Sep

Background.

Processed sugar has a high glycaemic index (GI) as it is easily digested and absorbed triggering a prominent insulin response, which if repeated over time leads to insulin resistance and type two diabetes^{1, 2}. The appealing nature of high calorific sugary food combined with their low satiating nature means they also tend to be eaten in excess which contributes to obesity and metabolic syndrome^{2, 3}. Obesity and diabetes raises the long-term risk of poor gut health and chronic inflammation increasing the risk of chronic fatigue, low mood and degenerative disease conditions such as cancer, cardiovascular disease, dementia and stroke^{2, 3}.

Despite these obvious risks, a recent survey of NHS health care professionals reported that over half are overweight and over a quarter are living with obesity⁴. Both obesity and high sugar content-foods are associated with musculoskeletal disorders, lower mood, unhappiness, fatigue and depression which significantly contribute to sickness absence from work^{4, 5, 6, 7.}

Despite these risks, consumption growth continues to escalate especially in low and middle income countries. Since 2000 consumption has grown from 130 to 180 million tonnes in 2020⁸, and its production is contributing to poor health as well as greenhouse gas emission and deforestation^{9, 10}.

In an attempt to reduce sugar intake, NHS England introduced a voluntary reduction scheme in July 2017, recommending that NHS Trusts and retailers on NHS premises reduce the proportion of monthly sugar-sweetened beverages sales. They reported in March 2018, a reduction as a proportion of total drinks sales from 15.6% to 8.7%¹¹. However, to date, there is no information as to whether this has had any impact on consumption of sugar, wellbeing or weight reduction. In our cancer unit there is a constant availability of sweet snacks, predominantly gifted by patients, and during busy clinics these often replace balanced meals. Some argue that this display of sugary foods, together with the high proportion of overweight staff undermines the NHS’ ability to give patients ‘credible and effective’ behavioural lifestyle advice.

The hypothesis for this intervention was that a removal of sugary foodstuffs from the field of vision on nurses’ stations and replacing with fruit, nuts and seeds enables healthy snacking, resulting in weight loss and increased mood.

Methodology

This pilot intervention used quantitative methods to observe the feasibility of delivery and outcome of a real-world intervention. This project was registered with and approved by Bedford Hospital NHS Trust Research and Development Department, but classed as a practical service evaluation, hence no Ethics approval or written consent was required.

Participants: Fifty eight members of staff at the Primrose unit, Bedford Hospital were invited to participate for this 3 month nutritional intervention; 44 (75%) volunteered. The cohort consisted of 36 nurses, 2 consultants, 2 secretaries and 4 administration staff. There were 41 females and 3 males, aged 28-72 years (average age 45 years). A further 100 consecutive patients attending for treatments were asked for their views on the intervention.

Measures and outcomes: The primary endpoints were Body Mass Index (BMI) (Kg/m²) and happiness measured with the previously validated Subjective Happiness Score (SHS)¹². As a secondary end point, patients attending the Oncology unit during the intervention period were asked anonymously for their opinion and likely influence on their eating habits.

Procedure: At baseline the Primrose Unit research department recorded staff demographics, BMI and SHS questionnaire scores. From the date of entry of the first participant (June 2019) to completion of the last participant (September 2019), all sugary foodstuffs were removed and replaced with bowls of mixed whole and dried fruit, seeds and mixed nuts. Non-participating staff were asked to voluntarily keep sugary items out of general sight. At baseline, 3 months and 5 months, participants were weighed by one of the research team and completed a SHS questionnaire.

In the final month of the intervention, 100 consecutive patients attending for treatments at the unit were asked their opinion of this intervention, specifically if they felt that removing sugary items from public display was a welcome gesture and whether seeing staff making efforts to reduce sugar intake would encourage them to do the same.

Statistical methods and analysis

The completed dataset was compiled in an excel spreadsheet then transferred for independent statistical analysis. The pre- and post-intervention weight differences datasets were analysed by the T-test as were the difference in happiness scores. The differences in participants’ opinion were analysed by the chi squared test. There were no missing data and in view of the relatively small numbers in the cohort, sub-group analysis was not planned or performed. The study advisory committee predetermined that a change in weight of 1 kg was meaningful¹³.

Results

Average weight: At baseline the average was 72.12 kg, and 71.23 kg.at 3 months; an average loss of 0.89 kg (T-test p= 0.02). The average weight at 5 months was 71.09 kg; an average loss of 1.03 kg from baseline (T-test p= 0.01). Twenty participants (46%) lost >1kg in weight (average 3.01 kg) as opposed to 7 (16%) participants who gained >1kg (average 2.23 kg) T-test p< 0.03.

Happiness score: Average happiness score increased from 21.65 to 23.44 (+6.6%), T-test p< 0.04). Amongst those who lost >1kg weight, average happiness score increased from 21.54 to 23.75 (+9.3%), T-test p<0.03. In those who gained >1 kg weight, average happiness score decreased from 22.28 to 21.43 (-3.8% T-test p< 0.08. There was a 13.1% difference in the happiness score in those losing >1kg compared to those gaining >1kg in weight (p< 0.001).

Patient opinion: 94 (94%) of patients indicated that this initiative gave a good impression; 6 (6%) were not sure or felt it did not give a good impression (Chi²p<0.001). Ninety seven (97%) indicated that the initiative would encourage them to reduce sugar in their own diet versus 3 (13%) who were not sure or felt that it would not change their behaviour (Chi² p<0.001).

Discussion

This small pilot evaluation has a number of methodological weaknesses but what it lacked in statistical strength it gained in novelty and potential importance. This was the first nutritional intervention involving hospital staff within a routine working practice. It addresses a health issue which affects hundreds of thousands of health workers every year, and demonstrated that a practical behavioural change initiative was welcomed by the majority of staff (75%), with no drop-outs or objections from non-participating staff. This implied a larger national study would be feasible.

These data clearly demonstrated a statistically significant reduction in meaningful weight similar to the best designed weight loss programmes¹⁴. A fundamental rule of behavioural change is not to dictate to people, but to encourage them to want to make the decision to change for themselves. This simple intervention did not stop staff eating what they wanted as there was no restriction to their overall food choices. The big difference was that, within their field of vision, there were healthier fruit and nuts instead of high-calorie, sugar-laden foods, which are usually readily available.

This intervention was overwhelmingly supported by patients. Surveys have repeatedly reported that patients look to health workers for guidance, and this study confirmed that this manoeuvre made patients think about their own eating habits. Although a further trial would have to establish whether this initiative objectively reduce processed sugar intake amongst patients, a reduction in intake would confer considerable benefits as several large cohort studies have linked high sugar intake with a higher risk of cancer, greater complications of treatments and worse outcomes, for several reasons³.

Sugary foods increase the risk of weight gain, already more common after cancer; increases levels of oestrogen in post-menopausal women; and increases insulin like growth factor (IGF) and other hormones such as leptin, all of which in laboratory experiments increase proliferation and markers of aggressiveness and spread of cancer cells ^{2, 15, 16, 17}. Cohort studies have also reported that those who ate more than 10% of their daily calories as sugar had higher total LDL cholesterol levels further adding to the cardiac risks of herceptin and anthracycline chemotherapy drugs. Independent from obesity, high sugar intake directly increases the risk of type 2 diabetes (T2D) by overloading the insulin pathways¹. Individuals with T2D have higher serum insulin levels (hyperinsulinemia) which triggers proliferation in cancer models¹⁸, is linked to higher oxidative stress and low-grade chronic inflammation, causing epigenetic genetic damage and ongoing malignant transformation¹⁹. These laboratory findings are supported by several cohort studies which have linked diabetes with a higher risk of cancer and a higher risk of relapse post-treatment²⁰.

Patients on chemotherapy should be particularly discouraged from eating sweets and cakes as they are more prone to dental caries which contributes to the risk of osteonecrosis following consequent bisphosphonate therapy. Dental caries may also be an increased factor for bowel cancer itself as DNA codes from bacteria, commonly found in caries (Fusobacterium), have been detected in the genes of bowel cancer but not in normal guts²¹.

Patients receiving the new generation of targeted therapies should be particularly vigilant of their sugar intake. PD-1 inhibitors recruit the body's immunity to recognise and target cancer cells, the influence of diet and lifestyle is becoming even more important. Studies have demonstrated that better gut health is linked to significantly better response rates. Processed sugar is the preferred fuel for pro-inflammatory firmicutes bacteria whilst the healthy bacteroidetes utilise glycans from the breakdown of polyphenols, which explains why there is a reverse correlation between sugar intake and gut health²². However, whole fruit intake is associated with better gut and general health as it provides polyphenol which feed healthy bacteria^{3, 23}. Despite having between 9-14% fructose, the fibre and pulp makes fruit satiating and slows gastric emptying, thus reducing the GI³. Additionally, the polyphenols in fruit, vegetables, nuts, legumes, herbs and spices slow transportation of sugar across the gut wall by inhibition of sodium-dependent glucose transporter 1. They enhance insulin-dependent glucose uptake, activate 5' adenosine monophosphate-activated protein kinase, which explain why their regular consumption is associated with a lower risk of T2D^{3, 23, 24}. They also improve reduced gut and systemic inflammation; enhance anti-oxidant enzyme production so reduce intracellular oxidative stress; and reduce the risk of cancer and other chronic diseases including those associated with diabetes^{3, 25, 26}.

The evaluation was not robust enough to measure whether this resulted in less sickness absence, but this endpoint should be included in a larger design. It also did not include data for those staff who did not actively participate, but who benefited from removal of sugary foods from their work areas; the evaluation committee did not receive any complaints or objections to their removal.

Government initiatives such as a sugar tax and public information campaigns may help but as individuals within the NHS, we have an opportunity to influence our staff, the patients whom we serve and the wider public. The evaluation reported in this paper is a small start, but demonstrates that a multicentre study would be feasible and if the results are confirmed, it could initiate a national cultural change attitude towards sugar in the NHS.

Background

Depression and osteoporosis are two extremely common comorbidities in geriatric patients. Each have their associated mental and physical impacts on the patient, and economically on the wider healthcare system. Staggeringly, up to 39% of frail patients suffer with depression.¹ Selective serotonin reuptake inhibitors (SSRIs) have long since been used in the management of depression and anxiety states and are one of the fastest-growing classes of drugs prescribed. Their use is not without the potential for negative effects; their side effect profile includes nausea, anxiety, insomnia, sexual dysfunction and gastro-intestinal upset, with the impact on bone mineral density (BMD) being controversial.

Statistics from the International Osteoporosis Foundation (IOF) reveal that in 2015, 6.8% of men and 21.8% of women over the age of 50 had osteoporosis. The estimated lifetime risk of hip fractures for women over 50 is 17.2%, with fracture-related costs at 5.3 billion pounds in 2017.² Osteoporosis is a progressive, systemic skeletal disorder characterised by loss of bone tissue and disruption of bone microarchitecture, that leads to increased bone fragility and consequently an increased risk of fracture. As well as increasing age and female sex, other well documented risk factors for reduced BMD include early menopause, alcohol use, corticosteroid use, smoking, sedentary lifestyle, low body weight, impaired eyesight, and recurrent falls. What is more, depression itself cannot be overlooked as a risk factor for osteoporosis.

The mechanism by which depression leads to lower BMD is by that of alternation of the hypothalamic-pituitary-axis system, resulting in hypercortisolism. Cortisol is a well-known factor in bone loss. Proinflammatory cytokines have been implicated in depressive disorders, and they may directly stimulate osteoclastic activity.³ What must also be considered is the impact that depression has on certain lifestyle choices such as the potential for increased alcohol and nicotine consumption, inadequate nutrition and low physical activity.

The presence of serotonin receptors, neurotransmitters, and transporters have been found within osteoclasts and osteoblasts.⁴ 95% of serotonin is synthesised in the gut and cannot cross the heteroencephalic barrier. Gut derived serotonin reduces osteoblast proliferation, thereby leading to bone loss. Brain derived serotonin signals to the ventromedial hypothalamic neurones leading to decreased sympathetic output and therefore favours bone formation by action on the beta-2 adrenergic receptors on the osteoblasts. It appears that with shorter duration of use, decreased bone resorption predominates, and with longer term use, bone loss outweighs.⁴

The impact of SSRIs on bone health has long since been the subject of research, with a possible link with both increased risk of fractures, and reduced bone mineral density being identified. In response to emerging evidence, the MHRA issued advise to healthcare practitioners, stating that we “should be aware of epidemiological data showing a small increased risk of fractures associated with the use of TCAs and SSRIs, and should take this risk into account in discussions with patients and in prescribing decisions”, yet this has not yet filtered down to prescribing guidelines.⁵ The National Institute for Health and Care Excellence (NICE) guidelines state that on choosing the antidepressant to prescribe, healthcare practitioners must consider that there is currently no evidence to support using specific antidepressants for specific physical health problems.⁶

We therefore present a case of recurrent depressive disorder in a patient with a background of osteoporosis. We also include a review of the most up-to-date literature, with the aim of increasing awareness of the impact of SSRIs on bone health for fellow prescribers. We aim to highlight the difficulties we face as clinicians whilst there are no formal recommendations regarding the use of SSRIs in high risk populations.

Case Description

This 78-year-old was referred to our services in late 2019 with low mood and loss of motivation. She lives alone following the death of her husband 3 years ago and sadly has no family. She has a past medical history of depression, hypertension, acute pericarditis, subclinical hypothyroidism, hiatus hernia, cataracts, previous cholecystectomy, and osteoporosis.

