prescribe antidepressants for. I can now cope and I feel stronger but I don’t feel I’ve been treated and I now realise I didn’t need treatment: I needed to learn what to do and how to do it.’

Dealing with unpleasant, unwanted thoughts.

These comments illustrate the doctors’ new reactions to thoughts as they started to address the underlying emotion that normally drives worrying thoughts:

‘I now have less ruminations.’

‘As a long-standing ruminator I now realise these thoughts are the source of many anxieties. Thoughts were the main problem for me.’

‘I have learned to deal with obsessional thoughts by not giving time to them.’

General well-being.

The doctors commented on their sense of general well-being and ability to cope:

‘I am less tense and less anxious.’

‘I am now coping with episodes of work overload much better.’

‘I am feeling better generally.’

‘This has given me confidence to pursue the course of action I knew was correct.’

‘There are all-round improvements because of adapting myself to work and other people.’

‘I am happier and more content, optimistic and much less negative.’

DISCUSSION

Varying degrees of stress, anxiety or depression are universal.^{16, 26} Only about half of those thought to be clinically affected by these conditions seek help for them.²⁶ If put into practice, sound medical knowledge and training can be beneficial to doctors’ own health.^{1, 11, 15} This does not seem to be true for stress, anxiety and depression.²² Too little is known about emotional and psychological problems, and treatment for them is inadequate.^{2, 9, 15, 17, 19, 21, 23, 28, 29}

In this study, there was a high level of interest in how to deal with stress, anxiety and depression. Almost one third of respondents had scores on the HADS and SSS that suggested worrying levels of emotional and psychological problems amongst these working GPs. The fact that 152 doctors (68% of respondents) declared an interest in a six-month evening course (90 minute sessions after work on Thursday evenings) to learn how to deal with these conditions, suggests that:

• stress, anxiety and depression are significant problems either amongst their patients or for the GPs themselves, or both
• GPs are not confident in their ability to deal with them and want to learn more
• although they have a strong tendency not to admit that they cannot cope and not to seek help, doctors are willing to attend a course to train and to learn.¹¹

Most doctors tell their patients to seek professional help and to talk about their feelings but do not do so themselves.^{3, 5} They prescribe drugs for their patients that either the doctors will not take themselves or that they take but find ineffective. Of the 15 GPs on the course only one had mentioned psychological difficulties to a colleague and one to a partner and both only reticently. ¹⁶

ADAPTATION PRACTICE

Adaptation Practice strongly discourages self-disclosure, except in private to the Adaptation Practice teacher, which is necessary in order to assess the nature and severity of any problems and to lay the foundations for a rapport. Adaptation Practice sessions involve detailed discussion of moods and feelings as physical sensations and powerful forces that affect behaviour in all human beings. The ethos in Adaptation Practice is for participants to learn from their own experience how they are affected by emotion and how they can change this by containing themselves and not letting the emotion control them. It is not to criticise, judge, blame or condemn. Consequently, without the causes of stigmatisation, there is no prejudice and no stigma; instead there is respect and dignity and a pragmatic attitude to change.¹⁶

Adaptation Practice trains individuals to bear and endure upsetting, disturbing emotion by not expressing it, not suppressing it, not distracting themselves from it and not numbing themselves to it with drugs (alcohol, recreational drugs or prescribed medication). Bearing it this way develops emotional strength and resilience.

The high level of interest, the willingness to attend in groups and the positive results from this study indicate that Adaptation Practice is an acceptable way of teaching doctors how to cope with their own stress, anxiety and depression, that makes sense intellectually and emotionally. This, as well as the pragmatic approach mentioned above, makes Adaptation Practice radically different from other approaches.

GENERAL COMMENTS

Given that those who could not attend asked for an alternative day to attend, gave us reason to assume that the manner in which the study group and the control group were selected – individual availability on a given week night – would not have biased the sampling procedures and it seems reasonable to assume that the two groups did not differ in any meaningful way that would have biased the outcome.

Not surprisingly, there were strong positive correlations between anxiety and depression and between depression and stress on all assessments and between anxiety and stress on all but the first assessment, suggesting a strong association among these parameters of psychological states.

The mean scores for anxiety, depression and stress fell significantly in the participating GPs compared with the control group. The subjective reports from both the medical assessments and the self-assessments support these changes in the study group.

This study begs a number of important questions:

• if doctors are prejudiced and stigmatise mental illness amongst themselves then what are their conscious, or unconscious, attitudes to mental illness in their patients? ^{3, 5, 9, 24}
• if doctors cannot cope with emotional problems themselves then whom are they and their patients to turn to for help? This is not the same as doctors suffering from physical conditions requiring surgery, or medications such as insulin or antibiotics.^{3, 5} Doctors expect, and are expected, to be able to cope with their emotions and, if necessary, that the treatment they give their patients will also work effectively for themselves
• what are doctors to do and what are their patients to do, when doctors succumb to their own moods and feelings?

Adaptation Practice could be integrated in the medical curriculum at undergraduate and postgraduate levels, including Continuing Professional Development (CPD). Not only GPs but all doctors and other healthcare staff (nurses, physiotherapists, occupational therapists, social workers, etc.) could develop emotional resilience – which the GMC have proposed in recent years – and a better understanding of emotional and psychological problems and mental illnesses.

It is hoped that this preliminary study will stimulate and encourage a new way of looking at and investigating emotional and psychological problems and lead to further evaluation of Adaptation Practice.^{29, 30}

With adequate training doctors and psychologists could teach Adaptation Practice.

Schizophrenia sufferers feel like abstract entities with non-animated bodies, often experiencing auditory verbal hallucinations (AVH) due to morbid “objectification” of inner dialogue.¹ From the patient’s perspective, AVHs are a subjective–objective phenomenon. AVH is a non-consensual, dynamic and psychologically charged experience and the voices often echo significant emotions. Derogatory voices are common representations of unconscious self-hatred that cannot stand up to the external world’s logic. Thus, patients need help to incorporate it. Auditory hallucinations may be arising because of an interaction between biological predisposition, perceptual and cognitive factors. According to an integrated model of auditory hallucination (AHs) suggested by Waters et al,² AHs arise from an interaction between abnormal neural activation patterns that generate salient auditory signals and top-down mechanisms that include signal detection errors, executive and inhibition deficits, a tapestry of expectations and memories. Recently, neuro-quantologists have proposed that AVHs may be an objectification of parallel thinking/quantum thinking.³ Parallel thinking is a source for thought insertion. There may be different variables of AVHs. Experiencing AVH has serious impact on the quality of life of the affected individual, and is a significant factor in prevalence of suicides among schizophrenic patients.⁴

Incidence

One in four schizophrenia sufferers experiences persistent AVH .⁵ AVHs are experienced by approximately 53% of schizophrenia sufferers ⁶ and are present in 28% of major affective disorders (Goodwin& Jamison, . ⁷ Evidence indicates that each patient responds differently to the voices, according to his/her evaluation of them (Table 1), which influences the degree of interventions. Specific dimensions of AVHs can give hints to the future likelihood of treatment resistance. Although the percentages differ in various studies, it is assumed that about 30% of patients have command hallucinations and they are seen as the ultimate betrayal of the mind. ⁸ Often, the content of such messages is negative; thus, commanding AVHs are more distressing than commenting ones. Schizophrenia predisposes them to a greater risk of suicides and homicides. Command hallucinations are more prevalent among forensic patients and contribute to their forensic status.

Table1. Patients’ Response to AVH

The multi-factorial polygenic model of schizophrenic disorders has received great support and signifies that genetic factors play a bigger role than environmental factors in familial transmission of these disorders. Relevant studies provide little support for the mechanism of single major locus inheritance. A mechanism involving two, three, or four loci cannot be ruled out even though there is no compelling support for such models.⁹ It has also been proposed that a single gene may be even responsible for hallucinatory experiences ¹⁰ implying that those who have not inherited such a gene may not experience auditory hallucinations, but still could experience other characteristic symptoms of schizophrenia. One may also hypothesise that an individual who has inherited such a “hallucinatory gene” but not all the schizophrenia genes could hear non-clinical voices without having other schizophrenic symptoms. It is also arguable that those who carry such a specific gene are more vulnerable to experience hallucinations when they abuse psychoactive substances and could get misdiagnosed as having schizophrenia, but hallucinations may cease to occur once they abstain from illicit drug abuse.

Measurements for Assessment

AVH is a subjective experience and is hard to measure objectively. Several rating scales are now available for an efficient evaluation of different aspects of voice activities. Some are general and a number of them are specifically designed. Using rating scales facilitates better engagement with patients and helps in reinforcing the message that patients and the distress they experience are carefully considered.

Beliefs About Voice Questions (BAVQ) is an assessment scale useful in measuring the key beliefs about the voices.¹¹ It is typically used in conjunction with the Cognitive Assessment Schedule (CAS).¹² Voice Compliance Scale (VCS) is an observer rated scale aimed exclusively at measuring the frequency of command hallucinations and the level of obedience or confrontation with each recognized command.¹³ Voice Power Differential Scale (VPD) is another measure that can be applied to rate the perceived relative power differential between the voice and voice experience. ¹⁴ On the other hand, Omniscience Scale (OS) is intended to quantify the voice hearer’s beliefs about their voices’ knowledge regarding the bio data. ¹⁵ Another measure presently in use is Risk of Acting on Commands Scale (RACS), designed to assess the level of risk of acting on commands and the amount of associated distress. ¹⁶

The Bonn Scale (BSABS) is used for the assessment of basic symptoms, ¹⁷while the Schizophrenia Proneness Instrument (SPI-A) ¹⁸and the Examination of Anomalous Self Experience (EASE) ¹⁹ are useful aids in identifying minimal changes in subjective experience and for longitudinal monitoring (Table 2). In the extensively used Positive and Negative Syndrome Scale (PANSS), the hallucination item is one of seven in the positive subscale, which also includes delusions, conceptual disorganization, excitement, grandiosity, suspiciousness, and hostility. Given such a great number of scales in use, there is an obvious risk that differential anti-hallucinatory efficacy among antipsychotic drugs may be obscured by means of sum scores for the whole sample in clinical trials.

Table 2. Measurement scales

Treatments

Although many forms of treatments aiming to eliminate AVH or improve quality of life are available, use of medication seems to be the most prevalent. Besides drug treatment, non-invasive physical treatments, such as TMS and different forms of psychological interventions, have recently evolved. Drug therapies are aimed at symptom eradication, whereas psychological therapies tend to foster healing, recovery and personal growth. Rather than being specifically anti-hallucinatory, typically, neuroleptics offer a generalised calming effect and patients are given some “breathing space” to work through their voices. Usage of non-pharmacological tools is needed in the long-term management of refractory cases. Presently, intervention strategies for AVH are based on different models of hallucinations, but regrettably no clear models have been established.