She was diagnosed with osteoporosis in 2000. At that time, she had been seeing an osteopath due to back pain, who advised her to see her GP to investigate for arthritis or osteoporosis. She has a family history of osteoporosis on her mothers’ side. She was diagnosed by Dual-Energy X-ray Absorptiometry (DEXA) scan, with osteoporosis at the lumbar spine and pelvis, at which time she was started on calcium supplementation.

She was initially started on oral alendronic acid but developed reflux symptoms, so this was discontinued. Over the following years she was tried on various medications for bone protection but sadly developed side effects. Briefly, pamidronate infusion caused iritis, and nausea was reported whilst on sodium ranelate. Later she was to be commenced on sodium risedronate, however did not start this due to concerns she had following reading the information leaflet. Denosumab was discussed as the next suitable option, however she was undergoing dental work including tooth extraction and so this has been delayed due to the risk of avascular necrosis of the jaw.

DEXA scanning in March 2019 showed a T score of -0.8 at the neck of femur, -4.5 at the forearm, -1.3 at the total hip, and -4.2 at the spine. This had, unsurprisingly, worsened from her last DEXA in 2016 (-3.6 at the spine). Her risk of major osteoporotic fracture was last calculated at 21.6%, with the risk of hip fracture 11.5%. She has had no falls or fractures to date since her diagnosis.

Other than Adcal-D3 she is now no longer on bone protection. Her current medications also include levothyroxine, ramipril, bisoprolol, cetirizine, fluticasone nasal spray, and Hypromellose eye drops.

She had initially been started on citalopram by her GP which she had discontinued herself after a period of weeks as she felt it had no positive effect. In December 2019 she scored 92/100 on the Addenbrooke’s Cognitive Examination (ACE-III), with no significant deficits in any one category. As well as low mood and loss of motivation, she described frequent tearfulness, anhedonia, lack of energy, difficulty concentrating and poor sleep. There was no clear trigger for her current mental state, and her physical health was otherwise good. She had no suicidal ideation or thoughts of self-harm. There was some evidence of anxiety but no symptoms of psychosis. We could not identify any alcohol or substance use risks. Her mental state examination was unremarkable. She was given the diagnosis of moderate depressive episode, F32.1, and was started on sertraline. However, upon reading the patient information leaflet, she refused to start this medication due to it mentioning a link with bone disorders.

As a result of this discussion, we accessed the medicines.org patient information leaflet, where an increased risk of bone fractures is mentioned under the heading ‘symptoms that can occur when treatment is discontinued’. It also states that following clinical trials in adults, sertraline was found to cause ‘bone disorder’ in up to 1 in 1,000 people.⁷

Following in-depth discussions, our patient was very hesitant in agreeing to take any medication that may have an impact on her bone density. We were aware of the potential association between SSRIs and BMD but were unable to quantify this risk to our patient.

Discussion

Our case above represents a common situation; a patient that is worried about a side effect, concerning which there are no formal guidelines available to aid decision making. The link between depression, SSRIs and BMD is a complex one, with numerous confounders making analysis and application yet more difficult. We looked at the evidence surrounding SSRIs and their impact on bone health, in order to suitably advise our patient on the most appropriate treatment options.

Impact on BMD

We found several meta-analysis and systematic reviews concerning BMD. The majority showed no significant association between BMD and SSRI use.

Of note, a 2015 systematic review by Gebara et al, suggested that antidepressant use may well be associated with lower BMD. 4 of the included studies assessed the relationship with BMD, 3 of which highlighted an association with lower BMD. This association was reported with SSRIs but not TCAs. However, they concluded that there was insufficient evidence that SSRIs adversely affect bone health, and therefore a change in current recommendations for the use of antidepressants in older adults was not justified at the present time. They stated that the evidence did not satisfy the Bradford Hill criteria, it is inconsistent, and whilst there is biological plausibility, there are no experimental studies to support a causal relationship.⁸

Yet a 2012 literature review indicated effects on both BMD and fracture risk.⁹ Each and every study included, indicated a risk of reduced BMD, increased fracture risk, or both. Even when controlling for potential confounders this conclusion was drawn. Authors suggested on the basis of this evidence, that caution is advised when considering the use of SSRIs in those with osteoporosis or a history of osteoporotic fractures, despite there being no formal recommendations.

A 5-year longitudinal study involving 1988 women, 319 of which were using antidepressants, measured femoral neck BMD. A dose-response increase in bone mineral loss was evident.¹⁰ An older cohort study also showed that even after adjustment for potential confounders, mean total hip BMD decreased 0.47% per year in non-users, compared with 0.82% in SSRI users.¹¹ A year later, and a community-based study revealed that after controlling for age, weight, height and smoking history, BMD among SSRI users was 5.6% lower at the femoral neck, 6.2% lower at the trochanter and 4.4% lower at the mid-forearm than nonusers.¹²

Fracture Risk

The evidence surrounding fracture risk is more unanimous. Of the systematic reviews and meta-analyses we found, all highlighted an increased risk of fracture in SSRI users.

Wu et al concluded that the significantly higher risks of fractures observed for patients who received SSRIs compared with patients with no exposure, remained statistically significant in studies that controlled for important risk factors and studies that scored highly in the quality assessment.¹³

Eom et al extrapolated their data, estimating that the increased risk of fractures translates to about one case of fracture for every 42 patients treated with SSRIs.¹⁴ The dose and duration of SSRIs also seems to contribute to fracture risk, with both an early increased risk (under 6 weeks), and a late risk associated with prolonged use.^14,15

A notable literature review by Panday et al on medication-induced osteoporosis summarised that treatment decisions concerning SSRIs should be considered on an individual basis for patients with osteopenia, osteoporosis, or fracture risks greater than 3% and 20% for hip and major fractures respectively.¹⁶ Of particular note from this review, a 10-year cohort study revealed that 14.7% of SSRI users suffered at least one fragility fracture over the study period.¹⁷ Whilst those using SSRIs do tend to have more fracture risk factors than the general population; they are more likely to be women, have more comorbidities, use other antidepressants/ anxiolytics, and have a previous history of falls; the significant association remained even after these variables were controlled for. The risk of first fracture specifically was increased by more than 50%, and similar to other studies, a dose–response relationship was evident.¹⁷

Conclusion

The impact of SSRIs on bone health is clearly a topic of contention. Whilst the impact on BMD is unclear, the increased fracture risk is more unanimous. There are plausible biological mechanisms to explain these risks, yet there is also the fact that the risk of falls themselves are higher when taking SSRIs.

Yet why hasn’t this filtered down to making formal recommendations in prescribing guidelines? Questions remain as to whether we should be prescribing SSRIs in individual’s with osteoporosis at all. Regardless, the relatively high risk of fracture with SSRI use may have a significant clinical impact. These risks must be balanced against the benefits gained by the treatment for depression; both in terms of mental state and in osteoporosis risk factor modification. What would perhaps be more relevant would be to consider a patient’s falls risk independently to their bone health, when deciding whether to prescribe SSRIs. Consideration towards the use of concomitant medications, co-morbidities and other confounders is vital.

It is on this basis that we suggest discussing bone health with your patients (particularly those at high risk), prior to prescribing these medications, and being wary of prescribing SSRIs in those with osteoporosis or more importantly, those at high risk of falls.

Introduction

Insomnia is a disturbance of normal sleep patterns. It is characterised by sleep onset latency and/or sleep maintenance. Short term insomnia is defined as having symptoms for less than four weeks, whilst long term insomnia is symptoms lasting more than four weeks¹. Hypnotics can provide relief from the symptoms of insomnia; they do not treat any underlying cause.

Several hypnotic agents are licensed for the treatment of insomnia, including the benzodiazepines and Non-benzodiazepine hypnotics (Z-drugs⁾².

NICE guidance for Insomnia management states “After consideration of the use of non-pharmacological measures, hypnotic drug therapy is considered appropriate for the management of severe insomnia interfering with normal daily life; it is recommended that hypnotics should be prescribed for short periods of time only, in strict accordance with their licensed indications” ¹.

NICE guidance also advises to use the lowest effective dose of the hypnotic agent for the shortest time frame possible. The exact duration will depend on the underlying cause, but treatment should not continue for longer than two weeks. We should also inform the patient that further prescriptions for hypnotics will not usually be given, ensure that the reasons for this are understood, and document this information in the patient’s notes.

Side effects are common with hypnotic usage including, most importantly, the development of tolerance and rebound insomnia. Other side effects can occur such as daytime sedation, poor motor coordination, cognitive impairment, hallucinations, anxiety, delusions and sleep disorders².

Aims

To reduce the amount of hypnotic medication being prescribed to patients on an Acute Inpatient psychiatric ward in the Northwest of UK. The ward is in a semirural psychiatric hospital and is a Male ward containing 17 inpatient beds. The patients are 18 years old onwards with varying diagnosis including Generalised Anxiety Disorder, Bipolar Affective Disorder, Schizophrenia, Depression, and patients with mental and behavioural disorders due to psychoactive substance use.

The reason for doing this project was most importantly for improving patient safety by reducing unnecessary prescriptions and therefore administration of hypnotic medications, but also to reduce NHS expenditure and carbon footprint.

Inclusion criteria

Patients who have been an inpatient on the selected ward between the 09/12/2020-20/01/202 and 28/01/2020-10/03/2020.

Intervention

We developed a prescription aid flow chart (Appendix 1) for all newly admitted patients to the ward. This will guide doctors when making the decision if a hypnotic prescription is warranted.

All patients on the ward during this intervention period, who are currently on a hypnotic agent and are not newly admitted, will have their hypnotic prescription reviewed using the flow chart (Appendix 1) at their weekly consultant ward round.

We then decided on some interventions to fulfil our aims. The interventions were as follows:

1) Development of an educational presentation about Insomnia and sleep management.

2) Development of an Insomnia management Flow chart (Appendix 1) to be used at admission point.

3) Training sessions for ward staff.

4) Shared teaching programme with patients at their sleep management sessions.

5) Face to face and E-mail correspondence to inform medical trainees about this project.

6) Gather feedback from ward patients and staff before and after this project.

The Hypnotic prescription flow chart aid (Appendix 1), has been put on the ward office notice board, the clinic room and the On Call Doctors Room. It was also e-mailed out to the regular ward doctors, as well as all on-call doctors working during the intervention period.

As discussed above, we created an educational PowerPoint presentation entitled “Insomnia and hypnotic agents”. This included insomnia definitions and types, NICE guidance on insomnia, sleep hygiene advice, the medications used for insomnia, their mode of actions, side effects, cautions and cost of these medications. We also included our new hypnotic prescription flow chart aid (Appendix 1).

From the 21/01/2020-27/01/2020 we had two of these educational training sessions. This was to ensure that all staff working on this ward attended at least one of these sessions. Staff in attendance included the ward managers, nursing staff, health care assistants, the pharmacist, a junior doctor, and the ward consultant. This was very important as all these health care professionals are involved with the management of patients on the ward, and those suffering from insomnia. We felt that this session was vital as we wanted to ensure that all the staff knew the importance of this project and could raise their own concerns and issues that they have with regards to managing patients with insomnia. This proved to be very useful as we all brainstormed and voiced some realistic ward changes that could happen on an inpatient psychiatric ward. We also acknowledged that sleeping on the ward as an inpatient can often be disturbed, due to regular nursing checks and noise from the staff and other patients. We did however discuss some feasible interventions which included:

1) The time at which all the automatic ward lights are turned on in the morning could be delayed.

2) Caffeine –free coffee/tea available only after a particular time in the evening.

3) Discourage daytime napping.

4) Have regular sleep-hygiene sessions on the ward.

Between 28/01/2020 to the 10/03/2020 we started these interventions, and this is the time period for collection of our next six weeks of data. We had multiple patient group sessions on sleep hygiene during this time led by the occupational therapist. Other health professionals assisted with this, including the ward pharmacist and the junior doctor. During these sessions we asked for patients to give their feedback on the current management of insomnia on the ward. Some responses included:

· One patient with Severe Generalised Anxiety Disorder stated that he feels that the sleep hygiene advice is helpful, as he doesn’t like to “jump straight into taking tablets” and likes to “fix the root” of his sleeping problem.

· A second patient with a diagnosis of Mental and Behavioural Disorder due to use of cannabinoids, stated that he needs both sleeping medications and sleep hygiene advice, as sometimes he still cannot get to sleep on the ward by solely using relaxation methods.

· A third patient with Generalised Anxiety Disorder stated that he found the sleep hygiene sessions useful. He is now using relaxation methods and is trying to avoid daytime naps which are both helping with his sleep. However, he still on occasions struggles with sleep. He said it is important to have a tidy, clean and relaxing sleeping environment, which is sometimes difficult to implement on the ward.

Appendix 1

Results:

Data was collected prior to any intervention on the ward between the dates 09/12/2020 and 20/01/2020.

The table below (Table No.1) includes the type and number of sleeping tablets prescribed on the ward between the dates 09/12/2020 and 20/01/2020. The total number of patients treated from 9 December 2019 to 20 January 2020 were 28 and the total number of patients were prescribed hypnotic medication during this time were 14.

Table No.1 - Hypnotic medication prescribed:

The table below (Table No.2) includes the number of hypnotics prescribed and administered after the interventions mentioned above. The total number of patients treated from 28 January 2020 to 10 March 2020 were 25 and the total number of patients who had prescribed hypnotic medication were 11.

Table No. 2- Hypnotic medication prescribed:

With our ward interventions we have significantly reduced the amount of hypnotic tablets being administered. The total number of tablets administered during this 6 week period was 102. The total number of patients who were prescribed hypnotics was 11. Prior to our interventions the total number of tablets administered between 9^th December 2019 and 20^th January 2020 was 224 and 14 patients in total were treated. This demonstrates a 44.5% reduction in tablets which is significant.

Discussion

The total reduction in tablet administration was very significant with a 44.5% reduction post-intervention. This demonstrates the positive change in our clinical practice that has resulted from using the flow chart aid (Appendix 1) as well as patient and staff educational and feedback sessions. This will improve patient safety by reducing the risk of side effects. The risk of patients developing tolerance to hypnotic medications has been reduced, as well as reducing those being discharged on a regular prescription which will further improve long term expenditure of hypnotic medications for the NHS. With the changes that have occurred in our clinical practice, we have reduced the number of hypnotics being unnecessarily prescribed and administered.

Over prescribing/unnecessary prescribing is an issue within the NHS and is impacting negatively on the environment. The NHS constitution states that the NHS is ‘committed to providing the most effective, fair and sustainable use of finite resources’³. By reducing the number of inpatients being unnecessarily started on hypnotic medications, another positive from this project will be the reduction in the negative pharmaceutical impact on the environment. The number patients being discharged with hypnotic medications, who may no longer need them, due to their insomnia improving when they are discharged from the inpatient setting will also improve. Furthermore, if they are unnecessarily started on a hypnotic prescription as an inpatient, they may continue this prescription regularly and become tolerant, which will inevitably have an undesirable effect on the environment.

The feedback that we received from the educational insomnia teaching sessions also proved to be very useful. As stated above the staff sessions allowed us to brainstorm simple ward-based interventions, as well as discussing possible drawbacks which may result. This allowed us to modify the flow chart so that it worked for all staff effectively.

The feedback given from patients was also very encouraging. As health professionals we sometimes overlook how some patients want and need more involvement in making decisions on aspects of their care. Ensuring patients are informed about medications prior to prescribing, especially about side effects is something that is very important and allows patients to make informed decisions which is a more holistic approach to clinical practice. This is vitally important prior to prescribing any medications but especially medications with more severe side effects which some hypnotics have.

The patient educational sessions were a key part of this project. We gathered feedback and established that the patients involved found these sessions informative. Some, but not all, of the sleep hygiene advice was feasible to implement into their daily routine on the ward. The ward can be disruptive at night, due to other patients, or due to regular staff checks in patient rooms, as well as rooms not being familiar surroundings, were two of the difficulties raised from the patients. This is something that we appreciate can’t be changed, however with the interventions that can be feasibly made on the inpatient psychiatric ward, we continue to strive to implement and improve for patients. For these reasons both the staff and the patient educational sessions should be continued and proved a vital part of this project

Following on from this initial intervention, we feel that we can continue to make further changes and expand the changes we made on this ward, to other similar wards in our hospital and to other inpatient psychiatric wards in the Trust.

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

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.

Introduction

Multiple Sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) that affects approximately 400,000 people in the United States and 2.5 million worldwide.¹ There are rare variants of this disease that can profoundly delay diagnosis and treatment. Examples of such variants include: Tumefactive MS, Acute Disseminated Encephalomyelitis, Neuromyelitis Optica, Marburg’s MS and Balo Concentric Sclerosis.² These variants have a uniquely aggressive presentation and do not exhibit classic MS features.² Classic MS features include relapsing and remitting sensory and motor impairments, optic neuritis and pain. These aggressive variants are more likely to present with symptoms similar to neoplasm such as motor impairments and seizures. When dealing with these aggressive MS variants diagnostic options include Magnetic Resonance Imaging (MRI), Single Photon Emission Computed Tomography (SPECT) scan, MR spectroscopy and Cerebrospinal Fluid (CSF) analysis.³

Invasive tests such as brain biopsy are not warranted unless absolutely necessary. In MS, a biopsy must not be completed in order to confirm a diagnosis. However, to confirm a diagnosis of cancer a biopsy is required.

We present a rare case of Tumefactive MS that exhibited a clinical picture identical to brain metastasis. This was diagnosed with surveillance MRI and CSF analysis in the absence of a brain biopsy.

Case presentation

A 48-year-old African American female was brought in by emergency medical services after falling with a brief loss of consciousness. Associated symptoms included dull chest pain, diaphoresis and shortness of breath. While in the emergency department she also developed nausea, vomiting and dizziness. The patient reported no similar previous episodes and denied precipitating events. There was nothing else to note on review of systems. The past medical history included hypertension with no previous surgeries and family history included breast cancer of the mother diagnosed at age 47. The patient denied tobacco, alcohol and intravenous drug use. She noted an allergy to iodine.

On physical examination the patient was afebrile, normotensive and tachycardic with an oxygen saturation of 89% on room air. She was alert and oriented but pale and diaphoretic with mild left sided chest pain. Cardiac examination revealed a normal rhythm tachycardia and no murmurs were heard. Her neurological examination showed a normal mental status, normal cognition/comprehension and that Cranial Nerves II-XII were intact.

Laboratory findings included haemoglobin of 9.8 g/dL, 30.8% haematocrit and potassium of 3.3 mmol/L. Electrolytes were otherwise normal. Cardiac workup showed a normal ECG and slightly elevated cardiac enzymes of 0.319 ng/mL.

Given the patients tachycardia and desaturation, a stat Ventilation-perfusion (V/Q) scan was completed (patient had an iodine allergy). The V/Q scan revealed a perfusion defect suggesting pulmonary embolism (PE) as the cause of symptoms. Subsequently the patient was placed on appropriate anticoagulation.

Head CT (computed tomography) showed a left centrum semiovale round hypodense lesion measuring 1.4 cm, a left basal ganglia round hypodense lesion measuring 1.0 cm and a left occipital lobe round hypodense lesion measuring approximately 1.0 cm (Figure 1). No midline shift was seen. MRI showed multiple hypointense T1/hyperintense T2 nonenhancing lesions, mainly within the left cerebrum (Figure 2 A-F). The three largest lesions within the left posterior centrum semiovale (2A), left globus pallidus (2B) and left posterior corona radiata adjacent to the occipital horn (2C) measured 1.5 cm, 1.0 cm and 1.0 cm respectively. Perilesional vasogenic oedema was seen in all except the basal ganglia lesion. There were bilateral cerebral scattered foci of hyperintense FLAIR/T2 signals (D-F). The imaging suggested a differential diagnosis which included metastasis, infection or primary CNS malignancy.

Further work up in search for possible malignancy was completed. Skin map revealed no concerning nevi. Mammogram showed no tumor. CT of the abdomen and pelvis revealed a 2.6 cm indeterminate hypodense lesion in the left lobe of the liver (Figure 3A) along with an enlarged fibroid uterus (17x 7 x 14 cm). Liver biopsy was considered but a repeat MRI and ultrasound showed the lesion to be cystic, so this was deferred following surgical oncology recommendations (Figure 3B). For the hypertrophic uterus found on imaging, gynecology felt no further workup was necessary as they attributed the findings to a fibroid uterus.

Tumor markers CA 27-29, CA 19-9, CA 125 and AFP were all sent and came back negative. Initial lumbar puncture with CSF analysis was not completed secondary to possible complications that could be incurred while on necessary PE anticoagulation.

Due to a non-focal neurological examination, she was discharged on Levetiracetam 500 mg for seizure prophylaxis and Dexamethasone 4 mg for perilesional oedema. Over subsequent months the patient did well without headaches, vision changes or seizure like activity. On subsequent visits to the clinic, she had no evidence of focal neurological deficits except for mild bilateral symmetric hyperreflexia. Given that the metastatic work up remained negative, we considered obtaining a baseline Positron emission tomography (PET) scan to ensure we were not missing any possible metastasis.

She subsequently went back to work full-time and reported no symptoms. Repeat MRI of the head (Figure 4 A-C) showed predominantly T1 hypointense and T2 hyperintense (A-B) lesions with significant decrease in size from MRI done three months ago. These lesions demonstrated no enhancement to incomplete ring enhancement, with diminished vasogenic oedema (A). These findings suggested an inflammatory demyelinating process so a lumbar puncture was obtained after anticoagulation was held. CSF analysis was done using Isoelectric Focusing (IEF) and immunoblotting methodology. This revealed a normal myelin basic protein but with eight oligoclonal bands restricted to the CSF. These findings solidified the suspicion of Tumefactive MS.

Figure 1. Head CT without contrast: left centrum semiovale round hypodense lesions measures 1.4 cm with perilesional vasogenic edema

Figure 2. MRI of brain showing axial T1-weighted (A-C) hypodense lesions of the left centrum semiovale(A), left basal ganglia(B) and left occipital lobe(C). Axial T2-weighted (D-F) views show multiple hyperdense lesions corresponding to the same locations. Perilesional vasogenic edema is seen.

Figure 3A. Thorax CT without contrast. 2.6 cm left lobe liver lesion.

Figure 3B. MRI of abdomen showing coronal T2-weighted half-Fourier acquisition single-shot turbo spin-echo (HASTE) hyperdense lesion. A mildly enlarged liver measuring 18.7 cm in craniocaudal span. Simple 2.8 x2.4 cm cyct in the medial segment of left lobe.

Figure 4. MRI of brain (3 month after initial scans) showing axial T-2 weighted (A-B) hyperdense lesions of the left centrum semiovale(A) and left basal ganglia(B). There is irregular peripheral enhancement. Considerable decrease in size is seen from previous MRI (Figure 2). Left posterior centrum semiovale, left globus pallidus and left occipital lobe lesion measure 1.3 cm, <1 cm and <1 cm respectively. Vasogenic edema is diminished in comparison to previous study.

Discussion

Tumefactive MS lesions are defined as solitary demyelinating plaques greater than 2 cm.⁵ Lesions are difficult to distinguish between primary or metastatic given similarity of imaging features.⁵ Imaging features suggestive of Tumefactive MS include incomplete ring enhancement, absence of mass effect and absence of cortical involvement.^{6 7} Kim describes that CT hypoattenuation of magnetic resonance enhancing lesions was found to be highly specific for distinguishing Tumefactive MS lesions from CNS cancer pathology.⁶ It has been shown that SPECT using I-IMP is useful for diagnosing CNS malignancy.³ This is because there would be increased uptake in comparison to the MS lesions - implying increased metabolic activity.³ However this study has its limitations in diagnosis. In a few isolated cases I-IMP was found in greater quantities in MS tumor-like lesions.³

The imaging studies for this patient established a concern for metastasis, infection or primary malignancy. Extensive cancer workup was completed as previously discussed. Since all tumor markers were negative a baseline PET scan was considered however, was not done secondary to insurance denial. Due to the asymptomatic presentation of her disease, a primary differential diagnosis of brain metastasis and anticoagulation therapy for PE, a CSF analysis was not considered until much later. We were able to use surveillance MRI and CSF analysis to see some resolution of these lesions and confirm the diagnosis. Brain biopsy was never warranted but in unique symptomatic cases it may have been.⁶

The cornerstone of diagnosing MS is the demonstration of lesions in both time and space - termed the McDonald Criteria.⁸ The revised criteria allow a diagnosis of MS, “possible MS” or “not MS”.⁸ This is what made the diagnosis of our patient difficult, as no clinical symptoms or attacks were evident. It was demonstrated that over the course of three months the lesions seen on MRI evolved. From the size of 1.5 cm, 1.0 cm and 1.0 cm they became 1.3 cm, <1.0 cm and <1.0 cm respectively (Figure 2, Figure 4). This was likely the effects of steroids that the patient was on due to her vasogenic oedema. Here an evolution in time and space is demonstrated which excluded brain metastasis and infection. This brings into discussion the diagnostic value of surveillance MRI, which in our case was helpful and appropriate as the patient did not have clinical symptoms.

Conclusion

The diagnosis of Tumefactive MS can be extremely difficult and time consuming. As seen in our case, it can mimic other conditions. Our patient was able to be diagnosed with MRI surveillance and CSF analysis. The definitive diagnostic test for MS is a brain biopsy but this is not preferred due to the invasiveness of the procedure. With the advent of newer diagnostic tests such as SPECT, MR Spectroscopy, surveillance MRI and CSF analysis, diagnosis can be attained and treated presumptively.

CASE

A 79 year old lady presented to the accident and emergency department with severe abdominal pain. On admission she was hypotensive and hypothermic. Blood tests demonstrated raised inflammatory markers and white count, but were otherwise unremarkable. A CT scan revealed no abnormalities. She was treated with intravenous fluids and empirical antibiotics.

She had multiple co-morbidities, including ischaemic heart disease, hypertension and chronic kidney disease.

Figure 1 – Upper Oesophagus

Figure 2 – Distal Oesophagus

Figure 3 - Gastro-eosophageal Junction

Figure 4 – Stomach (in retroflexion)

Figure 5 - Duodenum

Three days into her admission she had a single episode of hematemesis and a gastroscopy was arranged. Endoscopic features were as per figures 1- 5. Histology taken at the time showed necrotic tissue with evidence of candidiasis. Her treatment was optimised with a two-week course of fluconazole with the dose adjusted for her renal function and parenteral nutrition, with good clinical response. She was discharged after a two week hospital admission. A repeat gastroscopy 10 weeks later showed complete resolution of endoscopic features with no evidence of perforation or stricture formation.