Pharmacotherapy

The current understanding of AVH and the neural mechanisms involved is limited, and knowledge on how CNS drugs, such as antipsychotics, influence the subjective experience and neurophysiology of hallucinations is inadequate. Consequently, using pharmacotherapy in the management of AVH remains very challenging. ²⁰ Despite multiple trials of different combination and adjunctive therapies to an antipsychotic regime, AVH can remain drug resistant. It is also important to note that all antipsychotics are potentially anti-hallucinatory, even though these effects are usually modest. Moreover, given that, even when medications are effective, concordance can be an issue, antipsychotics should be used prudently and weighed up against effectiveness and side effects (Table 3). There are no clear guidelines for the drug treatment of AVH and comparisons of the efficacy of antipsychotics for AVHs are few. Clinical drug trials very rarely focus on single symptom scores, such as hallucinations, and tend to report group mean changes of overall psychopathology, or at best the positive subscale scores.

Evidences show that AVHs persist in spite of treatment in 32% of chronic patients ²¹ and 56% of acutely ill patients.²² Trifluperazine was popular as an anti-hallucinatory drug before the advent of atypical antipsychotic drugs. Clozapine is currently favoured for intractable AVHs and is beneficial in 30–60% of unresponsive patients.

Antipsychotic co-treatment is an option for clozapine augmentation. Olanzapine and risperidone may be alternative drugs in first episode psychosis. However, it is being debated whether clozapine should be used in such cases.

Table 3. Drug Treatment

Clozapine

Use of clozapine is suggested only after two other antipsychotics have been tried. It works better with continued usage and clinicians have to be patient in its upward titration. At six months, improvement in Global Assessment of Functioning score is significantly higher for clozapine in comparison to other antipsychotic drugs.²³ However, when prescribing clozapine, cautions and contraindications must be noted (Table 4).

While higher doses of clozapine may not have more anti-hallucinatory effect, they still carry the risk of inducing the potential side-effects of this highly efficacious drug (Table 5). The most dreaded haematological side-effects are usually manifested within six months. For that reason, during clozapine therapy, patient has to be closely monitored, bearing in mind its limitations in achieving the anti-hallucinatory effects. If higher doses do not have the desired effect, clozapine dose should be titrated downwards to a point of its maximum anti-hallucinatory effect in a particular patient. Such an endeavour can prevent the emergence of serious side-effects, resulting in a complete failure of the therapy. The dose can also be adjusted to a safer level in cases where the psychological interventions are found to be successful. Clozapine can be effective even in lower doses, such as 200 mg/day. Only in the presence of command hallucinations, higher doses should be prescribed to patients whose other positive symptoms are well under control.

Prophylaxis with an antiepileptic drugs, such as lamotrigine or sodium valproate, or similar should be commenced before titrating the dose above 600 mg daily. Close monitoring and active treatment of metabolic dysregulation should be initiated concurrent with clozapine therapy. In clozapine therapy, weighing up safety and superior antipsychotic efficacy and educating the patients on “clozapine lifestyle” is immensely important, as it helps in treating refractory cases of AVH. Thirty percent of patients treated with clozapine may remain unresponsive and clinicians have to lower their expectations to the level of achievement without being cynical. Isolated cases of clozapine-induced joint visual and auditory hallucinations have been reported. ²⁴ In spite of Clozaril treatment having the highest anti-hallucinatory effect, a good percentage of AVH sufferers remain symptomatic and are classed as super-refractory.⁸ According to Gonzales (2006), ²⁵ 50% of patients receiving antipsychotics achieve full remission, while 25% hear voices occasionally and 25% are unresponsive.

Table 4. Cautions & Contraindications of Clozapine

Table 5. Benefits and risks of Clozapine

Benzodiazepines are often abused by voice hearers aiming to reduce their anxiety. Such patients might benefit by the addition of antidepressant, as this could enhance their mental resources to cope with the voices, even though they have no anti-hallucinatory effects per se. Mood stabilisers are sometimes used to augment the efficacy of antipsychotics without any clinical validation. Despite multiple trials of different adjuvant therapies to an antipsychotic regimen, there have been few promising results. Still, in practice, clinicians may get frustrated, as they struggle to provide symptomatic relief to the voice hearers at any cost. Recently allopurinol, an anti-gout agent has been used as an adjunctive therapy and based on three randomized controlled trials, the result has been encouraging. ²⁶

Psychological Interventions

Persistent AVHs alone may not warrant pointless alteration of medication, as non-pharmacological interventions may achieve some control. When clinicians are not cognizant of non-pharmacological therapies, AVH patients that do not respond to antipsychotics alone may be mislabelled as having refractory AVH. In fact, they are only unresponsive to drug treatment, and could potentially respond to an integrated approach. Similarly, patients with treatment-refractory AVH are often over-diagnosed as suffering from hard to treat schizophrenia, even when other positive symptoms have been ameliorated.

There exists a false dichotomy between physical and psychological treatment approaches to AVH. In practice, both treatment modalities have to be modified in a personalised form. After all, psychiatry was originally known as psychological medicine. Presently, even though different forms of non-pharmacological interventions are available for drug-resistant AVH, some have questionable effects. ^27,28,29 (Table 6).

Table 6. Psychological Interventions

CBT therapists predicate that AVHs are a manifestation of the morbid objectification of inner dialogue (thinking in words),and accordingly verbalised thoughts are the raw material for AVHs.Verbal thinking differs from external speech in many respects and has several distinct features. CBT therapists believe that cognitive dysfunctions underlie AVH and they target them with cognitive remediation strategies. Those experiencing voices commonly think that they are caused by a powerful external agency, and are controlling and potentially harmful. Psychological factors, such as meta-cognitive biases, beliefs, and attributions concerning the origins and intent of voices, also play critical modulatory role in shaping the experience of AVH. Teaching patients to recognize the source of the voices alone has yielded beneficial effects.

Specific techniques have been designed to modify the frequency of AVHs and restore a sense of control over them. Earlier methods involved behavioural approaches based upon addressing hypothesized antecedents and reinforcers of voices and explored a variety of specific interventions such as relaxation training, graded exposure to voice triggers, manipulation of environmental possibilities and even aversion therapy. ³⁰ These behavioural techniques were eventually expanded on by the application of cognitive methods. The primary aim of psychological therapy is to change the belief that voices are omnipotent and uncontrollable and to suppress the associated attributes of false identity, wrong intentions, and urges to harm oneself and others. They encourage patients to challenge irrational interpretations and modify maladaptive behaviour, diverting attention from voices with distraction techniques (Table 7).

Reality testing and behavioural experiments are one form of CBT intervention, based on the view that behavioural changes can prompt cognitive changes. Attention switching can also be used to challenge the belief that hallucinations are uncontrollable. Command AVHs are more prevalent among the forensic population and are more distressing than the commenting ones. The risk of the sufferer acting on them is high when voices are perceived as omnipotent and uncontrollable. CBT has been proven beneficial in tackling command hallucinations. Lack of insight and formal thought disorder may not necessarily disqualify CBT for AVH; nonetheless, negative symptoms may pose a barrier to this form of psychological intervention. The current model of CBT for psychosis has been criticized, suggesting that it is simply an extension of general CBT concepts without taking into account the specificities of psychosis. ³¹ Patients with higher intelligence, who have the ability to grasp abstract concepts, might gain greater benefits from CBT. ³²

Table 7. Goals of CBT

Combining psycho-education and supportive psychotherapy has been found to enhance the functioning and self-esteem of voice hearers, providing a therapeutic structure. In the increasingly popular self-help voice-hearing groups, the ethos of recovery is understanding, accepting and integrating the sufferer’s turmoil. Acceptance and non-judgemental support of people with similar experiences has helped many patients cope with the condition. In response, the number of books on AVH, aiming to educate the sufferers and carers, has grown considerably.

Newer Psychological Interventions

Attention Training Technique (ATT) focuses on negating psychological distress through cognitive and meta-cognitive modification. ^33,34 Patients focus on up to five neutral sounds, such as a dripping tap, before switching their attention between different sounds. They then practise listening to all the sounds simultaneously. After a few weeks, they focus on neutral sounds and then on the AVH. Once this process is mastered, they switch attention between voices and other sounds, before being asked to divide their attention among them. This exercise continues for several weeks, whereby the aim is to replace the self-regulatory process with new processing configurations.

Acceptance and commitment therapy (ACT) is aimed at achieving psychological flexibility. It incorporates mindfulness and acceptance, considering AVH as a private experience and asserting that patients experience distress only when they try to deafen the voices. . By reducing struggle with voices and engagement with them, key responses such as arousal, attention and activation of brain areas are hypothesised to be reduced. ³⁵ The ideas behind ACT are consistent with the emphasis on the recovery movement of finding a way to live a valued life despite the ongoing problems. To this effect, unique and effective coping strategies are offered, whereby patients are given the insights that parts of the self are behind the voices. Thus, accepting them means sending a loving message of compassion, acceptance and respect to oneself Two randomised control studies have yielded promising results. ^36,37ACT follows a set manualised structure, rather than relying upon the complex and lengthy process of belief modification: therapy can be much briefer and potentially practiced by a wider range of clinicians and cost effective. ³⁸

There are verbal and non-verbal routes to emotions. As CBT uses the former in voice therapy, it is less effective when patients are negatively involved with the voices. On the other hand, Competitive Memory Training (COMET) uses the non-verbal route. Generally COMET sessions involve four stages.³⁹ A. identification of aspects of negative self-esteem reinforced by the voice; B. retrieval and re-living of memories associated with positive self-esteem; C. positive self-esteem is brought to compete with the content of the voices to weaken associations between voice content and negative self-valuation; and D. learning to disengage from the voices and to accept the voices as psychic phenomenon.

The significant past comes back to the conscious mind in AVH, as life experiences charged with emotion make a compelling impression on the brain. The observation that voices are knowledgeable about patients suggests that auditory hallucinations are linked to memory. In other words, negative experiences from memories evoke emotions, which should be deactivated. Distancing and decentring techniques could help patients to interpret voices as false mental events. As a result, incompatible memories could become tools to modify the power of voices—they are deactivated by new learning. Thus, when voices torment hearers, telling them that they are failures, a competing memory of such success as passing a significant examination is introduced. Posture, facial expression, imagination, self-verbalisation and music are all procedures included in the COMET protocol.⁴⁰

Compassionate mind training (CMT) is used to encourage better resilience to unpleasant commenting voices.CMT involves practicing exercises which promote self-compassion and compassion towards others. It is targeted to activate brain systems involved in social and self-soothing that amend threat systems active when experiencing unfriendly voices. ⁴¹

Mindfulness is paying attention in a particular way – on purpose, in the present moment and non-judgementally. Clinical literature cautions against use of meditation in psychosis, but the effectiveness of mindfulness-based approaches for people with psychosis has been demonstrated in controlled clinical settings. ⁴²and in the community. ⁴³ Abba et al. ⁴⁴ argue that effectiveness of mindfulness is a three-stage process: a. Becoming knowledgeable and developing more awareness of psychotic experiences and observing the thoughts and emotions that follow them. B. Permitting psychosis to come and go without reacting in order to cultivate understanding that distress is produced by the meanings one attaches to thoughts and sensations. C. Becoming autonomous by accepting psychosis and the self by acknowledging that the sensations only form part of the experience, and are not a definition of the self.