DISCUSSION

The images seen at endoscopy demonstrate a region of oesophageal ulceration progressing to a diffuse, circumferential, black discoloration of the distal esophageal mucosa, with an abrupt transition to normal mucosa at the gastro-esophageal junction (Figs. 1-3). These endoscopic features, in the absence of a history of ingestion of caustic substances, are diagnostic of Acute Oesophageal Necrosis (AON), also known as ‘Black Oesophagus’. Whilst histology confirming necrosis is not necessary to make the diagnosis, it is confirmatory.

AON was first described in 1990 by Goldberg et al, since which over one hundred cases have been reported in the literature¹. Population studies have suggested the incidence of this condition to be between 0.08% and 0.2%, although interestingly one post-mortem series of 1000 patients failed to reveal any cases^2-4. There is a male preponderance, with an incidence four times greater than that for women and a peak incidence during the sixth decade of life^{5, 6.}

The aetiology of this condition is not entirely clear; however case reports to date suggest that this is almost exclusively observed in those who are systemically unwell, usually in the context of multi-organ dysfunction^5-7. It has been postulated that necrosis most commonly occurs as a consequence of hypo-perfusion caused by a low flow state in those with underlying vascular disease. This is likely to account for the predilection for the distal third of the esophagus, which is relatively less vascular⁵. Individual cases have occurred in association with bacterial, viral and fungal infections, whilst malnutrition, malignancy and immune-compromise appear to be important factors^{3, 5, 6}.

The most common indication for the gastroscopy that makes the diagnosis of AON is hematemesis and melena, accounting for over 75% of cases⁶. It is therefore likely that AON is significantly under reported as endoscopy is often precluded in those who are clinically unstable. Further it is not clear whether hematemesis is a universal symptom of this condition; it is conceivable that AON may go undiagnosed in those in whom this is not a feature.

Whilst AON has no specific treatment, its presence is indicative of significant systemic compromise and predicts a poor prognosis. This diagnosis should alert physicians that close monitoring and aggressive treatment is required to optimise patient outcomes. There is no clear role for the use of anti-acid therapy, however this is commonly used in management due to patient symptoms, which usually includes hematemesis. Similarly, candidiasis may occur in conjunction with AON, whilst it is not thought to be causative, treatment is considered prudent given the poor prognosis associated with this condition.

For those that recover from their acute systemic insult the prognosis appears to be good. The long-term sequale of this condition includes oesophageal stenosis due to structuring. Evaluation with a repeat gastroscopy if therefore indicated if dysphagia develops.

CONCLUSION

The clinical course of AEN is variable, with an associated mortality of 32%⁵. The severity of the underlying clinical condition appears to be the most important factor in determining prognosis. There is no specific treatment for AON. The current body of experience suggests aggressive management of abnormal physiology optimises outcomes^{5, 6}. Antibiotics, antifungals and nutritional support should be considered on an individual basis.

INTRODUCTION

Although it is well appreciated that pancreatitis is frequently secondary to biliary tract disease and alcohol abuse, it can also be caused by drugs, trauma and viral infections, or even be associated with metabolic and connective tissue disorders.¹ Knowledge of the true incidence of drug-induced acute pancreatitis is dependent on the clinician’s ability to exclude other possible causes, and by promptly reporting the occurrence. Based on individual case reports and case control studies of drug-induced acute pancreatitis, the estimated overall incidence ranges from between 0.1 and 2% of pancreatitis cases.^2,3 In particular, drug-induced acute pancreatitis is of mild severity and usually resolves without significant complications.⁴

Attempts have been made to categorize the risk of drugs causing acute pancreatitis. A previous classification system described by Mallory and Kern Jr. categorized drugs associated with acute pancreatitis as definite, probable, or possible.⁵ Trivedi et al. proposed a newer classification system for commonly used medications associated with drug-induced pancreatitis. Class I drugs are those medications with at least 20 reported cases of acute pancreatitis and at least one case with a positive rechallenge. Drugs with fewer than 20 but more than 10 reported cases of acute pancreatitis, with or without a positive rechallenge, are designated into Class II. While those medications with 10 or less reported cases, or unpublished reports in pharmaceutical or FDA files, are grouped into Class III.⁶

Acute pancreatitis as a result of either doxorubicin or cyclophosphamide, or a combination of both, or fluorouracil or epirubicin is a rare occurrence and has seldom been reported in the literature. Even the drug package labels registered with the FDA do not indicate the possible occurrence of pancreatitis. In this case report, we present a rare occurrence of drug-induced acute pancreatitis after the completion of the first cycle of the chemotherapy protocol involving cyclophosphamide and doxorubicin in a patient with stage 3 breast cancer, with recurrences of acute pancreatitis after re-challenging with cyclophosphamide and a derivative of doxorubicin, given individually on two separate occasions.

CASE PRESENTATION

A 58 year-old female presented to the emergency room with a one day history of severe, diffuse, deep-seated abdominal pain that radiated to her back, associated with nausea and vomiting, and was unrelieved despite the intake of NSAIDs. There was no reported fever, chills, diarrhea, dysuria, or antecedent trauma. Her medical history is notable for well-controlled hypertension, hyperlipidemia and hypothyroidism for which she takes amlodipine, atorvastatin and levothyroxine. She was recently diagnosed with left-sided breast cancer, Stage III, two months prior to admission and underwent a left modified radical mastectomy. Three days prior to the hospital visit, she was given her first cycle of chemotherapy with Doxorubicin 60 mg/m² and Cyclophosphamide 600 mg/m² along with Pegfilgrastim 6 mg and Fosaprepitant 150 mg. She is a former cigarette smoker, drinks alcohol infrequently, and denies illicit drug use. Her family history is unremarkable.

Physical examination revealed stable vital signs without a fever (36.6^◦C). She had non-icteric sclerae and a dry oral mucosa. Chest exam revealed a well-healed left mastectomy scar and an infusaport located on the right anterior chest wall. Her breath sounds were clear bilaterally. Her heart sounds were normal. Her abdominal exam was significant for mild tenderness to palpation in the epigastric area without palpable masses, organomegaly or ascites. There was no evident ecchymosis observed. The extremities were warm to touch with intact and symmetrical pulses, and without bipedal edema.

Initial work-up revealed an elevated leukocyte count of 42,000 with 80% neutrophils and 17% band forms. Basic metabolic panel was normal except for mild hyponatremia of 129 mEq/L. Serum amylase and lipase were markedly elevated at 2802 units/L and >2000 units/L, respectively. Liver function panel was normal (Alk phos 63 U/L [ref range 30-115 U/L], GGT 21 U/L [ref range 3-40 U/L], total bilirubin 0.90 mg/dL [ref range 0-1.5 mg/dL]). The coagulation profile was within normal range. Imaging of the abdomen with a CAT scan with intravenous and oral contrast showed haziness in the pancreatic fat plane suggestive of pancreatic inflammation, with no gallstones, focal abscesses, hepatic masses, or biliary ductal dilatation (Figure 1). Right upper quadrant ultrasound was essentially normal (Figure 2).

Figure 1. Coronal view of CT scan of abdomen and pelvis with IV and oral contrast showing haziness in the peripancreatic fat plane.

Figure 2. Sonogram of the right upper quadrant of the abdomen showing gallbladder devoid of gallstones and non-dilated common bile duct.

She was admitted to the medicine unit with the assessment of acute pancreatitis likely secondary to doxorubicin and cyclophosphamide. Intravenous fluid hydration with normal saline was initiated. She was kept NPO (nothing per os) and was started on empiric Imipenem and IV Esomeprazole. Her abdominal pain was controlled with intravenous morphine and her nausea with Ondansetron as needed. The serial basic chemistry panel was monitored and electrolyte deficits were replaced accordingly. Further work-up was performed to identify other possible etiologies of pancreatitis. The lipid panel was within normal limits (cholesterol 169 mg/dL [0-200 mg/dL], HDL 74 mg/dL, LDL 71 mg/dL and triglycerides 54 mg/dL [0-150 mg/dL]). The serum calcium levels remained within the normal range throughout her hospital stay. An abdominal sonogram demonstrated absence of gallstones or dilatation of the common bile duct, with a normal appearing liver parenchyma and pancreas. During her stay in the medicine unit, the patient’s abdominal pain improved and she was gradually started on an oral diet, which she tolerated well. Her serum electrolytes remained stable, while her serial CBC revealed progressively decreasing trends in leukocytes, hemoglobin, hematocrit, and platelet count, findings which were attributed to her prior chemotherapy. Repeat serum amylase and lipase both trended downward. The patient was discharged with follow up in the Oncology clinic. A month later, she was started on another chemotherapy regimen that consisted of weekly administration of Paclitaxel 80 mg/m² which, over the next two months, the patient completed without any complications. Then, after explaining the risks of recurrent pancreatitis, the patient consented to have a trial of cyclophosphamide 500 mg/m² along with fluorouracil 500 mg/m². Five days after receiving the chemotherapy, the patient developed acute pancreatitis which was attributed to cyclophosphamide. She again made a full recovery at that time. Three weeks later, her chemotherapy regimen was again changed, to epirubicin 90 mg/m² and fluorouracil. Four days after receiving this regimen, she again, for the third time, had a recurrence of acute pancreatitis. At this time, a repeat abdominal sonogram revealed a 4mm echogenic focus adherent to the anterior gallbladder wall with a comet tail sign, suggestive of cholesterol crystals lodged within Rokitansky-Aschoff sinuses of the gallbladder wall. There were no visible gallstones. A subsequent MRI of the abdomen with contrast revealed a small rounded hypointensity in the dependent portion of the gallbladder wall that was suggestive of a gallstone, however, there was no biliary obstruction, choledocholithiasis or an obstructing pancreatic mass. At this point, chemotherapy was stopped and anastrozole along with radiation therapy was initiated. The patient continues to be followed regularly and has had no recurrence of pancreatitis since her last episode.

DISCUSSION

The case presented described the development of acute pancreatitis in a patient with breast cancer three days after receiving the chemotherapy regimen consisting of cyclophosphamide and doxorubicin. After re-challenging the patient with cyclophosphamide, and again a few weeks later with a derivative of doxorubicin, epirubicin, acute pancreatitis recurred on each occasion. Despite the presence of cholelithiasis detected on the abdominal MRI, the temporal presentation of acute pancreatitis after chemotherapy exposure is highly suggestive of the role these chemotherapeutic agents played in triggering these three acute attacks. Acute pancreatitis was diagnosed based on the clinical suspicion and symptoms suggestive of the acute pancreatitis and was supported by the marked elevation in serum amylase and lipase, as well as, the radiologic evidence of pancreatic inflammation, both of which are markers of acute pancreatitis.

Chemotherapy-induced acute pancreatitis involving cyclophosphamide and doxorubicin either alone or in combination, is quite rare that even the drug labels registered with the FDA do not indicate acute pancreatitis as one of the possible complications. This scenario highlights the importance of drug surveillance and prompt reporting in order to maintain a credible drug safety database.

Though the drug latency, which is the interval between the initial exposure to the drug and the development of acute pancreatitis, differs variably, the present case is considered to have an intermediate latency (1-30 days). Other drugs may have short (< 24 hours) or long (>30 days) latency periods. Examples of drugs with short latency are acetaminophen, codeine, erythromycin and propofol. Intermediate latency drugs include L-asparaginase, pentamidine and stibugluconate. Drugs with long latency are estrogen, tamoxifen, valproate and dideoxyinosine.⁷

Based on the revised classification of Badalov et al, the combination of cyclophosphamide and doxorubicin is classified as Class IV drugs, which have the weakest association with acute pancreatitis due to limited information and the lack of adequate detailed case reports. Fluorouracil, which has been known to cause a gastrointestinal ulcer, is also categorized as a Class IV drug, while epirubicin, which is derived from doxorubicin, has not been classified, as it has not been reported before to cause acute pancreatitis. In implicating drugs in the etiology of acute pancreatitis, two conditions must be considered to weigh the strength of the association between the causality and the disease process, namely: a positive rechallenge test resulting in the recurrence of pancreatitis and a similar latency period between the drug exposure and development of the disease.⁷

The combination of drugs rather than a single agent was implicated for drug-induced pancreatitis in a previous case report that described the development of acute pancreatitis shortly after the second cycle of the chemotherapy regimen composed of cyclophosphamide, doxorubicin, and vincristine in a patient with mediastinal immunoblastic lymphoma. The pancreatitis episode resolved over 48 hours without complications.⁸

Another case was described in a patient with breast cancer developing acute pancreatitis four days after the third cycle of chemotherapy, which involved docetaxel and carboplatin.⁹

Toprak et al. reported the occurrence of acute pancreatitis in a patient with multiple myeloma after the initial treatment with the triple regimen chemotherapy protocol consisting of vincristine, doxorubicin, and dexamethasone. In this case report, symptoms suggestive of acute pancreatitis started to manifest on the first day of the treatment, with resolution following discontinuation of the drugs.¹⁰

Other antineoplastic agents for breast cancer associated with drug-induced pancreatitis are alemtuzumab, trastuzumab and tamoxifen. Extended use of these medications may cause chronic pancreatitis as a result of their causing repeated clinical or subclinical episodes of acute pancreatitis.⁶ Most cases of drug-induced pancreatitis follow a mild clinical course.⁷

In a retrospective study involving 1613 patients diagnosed with acute pancreatitis in a gastroenterology center, the incidence of drug-induced pancreatitis had been reported in 1.4% of patients treated for acute pancreatitis. It has been observed that a higher incidence of drug-induced acute pancreatitis occurs in elderly or pediatric patients, and in those patients with inflammatory bowel disease or AIDS.¹¹

The pathophysiology behind drug-induced pancreatic injury remains unclear. Potential mechanisms underlying such pancreatic injury might be related to drug hepatotoxicity which can be secondary to intrinsic toxicity of the drugs affecting the tissue, or due to an idiosyncratic reaction. In the vast majority of the cases, an idiosyncratic reaction could be the main pathway for tissue injury through a hypersensitivity reaction or production of toxic intermediate metabolites. Idiosyncratic reactions have a longer latency period of months to years before the onset of pancreatitis while the onset of hypersensitivity reactions is earlier (i.e. 1-6 weeks).⁷

CONCLUSION

Due to a variable latent period between the initial drug exposure and the onset of clinical symptoms, drug-induced pancreatitis must remain as a differential diagnosis in patients receiving chemotherapy regimens and presenting with the constellation of symptoms typical of acute pancreatitis. Due to the unclear pathogenesis of chemotherapy-induced pancreatitis, post-marketing surveillance and adverse drug reporting are paramount in elucidating the effect these drugs have on the pancreas.

Introduction

Binge Eating Disorder (BED) was first defined by Stunkard in 1959¹; he identified peculiar food intake features characterized by a loss of control in a subgroup of obese patients. Various efforts have been made, ever since, to provide a non-sociological approach to individuals with such a behaviour disorder, which has long been considered a variant of Bulimia Nervosa.

Unlike patients affected by Bulimia Nervosa, patients with BED appear to be overweight and mainly obese. Thus, the treatment aims not only at reducing BED and its related psychopathology, but also at assessing the weight gain experienced by these patients to prevent a further worsening of physical health.

Walsh & Devlin² evaluated the use of medication in the treatment of Bulimia Nervosa and BED, underlining the efficacy of antidepressant medication in the treatment of Bulimia Nervosa. The antidepressant efficacy led to consider its use in BED more accurately.

Williamson, Martin & Stewart³ stated that pharmacotherapy was not an effective treatment for Anorexia Nervosa. However, it did prove to be successful in Bulimia Nervosa and BED, although subjects affected with eating disorders apparently respond better to psychotherapy approaches.

Systematic investigations have been conducted on the aetiology of BED. Biological and genetic factors, neurotransmitters and hormones have been involved in the onset of binge eating and play an important role in the regulation of hunger and mood.^{4, 5} However, a definitive aetiological theory has not been developed and tested.³

BED is characterized by a relevant psychological component that in many cases is under-evaluated. Patients with BED have difficulty in interpreting the visceral sensations of hunger and satiety; they take large amounts of food even during regular meals and, moreover, their food contains more fat than protein.^{6, 7}

In fact, Axis I and II disorders (DSM IV-TR) share common features with binge eating.⁸ Axis I psychiatric disorders (including depression, anxiety, body dysmorphic disorder, or chemical addiction) characterize many BED patients, and research has evidenced the presence of panic, loss of control, impulsivity, compulsive behavior, obsessive thoughts about food and social phobia.⁹ Axis II personality disorders (especially borderline personality disorder) are frequently related to patients suffering from eating disorder and comorbidity with Avoidant Personality Disorder and Obsessive-Compulsive Disorder was observed.¹⁰

BED is not associated with a restrained eating control, but probably with an increase of uncontrolled eating and emotional eating.^{11, 12}

Pharmacological agents, compared to placebo, have been used in the treatment of BED. Appolinario, Bacaltuchuk, Sichieri et al¹³ evaluated the efficacy of Sibutramine to reduce the frequency of binge eating, while McElroy, Arnold, Shapira et al¹⁴ focused on Topiramate and evidenced a greater reduction in binge eating frequency but with side effects such as paraesthesia.

Other studies showed the efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs) in the treatment of obesity associated with BED^{15, 16, 17, 18} showing that SSRIs and Tricyclic Antidepressants (TCAs) reduced the frequency of BED compared to placebo.¹⁹ To determine which patients are most likely to benefit from medications, and how to sequence the various therapeutic interventions available better, are questions still open to debate.

Moreover, results in many cases appear to be divergent. Ciao, Latner and Durso²⁰ underlined the influences of other factors that may influence treatment efficacy. They observed that many obese individuals who might benefit from weight loss treatment nevertheless do not plan or desire to seek treatment and perceive multiple barriers to treatments.

Pharmacotherapy may enhance weight loss,¹⁹ although other results suggest that pharmacotherapy may be associated with a reduction in binge frequency in obese patients with BED, but it does not lead necessarily to weight reduction.²¹ These medical treatments seem to be effective in reducing binge frequency over the short-term, and the subsequent discontinuation of the medication seems to be associated with a relapse of binge eating. Thus further studies of the role of pharmacotherapy in the treatment of BED need to be carried on.²²

According to Williamson, Martin and Stewart³ the additive effects of psychotherapy, e.g. Cognitive Behavioural Therapy (CBT), and pharmacotherapy have to be investigated. At present it seems that adding pharmacotherapy to psychotherapy does not help to reduce binge frequency compared to psychotherapy alone.

The efficacy of CBT has been substantiated by scientific literature^{23, 24, 25, 26} and Vaidya²⁷ stating that CBT helps patients reduce eating disorder habits by making them aware of the cause of their self-sabotage, while affecting weight indirectly.

Psychotherapy treatment over a one-year period deals with binge symptoms and aims at reducing the possibility of relapse by gathering different techniques for the maintenance of long-term results through the use of specific individual intervention protocols. The main target of the intervention is to facilitate the management of no-control food intake episodes and of impulsivity through the alteration of behaviour, and of cognitive and emotional factors related to eating disorders.

Thus, the main objective of this research was to verify the possible differences between those subjects with BED who underwent psychotherapy combined with pharmacotherapy and those who underwent psychotherapy only. In particular, it aimed at verifying possible differences between the various therapeutic strategies on eating behaviour (restrained eating, uncontrolled eating and emotional eating) and the behavioural and psychopathological features (psychopathic deviate, depression and hypomania).

The main hypothesis was to determine if patients who underwent CBT and pharmacotherapy with bio-equivalent doses of the SSRI Paroxetine or SNRI Venlafaxine obtained a considerable benefit from the pharmacotherapy on impulse regulation, on eating behavior and on personality features compared to those who underwent CBT alone.

The second hypothesis was to verify if Paroxetine and Venlafaxine treatments were equally effective on impulse regulation, eating behavior and on personality characteristics.

Methodology

Participants

A group of 30 subjects with BED were selected. All these subjects applied for support to the Inter-Service-Psychology Clinic for Eating Disorders and they were assisted by a Cognitive Behavioural Therapist. They were all of Italian nationality, aged 22 to 52, with a Body Mass Index (BMI) range of 26 to 35. All participants belonged to a middle class socio-cultural level. They were informed of the objectives of the research and signed a consent form. Those subjects who were diagnosed with binge eating less than two years ago, those aged over 65, or those who were suffering from other debilitating or chronic diseases were preliminarily excluded from this research.

Measures and procedure

Participants were recruited according to the nature of the assessments. More specifically, assessments had to address the effect of psychotherapy and pharmacotherapy in subjects with BED on their impulse regulation, their eating behavior (restrained eating, uncontrolled eating and emotional eating), and their personality features (Psychopathic Deviate, Depression and Hypomania). The 30 subjects selected were randomly assigned to three different treatments. Ten subjects had only CBT, ten subjects underwent psychotherapy with Paroxetine, and ten subjects underwent psychotherapy with Venlafaxine.

Each participant answered questionnaires during the assessment phase and in the post-training phase (after one year of psychotherapy). More specifically:

Binge Eating Scale (BES)²⁸ is a 16-item questionnaire which assesses the presence of binge eating behaviour indicative of an eating disorder. The score ranges from 0 to 46 (non-binging <17; moderate binging = 18-26; severe binging = 27 and higher), which in this research had an adequate internal consistency (a = 0.84).

Eating Disorder Inventory-2 (EDI-2)²⁹ aims at quantifying some psychological and behavioural features. It consists of 64 questions grouped into 11 scales. For each item, the participants are asked to answer by using the following frequency adverbs: "always", "usually", "often", "sometimes", "rarely", and "never". The rating is measured with a score between 0 and 3: the maximum score of 3 corresponds to the intensity of the symptom ("always" or "never" depending on whether the direction of the item is positive or negative), score 2 corresponds to a degree intensity immediately below ("usually" or "rarely"), score 1 to an even lower level of intensity ("often" or "sometimes"), while a score of 0 is assigned to the three "asymptomatic" answers. So, those items with a positive direction are assigned the following scores: always = 3, usually = 2, often = 1, sometimes = 0, rarely = 0, never = 0; items with a negative direction are evaluated in the opposite way: never = 3, rarely = 2, occasionally = 1, and often, usually, always = 0. The sub-scale scores are calculated by simply adding all the scores of items of each specific sub-scale.

This research availed the Impulse Regulation Scale with an adequate internal consistency (a = 0.82). This scale shows the ability to regulate impulsive behaviour, especially binge behaviour.

Three Factor Eating Questionnaire (TFEQ)³⁰ is a self-report questionnaire consisting of 51 items.The questionnaire refers to daily dietary practice and measures three different aspects of eating behaviour: (1) restrained eating (conscious restriction of food intake in order to control body weight or to promote weight loss – cut-off: ≤11; a = 0.79); (2) uncontrolled eating (tendency to eat more than usual due to a loss of control over intake accompanied by subjective feelings of hunger – cut-off: ≤8; a = 0.81): (3) emotional eating (inability to resist emotional cues – cut-off: ≤7; a = 0.83).

Minnesota Multiphasic Personality Inventory-2 (MMPI-2)³¹ consisting of 567 items with dichotomy answers (true/false) is most commonly used by mental health professionals to assess and diagnose mental illness. The MMPI is based on ten clinical scales that are used to indicate different psychotic conditions. In this research the scoring of the three following scales were taken into consideration: (1) Psychopathic Deviate Scale (Pd) (50 items) which measures social deviation, lack of acceptance of authority and amorality. This scale can be thought of as a measure of disobedience. High scorers tend to be more rebellious, while low scorers are more likely to accept authority. An adequate internal consistency was obtained in this research (a = 0.83); (2) Depression Scale (D) (57 items). The highest scores may indicate depression, while moderate scores tend to reveal a general dissatisfaction with one’s own life. A sound internal consistency was obtained through this research (a = 0.81); (3) Hypomania Scale (H), with 46 items, identifies such characteristics of hypomania as elevated mood, accelerated speech, locomotive activity, irritability, flight of ideas, and short periods of depression. In this research the internal consistency was a = 0.79.

Results

The Statistical Package for Social Science (SPSS 10.1) was implemented to verify the hypothesis. The limited number of subjects enabled analysis of data through non-parametric statistics. In order to verify statistical differences between simple comparisons on paired data the Mann-Whitney (U) test³² was applied. In order to verify statistical differences within phases (pre- Vspost-training), Wilcoxon Signed Ranks Tests³³ were calculated separately on paired data.

Table 1 synthesizes the means and standard deviations of eating behaviour and of impulse regulation obtained by the three groups: CBT alone; psychotherapy with Paroxetine (CBT+P); and psychotherapy with Venlafaxine (CBT+V) in pre- and post-treatments.

Table 1 – Minimum and maximum scores, Means and Standard Deviations of eating behaviour and of impulse regulation obtained by three differential groups.

By comparing the total scoring in BES during the pre-treatments phase, no statistical differences between groups were noticed. Subjects who only underwent CBT had the same result than those who had addition of Paroxetine (CBT+P) [U = 64; Z = 0.35; p = 0.75] and Venlafaxine (CBT+V) [U = 59; Z = 0.62; p = 0.55]. There were no initial statistical differences between the two groups that received pharmacotherapy [U = 50; Z = 0.1; p = 0.99].

In the post-treatment phases, the presence of binge eating behaviour appeared to be the same in all groups. Subjects belonging to the CBT group obtained the same results as those belonging to the CBT+P [U = 58; Z = 0.68; p = 0.5] and the CBT+V groups [U = 47; Z = 1.36; p = 0.19]. No statistical differences between medication use were noticed [U = 41; Z = 0.69; p = 0.53].

All groups in post-treatment phases seem to equally benefit from the treatment. Comparing scores obtained by participants in the pre- and post-treatments, statistically significant differences were found in subjects undergoing CBT [Z=3.38, p < 0.001] and those with the addition of Paroxetine [Z = 2.848; p < 0.004] and Venlafaxine [Z = 2.859, p < 0.004].

For this research, Impulse Regulation Scale scores were taken into consideration. In the pre-treatment phase relative to each group, all groups showed the same difficulties to regulate impulsive behaviour. The CBT group showed the same impulse regulation as those belonging to the CBT+P [U = 68; Z = 0.12; p = 0.93] and CBT+V group [U = 64; Z = 0.33; p = 0.75]. No initial statistical differences between pharmacotherapy groups were found [U = 45; Z = 0.39; p = 0.74].

In post-treatment, no statistical differences between groups were observed. The CBT group achieved the same results as the CBT+P [U = 60; Z = 0.56; p = 0.58] and CBT+V group [U = 64; Z = 0.32; p = 0.75]. No statistical differences between the use of Paroxetine and Venlafaxine were found either [U = 39; Z = 0.84; p = 0.44].

All groups seemed to benefit from the treatments. In fact, comparing the scores obtained by participants in the pre- and post-treatments, statistically significant differences were observed in subjects who underwent CBT [Z = 3.38, p < 0.001] as well as in subjects supported by Paroxetine [Z = 2.84; p < 0.005] and Venlafaxine [Z = 2.97, p < 0.003].