Neuroimaging studies are beginning to explain the neural mechanisms of how mindfulness might be working clinically. Structural changes have been observed in the anterior cingulate cortex, which is an area of the brain associated with emotional regulation. ⁴⁵ . There is evidence to suggest that mindfulness practice is correlated to reduced brain activity in the default mode network. ⁴⁶

Limited improvements with mono-therapy have prompted the development of multi-modular approaches. Hallucination-focused Integrative Therapy (HIT) is geared towards integrating CBT with neuroleptics, coping strategies, psycho-education, motivational intervention, rehabilitation and family treatment.⁴⁷ Extant studies indicate that integrated treatment is more effective than TAU (treatment as usual).

The continuum model of psychosis and ordinary mental events has incited the development of normalisation of the voice hearing experience.⁴⁸ Most psychiatric symptoms occur in normal people—just as breathlessness and palpitations occur while exercising—but are potential clinical symptoms. It is the frequency and duration that determine the borderline. According to the cognitive model, an internal mental event receives external attribution. Through normalisation, the external attribution can be reversed.

Although drug treatment may be the most practical way of managing AVH, refractory cases pose formidable challenges and it must be emphasized that psychological treatments are not counterproductive if applied skilfully. Clinicians who espouse the view that psychosis is a medical condition dismiss the usefulness of psychological interventions. The counter argument would be that a patient with a medical condition, such as stroke, benefits from physiotherapy, occupational therapy and psychological approaches.⁴⁹

Repetitive Trans-cranial Magnetic Stimulation

There are several ongoing trials in which the aim is to treat refractory AVH (Table 4). Repetitive transcranial magnetic stimulation (rTMS) is thought to alter neural activity over language cortical areas. Several studies on rTMS have shown improvement in the frequency and severity of AVHs, albeit without offering any strong conclusive evidence for its efficacy .⁵⁰ Moderate rates of AVH attenuation following rTMS have been noted in three meta analyses. Given that remarkable improvements in isolated cases have also been claimed, this suggests that rTMS may be appropriate mode of therapy for some patients.

Available data suggest that .rTMS selectively alters neurobiological factors that determine the frequency of AVH. However, a recent meta-analysis indicated that the effect of rTMS may be short-lived (less than one month).⁵¹ Studies seem to indicate that rTMS may be effective in reducing the frequency of AVHs, with little effect on their other topographical aspects.^50,52 Sham stimulation has also led to improvements in a number of AVH parameters. Compared to bilateral stimulation, rTMS of left tempero-parietal region appears more effective in reducing the AVH frequency . ⁵³ To reduce the distress associated with AVH and help patients to cope with hallucinatory predilection, rTMS could be combined with CBT. The side-effect profile is much cleaner for this biological approach when compared to medications. Still, like any other anti-hallucinatory treatments, neuro-stimulation technique does not guarantee long-term elimination of AVH. Electroconvulsive therapy (ECT) is considered a last resort for treatment resistant psychosis. Although several studies showed clinical improvement, a specific reduction in hallucinations severity has never been demonstrated.

Avatar Therapy

Computer-assisted voice therapy is a budding form of computerised psychological treatment that is currently undergoing trials.²⁸ In this novel therapy, persecutory voices are directly depowered with the aid of a computerised dummy of the alleged persecutor through voice dialogue. Analytically-oriented therapists can even converse with “voices” and such committed clinicians will find computerised voice therapy as another helpful tool. It is hard to ascertain whether the benefits of the avatar therapy were due to the specific technique involved or simply the increased attention and care, and Leff’s team acknowledged the limitations of their work.⁵⁴

Sound Therapy

Another important development in voice therapy is the use of tinnitus control instrument (TCI)—a form of sound therapy—in treating refractory AVH. Similar to AVH, subjective tinnitus is defined as the false perception of sound in the absence of acoustic stimuli. Even though their definitions are similar, the origin and underlying causes of these two conditions differ. Tinnitus is characterised by a simple sound—a monotone—and is non-verbal. In tinnitus, the brain is believed to interpret an internally generated electromagnetic signal as an acoustic sound or sounds.

Kaneko, Oda, and Goto²⁹ reported successful intervention in two cases of refractory AVH with sound therapy, using tinnitus control instrument (TCI) alongside antipsychotic medications. They posited that, in sound therapy, the auditory system is directly helping the limbic nervous system and the neuro-mechanism for AVH is sensitive to sound therapy .⁵⁵ They concluded that low-level auditory stimulation might be hindering the progression of voices and brain might be getting a breathing space to initiate self-healing process.

Future Directions

Hallucinogenic drugs, anti-hallucination medications and neuroimaging studies may lead to a better understanding of AVH. Animal models of hallucinations and pharmacogenetics might help to find more efficacious anti-hallucinatory drugs. AVHs themselves may have a genetic origin.¹⁰ Thus, not all patients that develop schizophrenia would experience AVHs. Such a finding might help shed more light on the genetics-linked mechanism and remedial measures of hallucinations in schizophrenia. Because the biological substrates facilitating drug effects on hallucinations remain largely unidentified, future studies with translational designs should address this important issue to find a more targeted drug treatment of psychosis.⁵⁶

If a derivative of clozapine without the haematological side-effects is formulated in the future, it might be an important milestone in the treatment of refractory AVHs and schizophrenia because clozapine has the most potent anti-hallucinatory effect. Such a novel drug could become the first line of treatment for schizophrenia, as it would address many of schizophrenic symptoms at their onset. This is crucial, as symptoms and habits become stronger and more resistant the more frequently they occur. Fatty acid amide derivatives of clozapine, such as DHA-clozapine, are found to have better pharmacological properties and enhanced safety. However, such claims are awaiting substantiation in clinical trials.⁵⁷ Thus, more attention needs to be directed into this potentially rewarding research arena. It is, however, very likely that, even after a better pharmacological cure is found for AVHs, a few symptoms might linger on for long periods. With this view, efficient non-pharmacological remedies have to be designed to deal with such residual symptoms.

Discussion

Medications help reduce the psychic pain, and protect the dignity of patients, as well as prevent suicides and homicides. From the patient’s perspective, the calming and relaxing effects of pharmacological therapies are a priority for relief from the distress due to AVH. Among the antipsychotics, clozapine has the maximum anti-hallucinatory effect and it is a shame that it cannot be used as a first line treatment choice. Treatment of AVH should be individualistic and clinicians should be prepared to apply several clinical and non-clinical approaches in concert to address them.

More research into the aetiology and mechanism of AVH is warranted in order to find effective treatment strategies. There is no shortage of theories about the mechanism of AVH, but there is no consensus among the investigators. It is unlikely that AVH is a pure neuro-chemical experience or a biological glitch, and this is where the currently available drug treatments fail. The distinction between primary and secondary symptoms was lost with the triumph of biological psychiatry in the last century. Thus, some authors presently claim that AVHs may even be a secondary symptom or a neuroquantological manifestation of an underlying biological disorder. We should not minimise the importance of eliminating symptoms when such symptoms are incapacitating, as in the case of hallucinatory experiences.

The present recovery model that emphasises and supports the patient’s potential for recovery involving hope, supportive relationship, empowerment, social inclusion, coping skills and meaning cannot be achieved without the help of psychological interventions. In this respect, CBT is a useful tool in the rehabilitation of psychotic patients with residual AVH. Jauhar et al.⁵⁸ argued that the effectiveness of CBT in schizophrenia is influenced by failure to consider sources of bias. Consequently, the benefits are more apparent than real, prompting the question of whether CBT has been oversold.⁴⁹ The verdict of Maudsley debate on the issue has been that CBT has not been oversold, but rather has a great impact on symptom reduction and enhancing concordance and insight. Perhaps the most informative trial so far accomplished has been the work on cognitive therapy for command hallucinations, which has proven the benefit of specific model development, and which productively, combined measurement of process and a targeted outcome.⁵⁹

There is ample evidence suggesting that a combination of family and psychological interventions, alongside pharmacotherapy, can be the most effective way of dealing with refractory AVH.⁶⁰ The inner dialogue hypothesis of AVH held by CBT therapists has its opponents.⁶¹ Patients respond to the voices they experience by utilising inner speech. Some observations with corresponding features weaken the inner-dialogue hypothesis. David and Lucas have demonstrated in a single case study that short-term maintenance of phonological representation (inner dialogue) may co-exist with AVHs – they are not synonymous experiences. The cost-effectiveness of psychological interventions is poorly studied, despite being highly relevant for policy decisions in healthcare.

Computerised voice therapy works better with technically minded, highly intelligent patients. In contrast, individuals of low to average intelligence may require a primarily behavioural approach, with limited efforts to understand concepts, such as automatic thinking and schema. Unlike sound therapy through music playing instruments (iPad, iPod, iPhone, etc.), TCI causes no disruption to daily functioning and can be used continuously. Computerised voice therapy and sound therapy warrant standardised case trials. When it comes to treating AVHs, optimizing compliance, reducing the burden of symptoms, and improving control, quality of life and social functioning should be the therapeutic goals.⁶² Neuroquantological views of AVHs⁶³ explain the limitations of pharmacotherapy and the usefulness of psychological interventions.

The Issues

Supporting Professional Activities (SPA) time is a part of each consultant’s new contract. When the new consultant contract evolved in 2003, a suggested breakdown of the week was 7.5 sessions (1 session equates to 4 hours) for direct clinical care (DCC) and 2.5 sessions for SPAs.¹ This was driven by the need for consultants to continue their own professional development (CPD) as well as having the time for input into the development of trainees and medical students.

Examples of CPD work for consultants could include audit for improvement of service or patient care, teaching of patients, medical students or trainees, research, publications, aspects of hospital management and involvement in simulation courses e.g. Advanced Life Support (ALS)/Advanced Paediatric Life Support (APLS).

The General Medical Council (GMC) requires that during annual appraisals, doctors should use supporting information to demonstrate they continue to follow “Good Medical Practice”. This mandates that doctors should ‘take part in educational activities that maintain and further develop’ their competence and performance.¹ With regard to revalidation, the GMC states you will have to demonstrate that you regularly participate in these activities; at Annual Review of Competency Progression (ARCP) it is imperative that accurate records of these CPD activities are presented at the annual job plan review.²

It is clear, therefore, that the provision of allocated time during the working week to complete these aspects of work life are deemed necessary for consultants. The Royal College of Anaesthetists and Association of Anaesthetists of Great Britain and Ireland both support the original view that a consultant should “typically” have 2.5 SPAs in their contract (though this would have to be subject to individual workload). With the demands of service provision it is clear that consultant SPAs are under threat, with around 40% of new consultants offered jobs with fewer SPA sessions than are thought necessary to allow sufficient non-DCC work.³

Since trainees are subject to similar appraisal and development requirements, we wonder if trainees should be allocated SPA time? For progression through training years and to pass the ARCP, it is necessary to provide evidence of trainee development within clinical practice in a similar way to consultants. This can involve a great deal of extra time. Once (notoriously difficult) exams have been passed, each trainee must go through the application process and prove what skills they have assimilated during their training to date. In fact, the ST3 anaesthesia application criteria states that the following are some of the ‘desirable’ criteria that require evidence:

• Relevant academic and research achievements
• Involvement in an audit project, or quality improvement project
• Interest and commitment to the specialty beyond the mandatory curriculum
• Evidence of interest in, and experience of, teaching
• Instructor status in an advanced life support course (ALS, APLS)
• Involvement in management…and understanding of management
• Effective multi-disciplinary team working and leadership
• Effective leadership in and outside medicine
• Achievement outside medicine
• Altruistic behaviour, e.g. voluntary work

The list is extensive and clearly requires a lot of time and input outside of the normal working week. With the expectation that trainees should be prepared to move straight from CT2 to ST3 (assuming their exams are completed), these desirable criteria must be addressed alongside completing other mandatory aspects of training such as, for anaesthesia: an Initial Assessment of Competency (IAC), an Intensive Care Unit (ICU) module, an Initial Assessment of Obstetric Competency (IAOC) and 15 Units of Training. With all these challenges between a core anaesthetic trainee and potential specialist anaesthetic training, there seems little time to complete an adequate number of the desirable criteria; this is a compelling reason to facilitate some time into the trainee contract to help produce more well rounded trainees.

However, therein lies the challenge - anaesthetic training is such a busy programme. Trainees are involved with multiple areas within a hospital such as ICU, theatre work or Obstetric Delivery Suite that they must learn and practice a wide range of skills to demonstrate the proficiency expected of a consultant anaesthetist. With experience of clinical work already at a premium due to European Working Time Directive hours, creating a good teaching environment whilst providing service provision is a hard enough task. It might seem difficult, therefore, to justify taking away yet more clinical time for trainees.

The proposed “7 day National Health Service (NHS)” contract could also pose more difficulties. Current example rotas released by NHS Employers demonstrate an increased likelihood of shift-work for a typical ICU rota.⁴ This shows trainees will be working more weekends and nights than at present, which could reduce the time spent directly with consultants. This would make introducing more non-DCC work difficult to justify as it would likely occur during daylight hours – when training could occur.

How it could be introduced:

Assuming SPA sessions for trainees were implemented, there would also be practical aspects to address. For example, how many SPA sessions to allocate for each level of trainee and how to monitor that this time was spent effectively and efficiently.

Monitoring:

Trainees could propose which aspects to focus on during their SPA sessions, such as management, teaching, quality improvement projects or more time in their sub-specialty interest. The goals could then be set at the initial educational supervisor meeting, much like a Personal Development Plan (PDP), and monitored throughout the year. This would give focus to any SPA time and ensure it is effectively used. If a trainee abuses their time or is not using it appropriately then removal of SPA time could be enforced. This would give the trainees more ability to improve the skills so often considered additional to trainees.

Funding:

In times of NHS austerity, funding would also need addressing. Potentially neither Deanery nor Trust might be willing to pay a doctor for days spent working outside the hospital workload – such as in educational roles or as a college tutor.⁵ A trial in one single deanery could assess the efficacy of such a scheme.

A possible solution would be to remove a few days of study leave allowance, as many trainees do not use their whole entitlement, and re-assign these to SPA time, allowing a trainee more flexibility. Trainees could initially start with fewer SPA sessions when more junior, to allow more clinical time, increasing SPAs to one per week for intermediate or higher trainees who may well be approaching their Certificate of Completion of Training (CCT).

Conclusion:

There are some practical difficulties in establishing trainee SPA sessions and no doubt many feel all contracted time should be spent practicing anaesthesia. However, given the changing way trainees are recruited via a ‘tick-box’ national application system, together with the variety of non-clinical skills expected by consultancy such as an ability to teach, conduct audit work, engage in managerial roles etc., a small change in the training set-up could produce more rounded trainees, benefitting anaesthesia in general and training programmes in the future.

INTRODUCTION

Ventilator-associated pneumonia (VAP) is a type of nosocomial pneumonia that occurs in patients who receive mechanical ventilation and is usually acquired in the hospital setting approximately 48–72 hours after mechanical ventilation.¹ VAP is one of the most frequent hospital-acquired infections occurring in mechanically ventilated patients and is associated with increased mortality, morbidity, and health-related costs. Several risk factors have been reported to be associated with VAP, including the duration of mechanical ventilation, and the presence of chronic pulmonary disease, sepsis, acute respiratory distress syndrome (ARDS), neurological disease, trauma, prior use of antibiotics, and red cell transfusions.² VAP occurrence is closely related to intubation and the presence of the endotracheal tube (ETT) itself.

Since there are inadequate objective tools that are utilized to make an assessment of bacterial-induced lung injury in a heterogeneous group of hosts, the diagnosis of VAP is challenging. Around 90% of ICU-acquired pneumonias occur during mechanical ventilation, and 50 % of these ventilator-associated pneumonias begin in the first 4 days after intubation.³ VAP has a cumulative incidence of 10-25% and accounts for approximately 25% of all ICU infections and 50% of its antibiotic prescription, making it the primary focus for risk-reduction strategies.^1,4 For all these reasons, early diagnosis and prevention of VAP has held a prominent position on the research agenda of intensive care medicine in the past 25 years, with an ultimate goal of improving patient outcome, preferably by reducing mortality.

The keywords, ‘ventilator-associated pneumonia,’ in PUBMED revealed a total of 3612 titles and 625 review articles within the search limit of 10 years, between 2005 and 2014. Only articles in English were chosen.

PATHOGENESIS

Understanding the pathogenesis of VAP is the first step in the formulation of its appropriate preventive and therapeutic strategies. The initial step in the pathogenesis of VAP is bacterial colonization of the oropharynx and gastric mucosa, followed by translocation of the pathogens to lower respiratory tract. The most common means of acquiring pneumonia is via aspiration which is promoted by supine position and upper airway and nasogastric tube placement.^2,5 In a mechanically ventilated patients, aspiration occurs around the outside of the endotracheal tube rather than through the lumen. Secondly, aerobic Gram-negative bacteria presumably reach the lower airway via aspiration of gastric contents or of upper airway secretions. Other means by which VAP can be acquired include aspiration from the stomach or nose and paranasal sinuses. Figure 1 depicts the essential elements favoring colonization of lower respiratory tract with the bacterial pathogens with subsequent development of pneumonia.^2,5,6

Figure 1: Pathogenesis of Ventilator-associated pneumonia⁵
*Gastric alkalinization; prior antimicrobials; ICU stay; intubation; supine position; circuit/airway manipulation and mishandling; device cross-contamination; sedation; diminished cough reflex; and malnutrition predispose to colonization and aspiration. As the duration of ICU stay increases, colonization with MDR Gram-negative pathogens like Pseudomonas and Acinetobacter increases.
†Via contaminated nebulizers/aerosols
Reproduced with permission from the publisher.

COMMON CAUSES

The specific microbial causes of VAP vary widely depending in epidemiological and clinical factors. Common pathogens include aerobic gram negative bacteria such as Pseudomonas aeruginosa and members of family Enterobacteriaceae, staphylococci, streptococci, and Haemophilus species. Microorganisms like Pseudomonas spp., Acinetobacter spp. and Methicillin-Resistant Staphylococcus aureus occur commonly after prior antibiotic treatment, prolonged hospitalization, mechanical ventilation or when other risk factors are present.^6,7

Moreover, deliberated ill patients may have defect in phagocytosis and behave as functionally immunosuppressed even prior to emergence of nosocomial infection as seen by many recent studies.^8,9

DIAGNOSIS

Clinical Diagnosis

No gold standard of diagnosis for identifying VAP is there inspite of variety of proposed definitions. VAP has traditionally been diagnosed by clinical criteria of Johanson and colleagues (appearance of new or progressive pulmonary infiltrates, fever, leucocytosis and purulent tracheobronchial secretions), which are non-specific. When findings on histologic analysis and cultures of lung samples obtained immediately after death were used as references, a new and persistent (>48-h) infiltrate on chest radiograph plus two or more of the three criteria (i) fever of >38.3°C, (ii) leukocytosis of >12 × 10⁹/ml, and/or (iii) purulent tracheobronchial secretions had a sensitivity of 69% and a specificity of 75% for establishing the diagnosis of VAP.¹⁰

Because of the poor specificity of the clinical diagnosis of VAP and of qualitative evaluation of ETAs, Pugin et al. developed a composite clinical score, called the clinical pulmonary infection score (CPIS), based on six variables: temperature, blood leukocyte count, volume and purulence of tracheal secretions, oxygenation, pulmonary radiography, and semi-quantitative culture of tracheal aspirate. The score varied from 0 to 12. A CPIS of >6 had a sensitivity of 93% and a specificity of 100%.¹¹ Accuracy of CPIS in diagnosis of VAP is debated, despite of its clinical popularity. In one meta-analysis study evaluating the accuracy of CPIS in diagnosing VAP reported pooled estimates for sensitivity and specificity for CPIS as 65 % (95 % CI 61-69 %) and 64 % (95 % CI 60-67 %), respectively.¹² The poor accuracy of clinical criteria for diagnosing VAP is due to purulent tracheobronchial secretions in patients receiving prolonged mechanical ventilation which are rarely caused by pneumonia. Moreover, in pneumonia systemic signs such as fever, tachycardia, and leukocytosis are nonspecific; they can be caused by any state that releases the cytokines interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor alpha (TNFα), and gamma interferon.^13,14 The weak point of CPIS is probably the inter-individual variability (kappa= 0.16), since a subjective evaluation is required when we are judging the quality of tracheal secretion (purulent/not purulent) and the presence of infiltrate at chest ray.¹⁵

Radiologic Diagnosis

Radiographical evidence of pneumonia in ventilated patients is also notoriously inaccurate. In a study of autopsy proven VAP, of the total population, only air bronchograms correlated with pneumonia and no specific roentgenographic sign correlated with pneumonia in patients with adult respiratory distress syndrome. The differential diagnoses of VAP based on radiographical appearance, include adult respiratory distress syndrome, congestive heart failure, atelectasis, pulmonary embolism and neoplastic infiltration.¹⁶

Microbiologic Diagnosis

The type of specimen that should be obtained for microbiologic processing as soon as VAP is suspected is another area of importance. The use of quantitative cultures is one of the main issues for any diagnostic laboratory because there is oropharyngeal bacterial contamination of all respiratory secretion samples, despite this is not always undertaken in many hospitals today.^16,17

Blood cultures

Blood cultures have limited value because organisms isolated from blood in suspected VAP cases are often from extrapulmonary sites of origin.¹⁸ Blood cultures in patients with VAP are clearly useful if there is suspicion of another probable infectious condition, but the isolation of a microorganism in the blood does not confirm that microorganism as the pathogen causing VAP.