Table 2 synthesizes the means and standard deviations of different features of eating behavior (restrained eating,uncontrolled eating andemotional eating)showed by the three groups (CBT, CBT+P, and CBT+V) in pre- and post-treatment.

Table 2 – Minimum and maximum scores, Means and Standard Deviations of different aspects of eating behavior (restrained eating, uncontrolled eating and emotional eating) obtained by three differential groups

In eating behaviour as well, all groups in pre-treatment phases appeared to be equivalent. The CBT group had the same mean result in restrained eating than those subjects who also underwent pharmacotherapy [CBT+P: U = 65; Z = 0.33; p = 0.74; and CBT+ V: U = 53; Z = 1.03; p = 0.55]. In the pre-training no statistical differences between groups with pharmacotherapy were noticed [U = 42; Z = 0.59; p = 0.58].

By analyzing the groups in pre-treatment phases no statistical differences in uncontrolled eating behaviour and emotional eating behaviour were found. In pre-treatment phase, the CBT subjects had the same statistical mean in uncontrolled eating [U = 48; Z = 1.33; p = 0.21] and in emotional eating [U = 48; Z = 1.32; p = 0.21] as those who took Paroxetine. No statistical differences were found when comparing CBT subjects with those that were taking Venlafaxine [uncontrolled eating: U = 48; Z = 1.33; p = 0.21; emotional eating: U = 48; Z = 1.32; p = 0.21]. In the pre-training phase there were no statistical differences between groups with pharmacotherapy [uncontrolled eating: U = 46; Z = 1.44; p = 0.17; emotional eating: U = 51; Z = 1.12; p = 0.28] were found.

All groups showed indistinctively less difficulty on restrained eating habits. In fact, by comparing post-training scores, the participants of CBT obtained the same results as those treated with Paroxetine [U = 61; Z = 0.56; p = 0.62] and Venlafaxine [U = 58; Z = 0.75; p = 0.51]. Therefore CBT alone appeared to be less effective on reducing uncontrolled eating than those with the addition of Paroxetine [U = 30; Z = 2.4; p < 0.02] and Venlafaxine [U = 26; Z = 2.6; p < 0.009]. Participants who underwent only CBT presented with less difficulties on emotional eating control than those with Paroxetine [U = 31; Z = 2.31; p < 0.02], but they achieved the same post-treatment score as those supported by Venlafaxine [U = 52; Z = 1.08; p = 0.31].

Comparing post-treatment outcomes, the effectiveness of Paroxetine and Venlafaxine appeared to be the same on restrained eating behaviour [U = 34; Z = 1.2; p = 0.25], on a better controlled eating behaviour [U = 45; Z = 0.39; p = 0.69] and on a higher emotional eating control behavior [U = 33; Z = 1.29; p = 0.2].

Comparing pre- and post-treatment results helped to observe a significant improvement in all groups. Participants who followed only CBT showed less difficulty to restrained eating behaviour [Z = 2.6; p < 0.009] in post-treatment. The same results were observed in those supported by Venlafaxine [Z = 2.12; p < 0.03], while no statistical differences were detected in a post-treatment phase in those groups supported by Paroxetine [Z = 1.89; p = 0.06].

Moreover it was possible to observe a considerable decrease in uncontrolled eating behaviour in all groups [CBT: Z = 3.49; p < 0.0001; CBT+P: Z = 2.84; p < 0.005; CBT+V: Z = 2.88; p < 0.004]. The same results were observed in the way emotional eating was handled. All groups benefited from treatments [CBT: Z = 3.27; p < 0.001; CBT+P: Z = 2.46; p < 0.01; CBT+V: Z = 2.87; p < 0.004].

Table 3 synthesizes means and standard deviations of Psychopathic Deviate (Pd), Depression (D) and Hypomania scales (H) obtained by the three groups (CBT, CBT+P, and CBT+V) in pre- and post-treatments.

Table 3 – Minimum and maximum scores, Means and Standard Deviations of different aspects of Psychopathic Deviate obtained by three differential groups

As evidence of the homogeneity of the groups, the comparisons revealed no statistically significant differences in the pre-treatment phase. The CBT group subjects and those who received Paroxetine [Pd: U = 58; Z = 0.67; p = 0.51; D: U = 55; Z = 0.85; p = 0.39; H: U = 63; Z = 0.41; p = 0.71] showed similar scores. Likewise, the CBT group subjects and those treated with Venlafaxine [Pd: U = 53; Z = 0.99; p = 0.34; D: U = 58; Z = 0.71; p = 0.51; H: U = 65; Z = 0.26; p = 0.79] showed similar scores. The two groups treated subsequently with pharmacological support showed similar initial scores as well [Pd: U = 44; Z = 0.46; p = 0.68; D: U = 50; Z = 0.1; p = 0.99; H: U = 44; Z = 0.45; p = 0.68].

Comparing the results obtained in the post-treatment phase instead, those participants exposed to CBT alone showed a greater reduction of Pd compared to those who had taken Paroxetine [U = 23; Z = 2.76; p < 0.005] and Venlafaxine [U = 23; Z = 2.77; p < 0.005], whereas no differences were found comparing the scores obtained post-treatment in both groups of subjects with pharmacological treatments [U = 41; Z = 0.65; p = 0.53].

In post-treatment, the CBT group participants showed similar scores when compared to those taking Paroxetine [D: U = 54; Z = 0.91; p= 0.37; H: U = 41; Z = 1.67; p = 0.09] and Venlafaxine [D: U = 44; Z = 1.49; p = 0.14; H: U = 49; Z = 1.2; p = 0.23]. There have been no further significant differences in scores obtained post-treatment by the two pharmacotherapy groups [D: U = 39; Z= 0.84; p = 0.44; H: U = 0.47; Z = 0.23; p = 0.85].

All participants seem to have benefited from the proposed treatment. The CBT group had a significant reduction of Pd [Z = 3.3; p < 0.001], D [Z = 3.37; p < 0.001] and H [Z = 3.19; p < 0.001].

A similar result was found by comparing the pre- and post-treatment scores of the subjects supported by Paroxetine [Pd: Z = 2.7; p < 0.007; D: Z = 2.82; p < 0.005; H: Z = 2.82; p < 0.005].

Even in the group treated with Venlafaxine, a significant reduction of Pd [Z=2.87; p< 0.004], D [Z = 2.84; p < 0.004] and H [Z = 2.81; p < 0.005] was confirmed.

Discussion

The use of pharmacological therapy for overweight patients with BED has been less thoroughly studied. SSRIs (Citalopram, Sertraline, Fluoxetine, and Fluvoxamine) have mainly been used as the active compound in the pharmacological trials of patients with BED in order to improve mood symptoms and weight loss.³⁴ Likewise, in many cases, promising results have been obtained with Venlafaxine in BED.³⁵

Most of the research has focused on specific aspects of binge eating disorder, such as reduction in binge frequency and weight reduction. In general the results are associated with higher discontinuation rates.³⁶

In this research, we did not only focus on the binge eating behaviour and impulse regulation in patients with BED. The main objective of this research was to analyze some aspects of eating behaviour (restrained eating, uncontrolled eating and emotional eating) and, more specifically, different psychotic conditions (psychopathic deviate, depression and hypomania).

The first hypothesis of this research was to verify differences between patients with binge eating disorder that followed CBT either with or without a pharmacotherapy support. The results confirmed that CBT and pharmacotherapy are equally effective in the treatment of BED and equally modified patients’ impulse regulation. Paroxetine and Venlafaxine medications did not enhance the control of binge eating or guarantee management of impulse regulation better than CBT alone.

This research also aimed at evaluating the efficacy of CBT with or without pharmacotherapy on some factors related to eating behaviour, such as the tendency to consciously monitor and reduce the caloric intake (restriction), the tendency to lose control on food intake (uncontrolled eating) and the conscious perception of the sensation of craving for food (emotional eating). The results suggest that CBT offers the same results regarding the reduction of caloric intake (restriction) as pharmacological treatment. It is less efficient in reducing the lack of control in food intake (uncontrolled eating), although it helps to reduce the sensation of craving for food (emotional eating) compared to pharmacotherapy.

In this research the effects of standardized treatments of CBT with or without the use of pharmacotherapy with bio-equivalent doses of Paroxetine and Venlafaxine were analyzed on psychopathic deviation, depression, and hypomania. The results confirmed that CBT showed a greater reduction of psychopathic deviation compared to those groups who underwent pharmacotherapy. Moreover, pharmacotherapy led to a higher reduction of depression and hypomania than CBT alone.

The second hypothesis was to verify if the SSRI Paroxetine and SNRI Venlafaxine were equally effective on impulse regulation, eating behaviour and personality features. The analysis showed that Paroxetine and Venlafaxine were equally effective on binge eating control and impulse regulation, but some differences in reducing dysfunctional eating behavior were found. Venlafaxine, compared to Paroxetine, seems to offer a greater improvement in emotional eating and restriction eating behavior. In fact CBT could be efficient to assess the tendency to reduce caloric intake (restriction) and to reduce the sensation of craving for food (emotional eating) more than Paroxetine alone. In order to reduce the tendency to lose control on food intake (uncontrolled eating) it could be helpful to administer Paroxetine or Venlafaxine.

Limitations

While the clinical groups were equivalent in all the parameters taken into consideration in the pre-treatment phase, the absence of a control group (no treatment) significantly reduced the possibility to accurately verify the conclusion. Due to ethical reasons we were not allowed to select a group of patients without any specific treatment. In order to correct this weakness in the research, it might be helpful to extend the sample and analyze the changes over a longer period of time.

It is relevant to analyze appropriately these aspects through controlled trials in order to test the efficacy and long-term outcome of psychotherapy, pharmacotherapy, and psychotherapy in combination with pharmacotherapy for treating BED.

Conclusion

In conclusion, patients with eating disorders usually suffer from other psychiatric disorders besides their eating disorder. Many results also confirm substantial comorbidity among obesity, BED, mood and anxiety disorders and metabolic syndrome in weight loss seeking populations.³⁷

In such cases, it is important to understand the characteristics of the additional psychiatric disorders and the impact these ones have throughout the treatment.

As underlined by American Dietetic Association (ADA) Reports,³⁸ understanding the complexities of eating disorders, such as influencing factors, comorbid illness, medical and psychological complications, is critical in the effectiveness of the treatment of eating disorders.

Eating disorders are complex medical illnesses since they have psychological, behavioural, and physiological components. Previous researchers underlined the importance to investigate gender differences in binge eating and associated behavioural correlates³⁹ and, in order to prevent eating disorders, it is important to carry out individual treatment even on personality traits if the individual disorders have already occurred.⁴⁰ Of course, a multidisciplinary approach involving a collaborative team of psychological, nutritional, and medical specialists as underlined in this research must be pursued in order to obtain important and at least short-term results.⁴¹

The results of this research confirm the need to analyze BED from an integrative perspective and to suggest treatments based on an interdisciplinary approach. The psychological (CBT) and pharmacological (Venlafaxine and Paroxetine) therapies were both efficient in different ways on the reduction of all the negative variables related to eating disorder. However any treatment could be inadequate in the absence of an accurate diagnosis that takes into consideration biological, genetic, psychological and nutritional components.

The assessment phase still plays an important role in determining which treatment is best for each patient. Accuracy in the medical examination when dealing with medical issues, as well as during the assessment examination and the psychological functioning evaluation is recommended.

Introduction

Brain injury is a major cause of mortality and morbidity all over the world and in Europe there is an estimated incidence of 235 brain injury inpatients per 100,000 population ¹. Over the years, the medical care of brain injuries has developed with a resultant fall in mortality. However, with this fall in death rates the proportions of people with complications, especially the neuro-behavioural effects of brain injury, has risen ². Of the complications, psychiatric disorders have a significant impact on the patient’s quality of life and rehabilitation prognosis³ and so are an important consideration from both a care delivery and public health perspective. This paper therefore aims to analyse the prevalence of psychiatric disorders following brain injury and highlight the practical and personal implications of these through an illustrative case series.

Depression Following Brain Injury

Jorge et al in 2004⁴ conducted a prospective case controlled study on a sample of 91 patients with traumatic brain injury (TBI). Patients with penetrating head injury, spinal cord injury and severe deficits of comprehension was excluded and 27 patients without brain injury but with other trauma was included as controls. The sample was analysed at 3, 6 and 12 months with Present State Examination (PSE), structured clinical interview for DSM1V, and analysed with Mann Whitney and chi squared tests. The results showed that 33% of the TBI group had major depression compared to 22 % in the control group. Neuropsychological testing also demonstrated that depressed patients had a greater degree of impaired cognitive function. An earlier study with a larger sample was conducted by Kreutzer in 2001⁵, studying 722 TBI patients (average time post injury for evaluation 2.5 years). Data was collected via survey, using the Neurobehavioral Functioning Inventory to identify depression; the response was studied by trained neuropsychologists and compared with DSM-IV Criterion for depression. A significant proportion (42%) of survey respondents met the DSM-IV criterion for depression. Fatigue, low concentration and frustration were most commonly reported symptoms. A similar study done by Seel et al in 2003⁶, where 666 TBI outpatients from 17 centres was reviewed using DSM-IV Criterion, showed rates of major depression to be 27%.

Mania Following Brain Injury

Jorge in 1993⁷ reviewed 66 patients with brain injury at 3, 6 and 12 month intervals to evaluate the prevalence of mania. The inclusion criteria was age above 18 years and absence of delirium, no previous history of mood disorder and absence of grave injuries to other areas of the body. Using the Present State Examination to gather data, 9% of the sample had symptoms in correlation with the DSM III criteria for mania.

Van Reekum in 1996⁸ recruited 18 TBI patients attached to a rehabilitation unit for a study to evaluate mental illness in this population. 44% of patients had severe TBI while 56% had mild/moderate TBI; the average duration since TBI was 4.9 years. 27% met the DSM II criteria for bipolar affective disorder and 61% met criteria for depressive illness. The rate of anxiety disorder was 38% but psychosis was not reported.

Psychosis & Other Mental Illness Following Brain Injury

Fann et al in 2004⁹ conducted a large prospective cohort study involving 1939 randomly selected TBI patients 1 year pre injury and 3 years post injury to study rates of psychiatric illness including psychosis. The sample was divided into the moderate/severe TBI and mild TBI compared to matched controls. The presence of psychiatric illness was detected by utilisation of mental health services by subjects, usage of psychotropic medication and presence of a psychiatric diagnosis in the records. Psychotic disorders were seen in 49% of the moderate to severe TBI patient group and for the mild TBI group psychosis was seen in 34% of the sample. This is significantly greater than the rate seen in the control group. However the lack of definitive diagnostic criteria and confounding factors such as social circumstances and other physical health issues which may have strong associations with mental illness were not accounted for.

Another observational prospective study done by Rao et al in 2009¹⁰ looked into prevalence rates of aggression in the 3 months following brain injury. Overt Aggression Scale was used by trained examiners in the assessment of aggression in a sample of 107 TBI patients. Comorbidities were analysed using General Medical Health Rating scale; psychosocial functioning was analysed by Social Functioning Exam and the Social Ties Checklist. Results showed the prevalence of aggression in the sample to be 28.4% and this subgroup was also associated with new-onset major depression. Only 63% of the already small sample completed the study and the drop out group was unaccounted for; this may negatively impact the results.

Keenan et al in 2008¹¹ studied prevalence of attention-deficit hyperactivity disorder(ADHD) in 2782 post TBI children and demonstrated chance of a diagnosis of ADHD two folds higher amongst children with a head injury before age 2. Jellinger in 2004¹² studied links between brain injury and dementia, and found that although cognitive deficit was associated with brain injury, there was no established link between development of dementia and brain injury. Oquendo et al in 2004¹³ studied 325 depressed patients to analyse the link with mild TBI and suicidal behaviour; 44% of the sample had mild TBI and suicidal behaviour was more common in this subgroup. Suicide Intent Scale and the Lethality Rating Scale was used to measure suicidal behaviour. However, exclusion of moderate to severe TBI and inclusion of only inpatients in this study would affect any generalisability of the results.

Case series: Psychiatric Disorders Following Brain Injury

Case 1- Patient A: Epilepsy, interictal psychosis and organic personality disorder following head injury

Patient A is a 37 year old female under mental health services with a diagnosis of organic personality disorder and interictal psychosis. She suffered from epilepsy from the age of 9 but coped well at school and went on to work successfully as a hairdresser. However, in 1998 at the age of 22 she was admitted to ITU with status epilepticus as a result of encephalitis of unknown cause, and remained severely unwell for several months. She recovered but was left with residual tonic clonic and complex partial seizures.

Since this episode, marked changes in her personality were noted. She developed mood swings with recurrent episodes of low mood, and expressed paranoid beliefs about people in the street talking about her. These beliefs resulted in her being agitated and physically aggressive, resulting in harm to both herself and others. She has required numerous admissions to acute wards and rehabilitation units because of her paranoid and suspicious behaviour and aggressive outbursts that her family were not able to manage in the community. She required restraint under Section 3 of the Mental Health Act in 2010, believing that care staff were poisoning her. Psychotic symptoms are most marked around seizures, with her displaying self harming behaviour such as cutting off hair or painting face with nail polish. She frequently accuses staff and family of acting against her in these periods and her behaviour is very difficult to manage.

Her case has been challenging to manage successfully in the community by family and community teams, and she has needed several short and long term stays in acute wards and residential units. Her care has been coordinated jointly between neurological and psychiatric services. She currently lives with her parents and has carers to support her. Her epilepsy is yet to be successfully controlled; antipsychotics can lower the seizure threshold and so a delicate balance between these and her antiepileptic medication is warranted. There is an on-going concern that further mental health problems may develop in light of this.

Case 2- Patient B: Schizophrenia following head injury

Patient B is a 43 year old female with a diagnosis of schizophrenia, learning difficulties and epilepsy. She suffers from epilepsy in the form of absence and tonic-clonic seizures from the age of 7 months, when there is high suspicion that she sustained a head injury whilst in the care of extended family. Patient B has difficulties with numeracy and literacy, identified through psychological assessment, and an IQ of around 70. She has required three admissions under Section 2 of the MHA due to her paranoid delusions and poor self care. Patient B frequently reports feeling monitored by cameras, suspicions that her food has been poisoned and that her personal belongings are being tampered with. She has attempted to take her own life due to feeling unable to cope with these delusions, laying in the road to be run over by a bus.

She is currently managed well in the community on oral risperidone for her psychosis and sodium valproate for her epilepsy; she resides in supported accommodation and has required stints in long term residential and rehabilitation beds due to her mental health problems and learning difficulties.

Case 3- Patient C:Depression and Personality disorder after head injury

Patient C first came in to contact with psychiatric services in 2007 and was diagnosed with depression and organic personality disorder. At the age of 16 this gentleman was knocked off his bicycle and sustained a severe head injury, from which he was left in a coma for over three weeks, but recovered well enough to go home. In 1994 he started having blackouts, was investigated extensively by neurology, and diagnosed with non-epileptic attack disorder. As part of these investigations, Patient C underwent an MRI which demonstrated significant brain damage including traumatic damage to the frontal lobes. This was likely due to his accident at age 16. From his first assessment by psychiatric services, he eluded to thoughts and behaviours that were of serious concern to his team. He reported feeling emotionally detached from his family, gaining little pleasure from life, getting in to fights frequently and allegedly having stabbed someone in an altercation several years ago. He described to practitioners only getting excitement out of reading and watching programmes about serial killers, and occasionally became sexually aroused by this. He had made extensive written plans on how he would capture, torture and kill the couple he believed were responsible for his accident at 16. He also struggles with auditory command hallucinations telling him to harm himself and others. He frequently self harms, often using a Stanley knife to cut his arms and legs. Patient C has been jointly managed by adult psychiatry and neuropsychiatry on an outpatient basis. His risks of aggression and violence have been carefully managed through regular assessment and involvement of forensic services.

Conclusion:

The literature search indicates that the prevalence of psychiatric disorders in patients with brain injury is much higher compared to general population. The significance of the results are however greatly affected by response bias, the impact of patients’ cognitive impairment on their study participation, observer biases and the small study population sizes; however, we believe that these short-fallings should be seen as a trigger to stimulate more comprehensive and wide-scale research in to this field. The methodologies used by authors described in the literature review demonstrate the wide variance in the tools used to assess psychiatric illness in patients following TBI; we therefore argue that universal case definitions need to be agreed on and implemented to standardise studies and reduce bias. The economic impacts and impacts on quality of life have often been neglected by researchers and warrant formal assessment. From a service delivery perspective, rehabilitation programs need to identify patients with signs of psychiatric illness post TBI earlier and involve psychiatric service in the development of integrated care plans to improve the total outcome and quality of life of the patient. The impact on the patient’s family and carers also need to be explored further to provide an evidence base for more effective and holistic interventions.

A 26 year old male was brought to Emergency department with history of altered sensorium of 1 day duration. He had a 2 week history of fever prior to admission. On examination, meningeal signs were present. Fundus examination showed evidence of papilloedema and a round pale yellow spot near the optic disc (Figure 1). CT scan of head did not reveal any abnormality.

Mantoux test and HIV ELISA were negative. CSF analysis showed:  

• Glucose – 40mg/dl;  Protein: 2gm/l;   
• Cell Count: 1200cells/µl;
• Cell Type: 80% lymphocytes;
• CSF VDRL- negative;
• CSF Grams stain, India ink staining and Ziehl Neelsen staining were unremarkable.

What is the Fundus finding?

1. Roth Spot
2. Cotton Wool Spot
3. Choroidal tubercle
4. A-V malformation

Discussion:

Correct answer: 3) Choroidal Tubercle.

Intraocular tuberculosis is a rare event and occurs in 1% of all diagnosed cases of tuberculosis.¹ It occurs by haematogenous spread of mycobacterial organism. Choroidal tuberculosis is the most common initial manifestation of intraocular tuberculosis. They may be seen in 1.4% to 60% of patients with different forms of tuberculosis and are highly specific for tuberculosis. ^{2, 3}

Choroidal tubercles may be unilateral or bilateral and appear as polymorphic yellowish lesions with discrete borders. They are of 2 types, solitary tubercle or granuloma (seen in chronic tuberculosis) and choroidal miliary tubercles (seen in acute miliary tuberculosis). Their size varies from 0.4 to 5 mm and may be associated with retinal vasculitis, panuveitis, choroiditis and neuroretinitis.

When they involve macula they present with visual loss and any delay in appropriate treatment results in irreversible visual loss. Peripherally situated tubercles are asymptomatic.  Definitive diagnosis can be daunting due to difficulty in getting ocular samples for histological evaluation, however when available reveal features of granulomatous inflammation. Fundus angiography exhibits hypofluorescence in early stages and hyperfluorescence in later stages.

On treatment they heal by varying degrees of scar formation and marginal pigmentation.⁴ Untreated tubercles grow into large tumour like mass called tuberculoma.

Roth spots are retinal haemorrhages with a pale centre and are associated with bacterial endocarditis. Cotton wool spots appear as fluffy white patches on the retina and are associated with diabetes. A-V malformations are developmental vascular anomalies and appear as marked arterial and venous dilation associated with a tortuous pattern of vessels. They may have an associated bruit or chemosis of the eye.

The presence of ocular tuberculosis may be subtle. A high index of suspicion is required for its diagnosis. Delay in treatment or misdiagnosis may lead to irreversible visual loss. 

Evidence has consistently shown that patients with mental illness have greater physical health morbidity and mortality compared to the general population.¹ Many factors have been implicated and include a generally unhealthy lifestyle, side effects of medication, and inadequate physical healthcare.^{2, 3} Higher rates of suicide and accidents are other known risks. Psychiatric patients are more likely to smoke, have less inclination to exercise, and are prone to poor dietary habits and obesity, the latter through general inertia, the result of the adverse effects of neuroleptic medication, or increased alcohol use. Psychotropic medication is associated with impaired glucose tolerance and diabetes, metabolic syndrome, dyslipidemia, cardiovascular complications, extrapyramidal side effects and sexual dysfunction.  A broad range of clinician and organisational factors prevent access to adequate physical healthcare that in turn compounds the above problems.

Scale of physical morbidity and mortality in mental illness

Patients suffering from depression are twice as likely to develop type 2 diabetes mellitus, and the prevalence of stroke and myocardial infarction is three- and five-fold respectively higher than people without depression.⁴ A mortality rate ratio (MRR) of 2 to 3 in patients with schizophrenia or bipolar disorder is a general finding.⁵ Schizophrenia is associated with higher rates of diabetes mellitus (side effects of medication partly to blame), osteoporosis (lifestyle risk factors play a role), obesity, and cardiovascular problems^{. 2, 6, 7, 8} It has been estimated that life expectancy is reduced by at least ten years. ^{9, 10} People with learning disabilities, particularly those with concurrent epilepsy, dementia and polypharmacy, are at greater risk of developing added complications.¹¹ Eating disorders are associated with a high mortality because of physical disorders caused by anorexia/bulimia nervosa affecting other organ systems.¹² Mental illness in general is associated with an increased risk of hepatitis, human immunodeficiency virus (HIV), tuberculosis, and poor dental health. ^{9, 10}

Causes of raised physical health morbidity and mortality in psychiatric patients

Explanations for the higher morbidity and mortality in mental illness include cardiovascular and respiratory problems in addition to the increased suicide risk. Aetiological factors include adverse effects of medication (weight gain, diabetes, and dyslipidemia), lifestyle (smoking and the cost of smoking, poor diet and nutrition, lack of exercise, and obesity) and inability to access physical healthcare. Obesity, smoking and physical inactivity contribute to hypertension. Poor physical healthcare outcomes in mental illness are related to a combination of factors generally considered under the headings of patient/illness, psychiatrist/physician, and service provider/system issues.

De Hert and colleagues ^{9, 10} have outlined the factors that account for the raised physical health problems.  For instance the patient/illness factors comprised difficulty in understanding health care advice combined with the motivation required to adopt new changes in lifestyle, poor compliance with treatment, cognitive deficits, reduced pain sensitivity (induced by antipsychotic medication), poor communication and deficient social skills (seen in many cases of schizophrenia, for example) which all accounted for the shortened life-span of patients with severe mental illness (SMI). 

An additional patient/illness factor is that psychiatric symptoms may render patients less inclined to discuss physical problems. Some doctors are uncomfortable dealing with psychiatric patients because the latter may be cognitively compromised which may impair or impede a doctor’s clinical assessment. The stigma of mental illness, often the result of disparaging media coverage and negative stereotypes surrounding psychiatric patients, are other hurdles that prevent people from seeking treatment. Furthermore, psychiatric patients are less likely to see a primary care physician and therefore to receive other interventions such as screening for cancer.