Quantitative cultures of airway specimens

Simple qualitative culture of endotracheal aspirates has high percentage of false-positive results due to bacterial colonization of the proximal airways observed in most patients in the ICU.²⁰ Quantitative culture techniques suggest that endotracheal aspirate cultures (QEA) may have an acceptable overall diagnostic accuracy, similar to that with several other, more invasive techniques including BAL, protected BAL (pBAL) ,protected specimen brush (PSB) or tracheobronchial aspirate(TBA).^7,19,20 Threshold values often employed for diagnosing pneumonia by quantitative cultures are ≥10⁵ to 10⁶, ≥10⁴, and ≥10³ CFU/ml for QEA, bronchoscopic BAL, and PSB, respectively, with ≥10⁵ CFU/ml being the most widely accepted value for QEA.^21,22,23 Also, blind aspiration sampling can lead to errors but bronchoscope also carries risks, such as inducing cardiac arrhythmia, hypoxemia, bleeding, pneumothorax, along with greater costs both in terms of time and resources. It is accepted that before administering the first dose of antibiotic or before any change in treatment patient specimens for culture should be taken, so that the results interpreted are valid.²⁴ Lalwani et al., in their study, observed that culture results of a properly collected tracheal aspirate should be taken into consideration along with Centre for Disease Control and Prevention (CDC's) diagnostic criteria to maximize the diagnosis of VAP.²⁵

The recent guidelines of Society for Healthcare Epidemiology of America/ Infectious Diseases Society of America (SHEA/IDSA) recommend Gram staining of endotracheal aspirates. However, the sensitivity (57-95%) and specificity (48-87%) of this technique are highly variable. The role of procalcitonin and other biomarkers for the diagnosis of VAP is yet unsubstantiated.^5,26

Since VAP diagnosis founded on radiographic findings of pneumonia, which have intrinsic variability in technique, interpretation, and reporting, and on clinical signs and symptoms- that are subjective- in 2011 a Working Group of the CDC proposed a new approach to surveillance for Ventilator-Associated Events (VAE). Table 1 According to the new CDC definition algorithm, VAP is an Infection-related Ventilator-Associated Complication (IVAC) occurring after 3 days of mechanical ventilation and 2 days before or after the onset of worsening oxygenation, if purulent respiratory secretions with positive cultures or objective signs of respiratory infection have been found.²⁷

Table 1: CDC Algorithm for VAP diagnosis³⁰

Table 2: Practices for which insufficient evidence or no consensus exists about Efficacy^8,57

STRATEGIES FOR VAP PREVENTION

There are multiple recommended measures for prevention of VAP. Practices for which insufficient evidence or no consensus exists about efficacy are summarized in Table 2. Preventive VAP strategies can be grouped into two classes: non-pharmacologic strategies, which are focused on preventing aspiration, and pharmacologic strategies, which are aimed at preventing colonization.

Non-Pharmacologic Strategies

Staff Education in the Intensive Care Unit

Various barriers to adhering to VAP prevention recommendations include disagreement with the reported results of source studies, resource paucity, elevated costs, inconvenience for nurses, fear of potential adverse effects and patient discomfort. There is considerable variability in practice between countries regarding humidification systems, intubation route, endotracheal suction system, kinetic therapy beds, subglottic secretion drainage and body position. For efficient patient care staffing must be sufficient while ensuring that staff is able to comply with essential infection control practices and other prevention strategies.^17,28

Hand Hygiene

Microorganisms can be spread easily from patient to patient on the hands of healthcare workers. Moreover, wrist watches, rings, bangles and other jewelry commonly act as reservoirs for organisms, and impede effective hand cleaning. Moreover, healthcare workers compliance to hand hygiene is low, and high workload decreases their compliance.²⁹

Impact of patient position

Patients positioned semi-recumbently 45 degrees have significantly lower incidence of clinically diagnosed VAP compared to patients positioned supinely.³⁰ Moreover, the incidence of clinically diagnosed VAP among patients positioned prone, does not differ significantly from the incidence of clinically diagnosed VAP among patients positioned supine.^31,32

Kinetic Beds

Critical patients often for a long time remain immobile in the supine position so the functional residual capacity is decreased because of alveolar closure in dependent lung zones and impaired mucociliary clearance. This leads to the accumulation of mucus, atelectasis onset and ensuing infection.³³ Rotational therapy uses a special bed designed to turn continuously, or nearly continuously, the patient from side to side; specific designs include kinetic therapy and continuous lateral rotation therapy (CLRT).^34,35

Artificial Airway Management

Oral vs Nasal Intubation: Both nasogastric and nasotracheal tubes can cause oropharyngeal colonization and nosocomial sinusitis. Thus, use of the oral route for both endotracheal and gastric intubation should be considered to decrease the risk of VAP.³⁶

Endotracheal tube cuff pressure: The secretions that pool above inflated endotracheal tube cuffs may be a source of aspirated material and ensuing VAP. The pressure of the endotracheal tube cuff should be optimized in order to prevent the leakage of colonized subglottic secretions into the lower airways. Persistent pressures into the tube cuff below 20 cm H₂O have been associated with the development of VAP.³⁷

Silver-Coated Endotracheal Tubes: Silver-coated endotracheal tubes appear to be safe, reduces bacterial biofilm formation, has bactericidal activity, reduces bacterial burden and can delay airway colonization. However, further studies are needed to for determing its efficacy.^38,39

Mechanical Ventilation Management

Ventilator Circuit Change: The CDCs recommendation was ‘do not change routinely, on basis of duration of use, the breathing circuit that is in use on an individual patient. Change the circuit when it is visibly soiled or mechanically malfunctioning.⁴⁰

Humidification With Heat and Moisture Exchangers: The effect of HME in preventing VAP is still controversial and recent studies have failed to show a significant difference in rates of infection.⁴¹

Subglottic secretion drainage: Intermittent subglottic secretions drainage using inspiratory pause during mechanical ventilation results in a significant reduction in VAP.⁴² SSD reduces VAP in patients ventilated for >72 hours and should be considered with other recommended strategies such as semi-recumbent positioning.⁴³

Pharmacologic Strategies

Modulation of Oropharyngeal Colonization

Policies encouraging routine tropical oral decontamination with chlorhexidine for patients merit reevaluation. It is a cheap measure, but whether is it a safe one − it does not select resistant microorganisms − remains to be investigated.^8,44

Selective Decontamination of the Digestive Tract

Selective decontamination of the digestive tract (SDD) is the decontamination ofpotentially pathogenic microorganisms living in the mouth and stomach, whilst preserving the indigenous anaerobic flora. SDD is an effective and safe preventive measure in ICUs where incidence rates of MRSA and VRE are low, but in ICUs with high rates of multi-resistant microorganisms it is a measure that is effective but not safe.^45,46

Stress Ulcer Prophylaxis

Patients at risk from important gastrointestinal bleeding (shock, respiratory failure requiring mechanical ventilation or coagulopathy) should receive H₂ antagonists such as ranitidine rather than sucralfate.⁴⁷

Ventilator sedation protocol

In patients receiving mechanical ventilation and requiring sedative infusions with midazolam or propofol, the use of a nurse-implemented sedation protocol decreases the rate of VAP and the duration of mechanical ventilation.⁴⁸ An objective assessment-based Analgesia-Delirium-Sedation (ADS) protocol without daily interruption of medication infusion decreases ventilator days and hospital length of stay in critically ill trauma patients.⁴⁹

Antibiotic Policy and Infection Control

Rational antibiotic policy is a key issue for better patient care and preventing antimicrobial resistance.^50,51 Infection control programs like using a scheduled switch of antibiotic class have demonstrated efficacy in reducing nosocomial infection rates and restraining multidrug resistant (MDR) microorganism emergence.⁵²

VAP prevention in low resource/developing countries

Though the incidence of VAP has declined in the developed countries, it continues to be unacceptably high in the developing world. Its incidence in these countries is 20 times that in the developed nations with significant morbidity, mortality, and increase in ICU length of stay, which may represent an additional burden on the scarce resources in developing countries.⁵³ Insufficient preventive strategies and probably inappropriate antibiotics administration may have lead to this scenario. Since microbiology and resistance pattern in India is different from other countries, there is need for data from our country to choose appropriate antimicrobials for management.⁵⁴ Simple and effective preventive measures can be instituted easily and at minimal costs. Such measures might include hand hygiene, diligent respiratory care, elevation of head, oral and not nasal cannulation, minimization of sedation, institution of weaning protocols, judicious antibiotics use, de-escalation, and leveraging PK/PD characteristics for antibiotics administered. More costly interventions should be reserved for appropriate situations. Strategies to prevent VAP, probably by emphasis on practical, low-cost, low technology, easily implemented measures is need of the hour.

Ventilator-associated events (VAE) surveillance: an objective patient safety opportunity

Surveillance for ventilator-associated pneumonia is challenging and contains many subjective elements, including the use of chest x-ray evidence of pneumonia. In January 2013, CDC convened a VAP Surveillance Definition Working Group which transitioned VAP surveillance to ventilator-associated event (VAE) surveillance in adult inpatient settings.⁵⁵ The VAE algorithm—which is a surveillance algorithm and not intended for use in the clinical management of patients—consists of 3 tiers of definitions: Tier 1, Ventilator-Associated Conditions (VAC); Tier 2, Infection -related Ventilator-Associated Complications (IVAC); and Tier 3, Possible and Probable VAP.²⁷ The tier 1, VAC attempts to identify sustained respiratory deterioration episodes, and capture both infectious and noninfectious conditions and complications occurring in patients receiving mechanical ventilation. The tier 2, IVAC, is intended to identify the subset of VACs that are potentially related to pulmonary and extra pulmonary infections of sufficient severity to trigger respiratory deterioration. The tier 3, possible and probable VAP, attempts to identify IVAC patient subsets with respiratory infections as manifested by objective evidence of purulent respiratory secretions (where purulence is defined by using quantitative or semi-quantitative criteria for the number of neutrophils on Gram stain) and/or positive results of microbiological tests done on respiratory specimens. Because of the wide range of the lower respiratory tract specimens, their collection procedure as well as in laboratory processing and reporting of results, the Working Group of CDC determined that it was not appropriate to include these data elements in the VAC and IVAC definitions.⁵⁶

This 3 tier approach is ineffective to accurately identify VAP for surveillance purposes and focuses on more mechanical ventilation complications. This approach may also reduce the likelihood of manipulation that could artificially lower event rates. Most VAEs are caused by pneumonia, pulmonary edema, atelectasis, or acute respiratory distress syndrome. In few recent studies concordance between the VAE algorithm and VAP was found to be poor.⁵⁷ Thus, more studies are needed to further validate VAE surveillance compared with conventional VAP by using strong microbiologic criteria, particularly bronchoalveolar lavage with a protected specimen brush for diagnosing VAP and to better characterize the clinical entities underlying VAE.

Bundle approach to prevention of VAP

One of the five goals of the ‘Saving 100,000 Lives’ campaign, launched by the Institute for Healthcare Improvement is to prevent VAP and deaths associated with it by implementing a set of interventions for better patient care known as the ‘ventilator bundle’. The interventions should have scientific support of effectiveness, based on randomized controlled trials. All the elements of the bundles must be executed at the same time. The bundles for VAP includes four components: (a) elevation of the head end of the bed to 30-45º, (b) daily interruption of sedation, (c) daily assessment of readiness to extubate and (d) prophylaxis for deep venous thrombosis and peptic ulcer disease. The bundle approach to prevention of VAP has been found to be highly effective in reducing the incidence, mortality and ICU stay.^5,58,59 The ventilator bundle should be modified and expanded to include specific processes of care that have been definitively demonstrated to be effective in VAP reduction. A multidimensional framework with a long-lasting program can successfully increase compliance with preventive measures directly dependent on healthcare workers bedside performance.

CONCLUSION

Ventilator Associated Pneumonia is one of the most common nosocomial infections in ICU presenting with non specific symptoms and clinical signs. Quantitative culture obtained by different methods, including EA, BAL, pBAL, PSB or TBA seem to be rather equivalent in diagnosing VAP. Clinical criteria used in combination, may be useful in VAP diagnosis; however, inter-observer variability and the moderate performance are to be considered.

Preventive strategies should focus on better secretion management and on reduction in bacterial colonization. Further research on targeted interventions is needed to effectively reduce VAP incidence. For VAP an approach based on multidisciplinary group is required including setting preventive benchmarks, establishing goals and time lines and providing appropriate education and training, audits and feedback to the staff, while continually updating themselves based on relevant clinical and preventive strategies.

INTRODUCTION

During my placement in Psychiatry at the Brooker Centre, Runcorn, UK, I have come into contact with a wide array of psychiatric disorders, none more so than borderline personality disorder (BPD). It is undoubtedly one of the most prevalent problems in the area which the Brooker Centre serves. I can recall an example of a patient with BPD who had been quite unwell for a prolonged period of time and had struggled with affective instability. This patient had been quite successfully treated with Lithium therapy, has exhibited stability and is happy on the current treatment. There is a pattern of pharmacological treatment in BPD patients despite the fact that guidelines suggest otherwise…

Personality disorders are defined as ‘an enduring pattern of inner experience and behaviour that deviates markedly from the expectations of the individual’s culture, is pervasive and inflexible, has an onset in adulthood, is stable over time, and leads to distress or impairment’ . Personality disorders are representative of long-term functioning and are not considered in terms of episodes of illness ¹.

The Diagnostic and Statistical Manual of Mental Disorders, 5^th edition (DSM-5), groups the various personality disorders into three clusters based on their descriptive similarities.

Cluster A includes the Paranoid, Schizoid, and Schizotypal personality disorders which are categorised as ‘odd/eccentric’;

Cluster B includes the Antisocial, Borderline, Histrionic, and Narcissistic personality disorders which are categorised as ‘dramatic/emotional/erratic’;

Cluster Cincludes the Avoidant, Dependent, and Obsessive-compulsive personality disorders which are categorised as ‘anxious/fearful’ ².

The International Classification of Diseases, 10^th edition (ICD-10), specifies the condition of emotionally unstable personality disorder which has two subtypes: The impulsive type and the borderline type. The borderline type in essence overlaps with the DSM-5 definition ³.

It has proven difficult to provide robust clinical recommendations with regards to the treatment of personality disorder. This is, in part, due to the fact that study populations are diverse but also compounded by the use of different assessment criteria. Furthermore, it is important to consider that personality disorders often present with a great deal of psychiatric comorbidity. Of the personality disorders, particular attention has been paid to borderline personality disorder (BPD) as the symptom clusters which it involves have been shown to improve considerably with treatment ⁴.

Figure 1: Diagnostic Criteria for Borderline Personality Disorder according to DSM-5 ²:

Borderline personality disorder is characterised by a pervasive instability in mood, interpersonal relationships, self-image and behaviour. The condition was first recognised in the United States by Adolf Stern in 1938. He described that these are a group of patients who neither fit into psychotic or psychoneurotic group, which gave rise to the term ‘borderline’. BPD is often diagnostically comorbid with depression and anxiety, eating disorders (notably bulimia), post-traumatic stress disorder, substance misuse and bipolar affective disorder. Furthermore, psychotic disorders have also been found to overlap. Due to this extent of comorbidity it is rare to see a patient who has a pure BPD ⁵.

The pharmacological treatments of BPD are tailored according to the symptom clusters that present. These include impulsivity, affective instability, transient stress-related psychotic symptoms and suicidal & self-injurious behaviours ^5,6.

Recommended Psychological and Pharmacological treatment, 2009 National Institute for Health and Clinical Excellence (NICE) guidelines on Borderline Personality Disorder ^{5, 7}:

Psychological

NICE guidelines state that when offering psychology for BPD or for the individual symptoms of the disorder, brief psychological interventions (i.e. less than a 3 month period) should not be used. It states that the frequency of psychotherapy sessions should be adapted to the patient’s needs and ‘context of living’ and suggests that twice-weekly session may be considered. The guidelines also specify that for women with BPD for whom recurrent self-harm is a priority, a comprehensive dialectical behaviour therapy programme should be considered. NICE recommends that when psychological treatment is provided in BPD, the effects should be monitored using a broad range of outcomes. These should include personal functioning, drug and alcohol use, self-harm, depression and the symptoms of BPD.

Pharmacological

The NICE guidance states that drug treatment should not be used specifically for BPD or for the individual symptoms or behaviour associated with the disorder (e.g. repeated self-harm, marked emotional instability, risk taking behaviour and transient psychotic symptoms). It goes on to suggest that antipsychotics should not be used for the medium- and long term treatment of BPD. However, with regards to the management of comorbidities, it specifies that drug treatment may be considered and that in each case, the NICE guidelines for each comorbid condition must be referred to. Antidepressants, mood stabilisers and antipsychotics are commonly used in clinical practice. The guidelines mention that short-term use of sedative medication may be considered in a crisis. ‘Short-term’ denotes treatment lasting no longer than one week.

With regards to drug treatment during a period of crisis, NICE recommends that there should be a consensus among prescribers and other involved professionals about the proposed drug treatment and also that a primary prescriber should be identified. There should be an appreciation of the likely risks of prescribing, including alcohol and illicit drug use. NICE emphasises that the psychological role of prescribing (both from the patient’s and prescriber’s perspective) should be taken into account, and the impact that such prescribing decisions may have on the therapeutic relationship and overall care plan. NICE recommends that a single drug be used and that polypharmacy is to be avoided as much as possible.

In a crisis NICE recommends prescribing ‘a drug that has a low side-effect profile, low addictive properties, minimum potential for misuse and relative safety in overdose.’ The minimum effective dose is favourable, prescribing fewer tablets more frequently if there is a significant risk of overdose and also agreeing with patient on the symptoms that are being targeted. NICE suggests that following a crisis, a plan should be made to stop drug treatment that was started during a crisis. If this is not possible, a regular review of the effectiveness, side effects, misuse and dependency of the drug is advised. BPD patients can often have concomitant insomnia and for this, NICE details basic advice regarding sleep hygiene and forwards on to the guidance on the use of zaleplon, zolpidem and zopiclone for the short-term pharmacological management of insomnia.

AIMS AND OBJECTIVES

This report will review the current guidelines specifically regarding the management of borderline personality disorder and explore the literature according to the research recommendations that are set by NICE. The report is to focus on the two aspects of the management of BPD – The psychological/psychosocial aspect and the pharmacological aspect.

CURRENT NICE GUIDELINES ON PSYCHOLOGICAL AND PHARMACOLOGICAL TREATMENT OF BPD ⁷:

Psychology

Mentalisation-based therapy and dialectical behavioural therapy are proposed in the setting of a ‘well structured, high quality community based service’ e.g. a day hospital setting or a community mental health team. NICE suggests that these techniques should be compared with ‘high-quality community care delivered by general mental health service without the psychological intervention for people with BPD’ in order to measure efficacy. For outpatients, cognitive analytic therapy, cognitive behavioural therapy, schema-focussed therapy and transference focussed therapy are suggested and are catered to those with less severe BPD (i.e. fewer comorbidities, higher level of social functioning, greater ability to depend on self-management methods). Randomised controlled trials reporting medium term outcomes (e.g. quality of life, psychosocial functioning, employment outcomes and BPD symptomatology) of a minimum of 18 months are recommended

Pharmacology

Mood stabilisers are proposed as it is detailed that emotional instability is a key feature in BPD. In particular, topiramate and lamotrigine are mentioned as they have been shown to produce encouraging results in small-scale studies. A randomised placebo-controlled trial with medium to long-term follow up is recommended.

ANALYSIS

Psychology: Dialectical Behaviour Therapy (DBT)

Dialectics can be defined as the art of investigating the relative truth of opinions, principles, and guidelines ⁸. Dialectical in DBT refers to a means of arriving at the truth by examination of the argument i.e. the ‘thesis’ and ‘antithesis’ and resolving the two into a rational synthesis. DBT was introduced in 1991 by Marsha Linehan (a psychology researcher) and colleagues tailored as a treatment for BPD. In this, patients are supported in understanding their own emotional experiences and are taught new skills for dealing with their stresses. A combination of individual and group sessions are used. More adaptive responses and effective problem-solving techniques are integrated to improve functioning and quality of life as well as improving morbidity and mortality ^{9, 10}.

A study published in 2015 by M. Linehan et al detailed a randomized clinical trial that set out to compare

1) Standard DBT (DBT group skills training + DBT individual therapy) with

2) A treatment that evaluated DBT group skills training with manual case management (i.e. with the removal of DBT individual therapy) and

3) A treatment that removed DBT skills training by providing only DBT individual therapy with an activities group and prohibited individual therapists from teaching DBT skills.

All 3 versions of the treatment were found to be comparably effective at reducing suicide attempts, suicidal ideation, medical severity of intentional self-harm, use of crisis services owing to suicidality and improving reasons for living ¹¹.

Psychology: Mentalization based therapy

Mentalization is ‘the process by which we make sense of each other and ourselves, implicitly and explicitly, in terms of subjective states and mental processes.’ It is a social construct suggesting that we are attentive to the mental states of those we are with, physically or psychologically ¹². Mentalization based treatment is a psychosocial treatment for BPD in which therapists monitor attachment and mentalizing capacity, and use interventions that aim to reinstate or maintain the capacity of patients to mentalize ¹³.

A longitudinal study, published in 2008, involving an eight-year follow-up of patients treated for BPD evaluated the effect of mentalization-based treatment (MBT) with partial hospitalization compared with treatment as usual. Five years after discharge from MBT, the MBT group exhibited clinical and statistical superiority to treatment as usual measured on suicidality, diagnostic status, service use, medication use, global function and vocational status ¹⁴. A more recent review article, published in 2015, emphasises the consideration of disruptions in three closely related domains in individuals with BPD. These are ‘in attachment relationships, in different polarities of mentalizing, and in the quality of epistemic vigilance and trust’. It is suggested that this approach allows seemingly paradoxical features of BPD patients appear more coherent. It is supposed that this approach provides a clear focus for the therapist enabling them to monitor the therapeutic process in terms of imminent mentalizing impairments and epistemic mistrust due to activation of the attachment system.

The article goes on to assert that the effectiveness of MBT in BPD may be elucidated due to the fact that it ‘enables the therapist to maintain and foster a mentalizing stance, even–and perhaps particularly–under high arousal conditions that are so characteristic of work with these patients’ ¹⁵.

Psychology: Cognitive analytic therapy (CAT)

CAT is a brief focal therapy that is informed by cognitive therapy, psychodynamic psychotherapy and elements of cognitive psychology. It was originally developed by Anthony Ryle tailored towards the needs of the NHS ¹⁶. It is based on a collaborative therapeutic position which sets out to create narrative and diagrammatic reformulations with patients concerning their difficulties. The theory centres on descriptions of sequences of linked external, mental and behavioural events. At first, the emphasis was on how such procedural sequences prevented revision of dysfunctional ways of living. More recently, this has been extended to understanding the origins of reciprocal role procedures in early life and their repetition in current relationships and self-management ¹⁷.

One study detailed a randomised controlled trial which aimed to investigate the effectiveness of time-limited CAT for participants with personality disorder. The study found that participants receiving CAT exhibited reduced symptoms and showed considerable improvement compared with the control group who showed signs of deterioration during the treatment period. They concluded that CAT is superior to treatment as usual in improving outcomes associated with personality disorder ¹⁸.

Psychology: Cognitive behavioural therapy (CBT) and Schema-focussed therapy

CBT is a time-limited, problem focussed psychotherapy that has been applied to a wide range of psychiatric disorders. The development of this technique was born out of the observation that patients referred for psychotherapy often would hold ingrained, negatively skewed assumptions of themselves, their future and their environment. The therapy is based on the notion that disorder is caused not by life events, but by the view the patient adopts of events. The therapy focusses on current problems and helps to develop new skills to provide symptom relief and sustain recovery ^{9, 19}.

Initially CBT was predominantly insight-orientated, using introspection to bring about change. Beck et al began to integrate a range of behavioural techniques to improve the impact on dysfunctional controlling belief systems (schemas). The goal of treatment is not to replace the dysfunctional schemas; it aims to modify beliefs and develop new ones allowing the patient to cope more effectively in challenging situations ^{20, 21}.

A 2013 review article that set to explore schema-focussed therapy concluded that schema-therapy is based on a ‘cohesive theoretical model’ and that there seems to be sufficient evidence supporting its validity. Regarding effectiveness, it goes on to indicate that one should be encouraged by the results of studies, however it points out that due to the small number of ‘methodologically-good efficacy studies’ it is difficult to be certain. The article claims that when evaluated against other psychotherapeutic treatments, specifically DBT and MBT, schema-therapy requires more investigation ²². A pilot study (2013) set out to monitor the effects of group schema-based CBT on global symptomatic distress in young adults with personality disorders or features of personality disorder. Their findings provide preliminary evidence that schema-based CBT might be an effective treatment ²³.

Furthermore, there is a multicentre randomized controlled trial being conducted with the aim of investigating schema-focussed therapy versus treatment as usual in BPD, which has a closing date of 1^st February 2016 ²⁴.

Psychology: Transference focussed therapy (TFT)

The classic use of the term transference originates in psychoanalysis and comprises “the redirection of feelings and desires and especially of those unconsciously retained from childhood toward a new object” ²⁵. Transference-focussed psychotherapy is an evidence-based manualised treatment using a psychodynamic approach with a focus on object relations theory ²⁶. TFT aims to ‘facilitate the reactivation, under controlled circumstances, of the dissociated internalised object relations in the transference relationship to observe the nature of the patient’s split polarised internal representations, and then, through a multistep interpretive process, work to integrate them into a fuller, richer, and more nuanced identity ²⁷.

Yeomans et al produced an article in 2013 consisting of vignettes to illustrate the techniques used in TFT with the view to evaluate its use in treating BPD. Their findings supported the validity of TFT in treating BPD patients who specifically had difficulty with relationships.

They distilled TFT down to three important components ²⁸:

1) The treatment contracting/setting the frame

2) Managing one’s affective response

3) The interpretative process

Pharmacology

A Cochrane intervention review assessing the effects of drug treatments in BPD, included twenty-eight randomised control trials, published in the period 1979-2009 (20 of 28 trials dating from 2000 or later), involving a total of 1742 participants ²⁹.

Figure 2: The pharmacological agents that were tested included the following:

The authors arrived at the conclusion that pharmacotherapy in BPD ‘is not based on good evidence from trials’. The review found that there is support for the use of Second-generation antipsychotics (in improving cognitive-perceptual symptoms and affective dysregulation); Mood stabilisers (in diminishing affective-dysregulation and impulsive-aggressive symptoms); and Omega-3 fatty acids.

However, these claims were made based on single study effects and therefore require replication. No drug was found to significantly affect the symptom clusters, specific to BPD, including avoidance of abandonment, chronic feelings of emptiness, identity disturbance, and dissociation.

One noteworthy finding was that Olanzapine was associated with an increase in self-harming behaviour. Furthermore, the review states that ‘special attention’ is needed in BPD when prescribing tricyclic antidepressants (due to toxic effects in overdose) and hypnotics & sedatives (due to there being potential for misuse or dependence). Another problem that was highlighted was that in comorbid eating disorders the use of Olanzapine can contribute to weight gain and Topiramate can produce weight loss.

The review goes on to elucidate that there is not any evidence from randomised controlled trials that any drug reduces the severity of BPD and that it consists of ‘distinct pathology facets’. They recommend that the pharmacotherapy of BPD should be targeted at ‘defined symptoms’ and that polypharmacy is not supported by the latest evidence and should be avoided as much as possible.

The authors end by reaffirming that the evidence is not robust and that the studies may not satisfactorily reflect certain characteristics of the clinical environment. They propose that further research is needed in order to produce reliable recommendations. They detail the complications that arise from the ‘polythetic nature’ of BPD i.e. each patient is likely to experience different aspects of the disorder. There lacks a consensus among researchers about a common battery of outcome variables and measures. They comment that there is a fragmentary view on drug effects and that it is unknown as to how the alteration of one symptom affects another.

Comorbidity

Comorbidity is a foremost concern in the interpretation of data concerning personality disorders ³⁰. A majority of individuals diagnosed with one personality disorder often meet criteria for at least one other personality disorder ³⁰. A large proportion of patients with personality disorder have one axis I ³¹ disorder comorbidly, mostly depression, anxiety and alcohol and substance use disorders ³². [Axis I is a reference to the multi-axial classification system used in the Diagnostic and Statistical Manual of Mental Disorders that was removed in the latest version, DSM-5 ²

It is important to consider therefore that, an improvement in the symptom clusters in personality disorders might be an improvement in comorbid axis I disorder symptoms. It is reported that the rates of depression are very high in BPD ³³ and that the response to antidepressants in depressed individuals with comorbid personality disorders appears lower than in those without comorbid personality disorder ³².

The most recent guidance on the treatment of BPD from the National Health and Medical Research Council of Australia (NHMRC), which reviewed the literature and integrated a series of meta-analyses, details that pharmacotherapy does appear to be effective in altering the nature and course of BPD and that evidence does not warrant the use of pharmacotherapy as a sole or first-line treatment for BPD ³⁴.

DISCUSSION

All of the aforementioned psychotherapy techniques are shown to produce promising results when applied to the treatment of BPD, with some standing out, such as DBT and MBT, due to the presence of a relatively robust evidence base. With such a wide variety of different approaches that all show some propensity for successful treatment of BPD it is clear that these approaches must be taken more seriously in clinical practice. These treatments have been shown to considerably improve symptomatic outcomes however there is a shortcoming in that they have failed to significantly improve social functioning. Each of the therapies follow distinct theories, however, when each treatment modality is applied to BPD, similar effects are seen. This is intriguing and should be explored further.

An analysis of these therapies revealed some common features which are now suggested as core requirements for all effective psychotherapeutic treatments:

Figure 3: Five common characteristics of evidence-based treatments for BPD ^{35, 36}.

An update to the aforementioned Cochrane review ²⁹ was published in 2013. The update focussed on the psychotherapies that are available for the treatment of BPD and included a total of 1804 participants spread over 28 studies. The psychotherapies discussed were divided into ‘comprehensive’ if they substantially involved an individual psychotherapy element or as ‘non-comprehensive’ if they did not. The comprehensive therapies included dialectical behaviour therapy, mentalization-based therapy (delivered in either a partial hospitalisation or outpatient setting), transference-focussed therapy, cognitive behavioural therapy, dynamic deconstructive psychotherapy, interpersonal psychotherapy and interpersonal therapy for BPD. These were assessed against a control condition and also with some direct comparisons against each other. Non-comprehensive psychotherapies included DBT-group skills training, emotion regulation group therapy, schema-focussed group therapy, systems training for emotional predictability and problem solving for borderline personality disorder (STEPPS), STEPPS plus individual therapy, manual assisted cognitive treatment, and psychoeducation ³⁷.

The authors concluded that both comprehensive and non-comprehensive therapies indicated beneficial effects for the core pathology of BPD and associated general psychopathology. The authors identified that dialectical behaviour therapy had been studied the most comprehensively followed by mentalization-based therapy, transference-focussed therapy, schema-focussed therapy and STEPPS. However, the authors do state that none of the treatments presented a very robust evidence base and that there are concerns over the quality of individual studies ³⁷.

In terms of pharmacotherapy, the NICE and NHMRC guidelines agree with the 2006 Cochrane interventional review among others ^{38, 39} that there is some evidence that some second-generation antipsychotics (aripriprazole and olanzapine) and some mood stabilisers (topiramate, lamotrigine and valproate) could improve BPD symptoms in the short term. However, for some of these agents, it is necessary to balance risks against benefits as they have considerable long-term risks (e.g. with antipsychotics, extrapyramidal side effects such as tardive dyskinesia can persist even after withdrawal of the drug ⁴⁰). Such risks are not a problem in psychological treatments and it is probable that this influences guidelines. In practice, off-label use of psychotropics is widespread, despite the fact that the NICE guidance negates their use. It is arguable that clinicians should preferentially use pharmacological treatments that have the strongest evidence base (i.e. antipsychotics and mood stabilisers) and refrain from using agents with the least evidence (i.e. antidepressants and benzodiazepines).

CONCLUSION

Specialist treatments, in particular DBT and MBT substantiate the use of psychotherapy in BPD and these findings support the validity of the NICE guidance. However, the array of such treatments must be amalgamated with the view to provide a comprehensive, multi-faceted treatment approach. Each treatment must be broken down in order to outline the components that are particularly useful in BPD with the view to understand the condition in greater depth and to provide more focussed therapies.

The 2013 Cochrane review ³⁷ highlights that further psychotherapies are available and have been shown to successfully treat BPD core pathology, however, as it is clearly stated the evidence base lacks robustness and there is a need for further studies that can replicate results. The therapies that have been included in this Cochrane review that have not been covered in the guidelines (e.g. STEPPS) may prove to be superior to those put forward by NICE, and I recommend that these be explored thoroughly when the guidelines are due for update.

While the NICE guidance emphasises that the use of psychotropics is reasonable in the management of comorbidities, it worth noting that to understand BPD, it is necessary to explore both the underlying aberrant psychological processes and biological processes that manifest in the disorder. This will enable the use of more specific pharmacological therapies in targeting the symptoms of BPD in the future.

Case Summary

Three and half year old male child presented to PICU, Narayana health BANGALORE, with a short history of fever of 8 days with headache  and  cough for 2 days. At admission the child was febrile, dull looking, haemodynamically stable with no meningeal signs or focal neurological deficit. He was admitted and evaluated for the cause of fever. Same day child developed generalized seizures along with fever, hence a possibility of meningitis or electrolyte imbalance (hyponatremia) kept as child had initial serum sodium of 128meq/l. The cause of hyponatremia was looked into and child managed with antiepileptic drugs and 3% normal saline infusion. The initial sepsis screen was in-conclusive and CSF analysis showed 3 lymphocytes with low glucose and elevated protein levels, hence partially treated meningitis was considered (as h/o admission to a hospital for 3 days prior to admission in our hospital). The antimeningitic dose of IV antibiotics were given.  On day 3 of admission child developed meningeal signs with worsening sensorium, hence  neuro imaging was done (MRI brain) which showed multiple well defined ring enhancing lesion at bilateral central and cerebrallar hemisphere, thalamus, pons with mild perilesional edema. This radiological picture suggested a possibility of nerucysticercosis, however the clinical picture did not match with the same, hence pediatric neurology opinion was taken and simultaneous workup for tuberculosis were started. Child was also started on IV steroid. A strong possibility of CNS toxoplasmosis was kept by neurologist based on radiological picture. The workup for TB was inconclusive (negative mantoux, normal ESR, negative gastric aspirate for AFB) however child was empirically started on category II ATT in view of deteriorating clinical state. Repeat CSF evaluation showed increasing cell counts and similar biochemical picture as before, the sample was also send for Gene-Xpert (DNA amplification study). On day 6 of admission child developed lethargy and drowsiness hence antiedema measures were initiated. Same day he developed tonic posturing with unequal pupil, hypertension and bradycardia indicating raised Intracranial pressure (ICP), for which he was intubated and ventilated and urgent repeat CT head was done which showed increase in ventricular size and hydrocephalus. Immediately EVD was put by neurosurgeons after which there was gradual improvement in child’s condition and he was extubated within 48 hours. The reports showed negative HIV and toxoplasma serology and positive CSF gene study for AFB confirming the diagnosis of CNS tuberculosis, hence ATT and antiedema measures were continued and the EVD was later converted into VP shunt. Child by 2^nd week of illness became afebrile with improved sensorium and function.

Fig 1 & 2: MRI showing multiple ring enhancing lesions

Discussion

Tuberculosis remains a leading cause of morbidity and mortality in the developing world. CNS involvement is thought to occur in 2-5% of patients with tuberculosis and up to 15% of those with AIDS related tuberculosis ^1,2. Although CNS involvement by tuberculosis is seen in all age groups, there is a predilection for younger patients, with 60-70% of cases occurring in patients younger than 20 years of age ^2. Haematogeneous spread from the lungs or gastrointestinal tract is most common, leading to small subpial or subependymal infective foci. These are termed Rich foci and form a reservoir from which intracranial manifestations may arise ^3,4. Tuberculomas often present with symptoms and signs of focal neurological deficit without evidence of systemic disease. The radiologic features are also nonspecific and differential diagnosis includes malignant lesions, sarcoidosis, pyogenic abscess, toxoplasmosis and cysticercosis.^5,6

Regarding treatment, the Center for Disease Control and Prevention recommends 12 months of treatment for CNS TB when the MT strain is sensitive to all drugs.⁷ However numerous variables can affect the response of the disease to therapy and it has been suggested that treatment duration should be tailored to the radiological response.⁸ After 12 months of treatment more than two-thirds of the patients still have contrast enhancing lesions. Although it is not clear if this represents an active lesion or just inflammation, continuing treatment is probably prudent. Total resolution of the tuberculoma is observed when scans demonstrate no enhancing lesions or only an area of calcification.⁸

In the case described above child had tubercular mengitis, multiple tuberculous, hydrocephalus and raised ICP. Although clinical presentations were suggestive of same, however the radiological picture and initial CSF finding raised suspicion is diagnosis. As tuberculoma and NCC shows many common clinical features, there are few distinguishing features such as the cysticercosis is smaller, less perilesional edema, multiple numbers and less of midline shift as compared to tuberculoma. However in our patient the multiple tuberculi gave a suspicion of NCC. It was only gene expert which confirmed our diagnosis.

Hence clinical cases like Tuberculoma, the radiological findings of which can usually be distinguished from other common illness like Neurocysticercosis or Toxoplasmosis, sometimes pose challenge in terms of radiological diagnosis suggesting the need for detailed evaluation to reach the diagnosis and guide treatment.

Introduction

Meningiomas are common intracranial neoplasms with a wide range of histopathological appearances. The WHO classification of tumours of the central nervous system recognises 15 subtypes of meningiomas, of which meningothelial, fibrous and transitional subtypes are most common. Lymphoplasmacyte-rich meningiomas (LPM) are rare WHO subtype that belong to Grade I meningiomas.¹ The estimated incidence is less than 1% of all meningiomas.² LPM usually occurs in young and middle age patients, with most common locations being cerebral con­vexities, skull base, parasagittal area within the superior sagittal sinus, cervical canal, optic nerve and tentorium.³ Histopathological examination shows extensive infiltrates of lymphocytes and plasma cells often obscuring the meningothelial component.

Case report

A 21-year-old man presented with a history of headache since 4 months. It was a dull pain not associated with vomiting, seizures or visual symptoms. The patient did not have any features suggestive of cranial nerve involvement. Physical examination was unremarkable except for the presence of papilloedema. Non-contrast CT scan showed a large isodense lesion with peri- lesional oedema and eccentric enhancing nodular component in the right fronto-parietal region (Figure 1). A radiological diagnosis of glioma with mass effect and shift to left was rendered. A right frontoparietal free bone flap craniotomy was performed. Operatively, a well encapsulated tumour probably arising from the dura mater was found. Gross total removal of the tumour was done and the excised tumour was sent for histopathological examination with a provisional clinical diagnosis of meningioma.

Histopathological examination revealed a tumour arranged as sheets and whorls of meningothelial cells without any mitoses or atypia. A dense infiltrate of lymphocytes and plasma cells was seen in large areas of the tumour (Figure 2).

On immunohistochemistry, tumour cells were positive for epithelial membrane antigen (EMA) (Figure 3) and vimentin. The lymphoplasmacytic infiltrate contained mixture of CD3 and CD20 positive lymphocytes. A diagnosis of lymphoplasmacyte- rich meningioma was given.

Figure 1. Non-contrast CT scan showing a large isodense cystic lesion with perilesional oedema and eccentric enhancing nodular component in the right frontoparietal region

Figure 2: Tumour arranged as sheets and whorls of meningothelial cells without any mitoses or atypia. A dense infiltrate of lymphocytes and plasma cells seen in large areas of the tumour (H & E x 100)

Figure 3: Tumour cells positive for epithelial membrane antigen (x 200)

Discussion

Meningiomas are common neoplasms accounting for 24-30% of all primary intracranial tumours. They arise from the arachnoidal cells, and are typically attached to the inner surface of the duramater.¹ Most of the meningiomas are benign, corresponding to WHO grade I and associated with a favourable clinical outcome. LPM is a rare low grade histopathological subtype of meningioma, usually seen in younger patients, with the mean age of onset being 34 years.^4,5 The patients with LPM have variable clinical manifesta­tions according to the location of the tumour. The common presentations include headache, hemiparesis, seizure, vomit­ing, dizziness, visual disturbance, dyscalculia, dysgraphia and slurred speech.³ Although the natural history of LPM is often over one year, few cases might occur in short duration due to inflammatory cell infiltration and oedema.⁶ Systemic haematological abnormalities such as hyperglobulinemia and iron refractory anaemia have been documented in some patients with LPM, believed by some to be due to the plasma cell infiltrate.^3,6,7

Radiologically, LPMs are usually globular, highly vascular, contrast- enhancing, and dural based tumours. The typical characters of LPM on MRI are isointense lesions on T1-weighted images and hyperintense lesions on T2-weighted images, with a strong homogenous enhancement after the administration of gadolinium; obvious peritumoural brain oedema and dural tail signs.³ Sometimes, cystic component and heterogeneous enhance­ment may also be encountered, making pre­-operative diagnosis difficult, as in our case.⁸

On microscopic examination, this tumour is characterised by a conspicuous infiltrate of lymphocytes and plasma cells, sometimes completely obscuring the tumour cells. The massive infiltration of lymphocytes and plasma cells has been postulated to play a central role in the development of brain oedema associated with LPM. The origin of this tumour (neoplastic or inflammatory) is unclear, so it is considered closer to intracranial inflammatory masses rather than typical meningiomas.⁷