Psychiatrist-related factors are characterised by an overemphasis on mental health to the exclusion of physical health, infrequent screening rates for metabolic abnormalities, omission of medical examination of patients because physical complaints frequently are part of the psychiatric presentation, poor communication with the patient and the primary care teams, a lack of awareness and perhaps adherence to treatment guidelines, insufficient medical knowledge, and erroneous, sometimes misguided beliefs about patients’ capability to change their lifestyle.^{9, 10} Even when risk factors are documented in the patient's clinical file, very little is done by way of further investigations or prevention.

Factors common to the psychiatrist and other physicians include a tendency to dismiss or interpret physical symptoms as psychosomatic, lack of good quality care, unequipped teams, insufficient assessment, and difficulties providing consistent monitoring and continuity of care. Other physician-related factors relate to problems coordinating psychiatric and medical care.^{9, 10}

Service-provision factors included a lack of clarity and consensus as to where the responsibility of physical health lies.^{9, 10} Should general practitioners (GPs) supervise the majority of patients who do not suffer from severe, enduring mental illness? Should patients with acute alcohol withdrawal symptoms be managed at home by the GP, treated in a general hospital, or admitted to a psychiatric unit? The fragmentation of medical and mental health care systems, lack of integration of services (poor or absent liaison links) and insufficient funds to resource the mental health service, limit the ability of most psychiatrists to focus beyond their own speciality. 

Service and system changes are prevalent in industrialised countries because reforms in mental health have led to reduced inpatient resources leading to shorter and infrequent hospital admissions with less time available to focus or investigate physical health problems. In the United Kingdom (UK) there is intense emphasis on community care and talking therapies, yet the management of physical health issues by community mental health teams may be poor because of inadequate training and learning. 

Recommendations to improve physical health care in psychiatric patients

Health care professionals need to be more aware of these findings in order to improve medical screening and treatment of psychiatric patients. Currently there is no evidence this is happening, with increasing concerns regarding inequalities between those with and without mental illnesses.¹³

We propose the following recommendations to promote integration between mental and physical health care:

1.    A greater effort to increase awareness of the problem among primary care and mental health care providers. The Royal College of Psychiatrists has launched a campaign called Fair Deal to highlight the importance of physical health of people with mental illness.¹ Patients still feel stigmatised and therefore psychiatrists need to boost their efforts to reduce this discrimination. The excess mortality associated with this discrimination needs to be recognised as a human rights issue.¹³

2.    Primary care providers need to change the culture of undertreating physical health in mental health patients. The National Institute for Health and Clinical Excellence (NICE) guidelines for schizophrenia and bipolar disorder highlight the importance of monitoring antipsychotics and mood stabilizers.¹⁴ The Royal College of Psychiatrists should lead by implementing the NICE guidelines for mental and behavioural conditions. 

3.    Education and training of doctors who pursue a career in psychiatry needs to be improved with mandatory trainee placements in acute medicine or neurology, regular personal development plan (PDP) courses, and training to update knowledge of recognising physical illness and the performance of basic medical tasks. The Royal College of Psychiatrists should develop a diploma in clinical psychiatry for GPs and clinicians with a specialist interest in psychiatry. The curriculum needs to be widened to include electrocardiogram (ECG) interpretation, basic endocrinology, and neurological investigations (magnetic resonance imaging and so forth). This would allow psychiatrists to develop better liaison with their fellow professionals and share responsibility with them, which undoubtedly would encourage good medical practice. 

4.    The Royal College Scoping Group’s report¹⁵ sets key standards for the physical healthcare of patients in a range of psychiatric services. It outlines the responsibilities of psychiatrists monitoring the physical health of patients, such as problems associated with adverse effects of medication. The report recommends that psychiatrists are trained and kept up to date in relevant physical health matters. These recommendationsneed to be followed.

5.    Mental health professionals should encourage patients to monitor simple measures such as weight, dietary plans, and exercise programs, with the involvement of the voluntary sector (MIND, Mental Health Foundation) where possible. Patients and carers need to be educated about the health risks associated with unhealthy lifestyles: for example, smoking and alcohol misuse may interfere with the metabolism of neuroleptic medications. Smoking cessation clinics and alcohol treatment programmes may help. Advice from dieticians about patients' nutritional requirements to offset changes in metabolism caused by neuroleptics is important. 

6.    Because of the large-scale reduction of inpatient psychiatric beds and service redesign the majority of psychiatric care provision now exists in the community. Therefore community mental health teams and psychiatric outpatient clinics need to be appropriately designed and equipped to enable proper assessment of physical health monitoring. Annual health checks from the GP would benefit patients who require long-term monitoring in the community. Screening for deleterious effects of medication for example, hypothyroidism and renal dysfunction caused by lithium, at regular intervals would be appropriate.¹⁶ It should also be made clear to psychiatrists that they should resist working in clinical settings that compromise patient care and inhibit good medical practice.

7.   Financial initiatives such as Commissioning for Quality and Innovation (CQUIN)¹⁷ may be used by commissioners to improve physical health monitoring.  As part of this process, primary care commissioners could mutually agree with mental health providers to fulfil measured targets related to such monitoring.

8.    In order to better understand the interplay between psychiatric conditions and medical complications contributing to the high physical morbidity and mortality, further studies are essential. To cite one example, we now know that psychotropic medications contribute to many physical problems (abnormal ECGs, weight gain, changes in plasma glucose) and lead to higher morbidity rates. The 'newer' generation of antidepressants and neuroleptics have not lived up to expectations and have as many untoward effects as the older drugs. Developments of newer drugs with different mechanisms of action are required, though this will take time. 

9.    The discrimination faced by people with mental illness and learning disabilities, with the accompanying excess mortality, represents a human rights issue¹³ that requires legislative changes. The Disability Right’s Commission¹⁸ has already recommended appropriate physical health care screening, for example, annual physical health checks. The government’s health inequality agenda should incorporate these conditions into its indicators of disadvantage and include mental illnesses and learning disability in the framework.

Conclusion

Traditionally the field of psychiatry involves a holistic approach in the management of patients. Unfortunately, over the decades psychiatry appears to have lost its way and therefore it is important to re-establish a more comprehensive system of treating mental illness that encompasses regular physical health monitoring. Physical morbidity and mortality in patients with mental illness is on the rise and is associated with a complex interplay of factors outlined above. The overall health care of psychiatric patients can be improved through the changes in education and training of clinicians, close liaison between primary and secondary care, implementation of recommendations by NICE and the Royal College of Psychiatrists, improved research through better funding, public health education of patients and carers, and legislative changes.

Isaac Asimov famously said: ‘The only constant is change.’ (Cited in Hartung, 2004).

So why is it so difficult for most of us to understand, manage, or embrace change?

Coping with change can be challenging for many and, depending on the change and what the impact or outcome of the change means to the individual, will depend upon how well they embrace and accept it. Should a person be fearful of change then it is natural that they will attempt to resist it which in turn can cause high levels of stress and anxiety.

Understanding how we typically react to change also helps us to cope better and manage change. The Kubler-Ross (2009) Model of Change is perhaps one of the best known and most applied models within clinical environments (her original work being around the five stages of grief) which is now also applied to businesses and organisations when looking at changes in the work place such as loss or change of job.

The five stages she refers to are:

1. Denial
2. Anger
3. Bargaining
4. Depression
5. Acceptance

A common example used to explain this model is to understand how we would typically respond to an unexpected change such as a dead car battery.

The dead car battery

Just imagine it is a cold winter day and you are dashing to get to work already running late…

You jump into the car, place the key in the ignition and turn it on.

Nothing happens, the battery is dead.

Applying the Kubler Ross Model to this situation, this is how a person may typically react:

1. Denial - This cannot be happening! Try again. And again! Check the other things in the car are working such as the lights and radio. Try again but still nothing.
2. Anger - Arrrrgh you stupid car!!! I’m sick of this car!! Why is this happening today of all days!! Slamming a hand against the steering wheel.
3. Bargaining - (realising that  it really isn’t going to start and that you're going to be late for work)..., Oh please car, if you will just start one more time I promise I'll buy you a brand new battery and keep you clean and tidy. Please just start this one time.
4. Depression - Oh no! What am I going to do? I'm going to be late for work. I give up. I don't really care any more. What's the use?
5. Acceptance - Right I need to do something. It is not going to start. I need to call the breakdown service and ring into work.

The above example is a simple example yet I’m sure most of us have experienced it or something similar quite often. If you apply this to a situation where the stakes are far higher such as a sudden loss or change of a job, bereavement, house, relationship etc which may impact upon so many things including stability of finances, family, health and other forms of security, then you may be able to see the harsh effect this could have on an individual during this time.

Often individuals add to their stress by expecting themselves to be able to cope with such events. It is important to understand it is not about strength or weakness but about human nature to react by demonstrating the signs of loss and grief. Organisations, managers and individuals need to be understanding and supportive when situations like this happen.

Another way of understanding and coping with change is to consider what goes on in the mind of the individual at the time of the change and what it ‘means’ to them. Some people see risk and uncertainty as exciting and embrace change (depending on the change), whereas others can be fearful of any change, even those perceived to be minor changes, as for them any change is seen as a risk and takes them out of their comfort zone.

The comfort zone

Your comfort zone is where you are fully able, competent and comfortable. The job that you can do with your eyes shut or routines of life where you know exactly what you are doing. You may feel slightly challenged now and then, but there’s nothing you cannot easily handle. 

When invited to step outside their comfort zone – or if they’re pushed outside of it - many people react with resistance. This is because of the human fear of failure which, when you look into it more deeply, comes from a desire to be accepted, liked and even loved. When most people ‘fail’ they feel embarrassed, ashamed, silly or stupid because they feel they can’t or couldn’t do whatever it was they tried.

So it’s understandable if at work, or any area of life where there is change, people react with resistance. Change is the unknown, and if you don’t know whether you can do something – especially if you have a ‘Be Perfect’ driver – you could have fears over whether you can do it, can be a success or even cope. Everyday changes such as new computers or telephone systems, new staff, new jobs, new routines and procedures, new management, merging of departments, sections or whole companies or, on a personal level, exams, weddings, divorce, births, deaths, moving house and so on, are all high on the list of stressors due to change.  

How big is your zone?

Are you resistant to change? If you are, you’re causing yourself stress. Imagine what size a child’s comfort zone would be compared to an adult’s. Children do not have inhibitions and fears; it’s only as we grow older that we learn to feel fear, that we learn what embarrassment is and how to feel silly or stupid – that is, we learn to have an ego. This restricts our ability to have the freedom to learn, grow and be open to change, as we are nervous about asking questions for fear of looking silly, or trying new things for fear of failure, and we avoid doing anything that may cause us to feel embarrassed.

By being more fluid and open to change, accepting any fear and dealing with it effectively, you would not only grow your confidence and self-esteem, but you will be free to develop your life with more happiness and less stress. 

By looking at change differently (for example, recognising that change can also be a good thing; focusing on the possible positives from a situation rather than being quick to look at the negatives from a point of fear and therefore resistance) stress can be greatly reduced.

Choose to flow with change rather than resist; choose to step out of your comfort zone and grow the size of your comfort zone daily. Aim to have a comfort zone the size of a child’s where nothing can faze or worry you, and you will notice a huge difference to the amount of stress you have in your life.

‘The greatest discovery of my generation is that a human being can change their life by altering their attitude of mind.’ William James (cited in Maxwell, 2007).

Remember – the only failure is not trying again. If we fail at something at least we know what NOT to do next time!

Identifying your zones and being rational

Following are three simple exercises you can complete to help you to gain a rational perspective on understanding how you cope with change and also being solution focused when embracing change.

The zones of change help us to understand the different levels of comfort or ‘risk’ and where changes may sit in terms of their percieved meanings to the individual.

Zones of change

Exercise 1

Think back to a significant change in your life or work (something from the past).

• What were your perceived risks at the time?

…………………………………………………………………………………

…………………………………………………………………………………

• What did you lose?

…………………………………………………………………………………

…………………………………………………………………………………

• What did you gain?

…………………………………………………………………………………

…………………………………………………………………………………

This exercise demonstrates that our ‘perceived risks’ at the time of a change were often far different than the reality of how the change occurred. It is also common for an individual to notice that their ‘gains’ can be larger than their ‘losses’ (time can play a factor in this too, often a change can seem a disaster at the time but over time a person can look back and be glad it happened in comparison to how their life is now.)

Exercise 2

Think of a change that you are currently undergoing.

• What aspects of the change are in your ‘comfort zone’?

…………………………………………………………………………………

…………………………………………………………………………………

• What aspects are in your ‘risk zone’?

…………………………………………………………………………………

…………………………………………………………………………………

• What aspects are in your ‘high risk zone’?

…………………………………………………………………………………

…………………………………………………………………………………

• What do you need to make the ‘high risk’ into ‘risk’ and the ‘risk’ into ‘comfort’?

…………………………………………………………………………………

…………………………………………………………………………………

This exercise is excellent for considering a current change and how it may affect a person.

Actually listing in categories the level of ‘risk,’ or even drawing the zones on a piece of paper and writing in each change in the place on the zone where the person believes it sits, will give a rational perspective.

Once all the ‘risks’ are highlighted then that is the time to minimize ‘risk’ and find solutions for the individual to cope or manage that change. This is good for action planning and allowing a person to take control to embrace a change rather than being reactive once the change has occurred.

Exercise 3

Think of a life or work change which is going to occur in the future.

Blockers

• What I’d be sorry to lose.

…………………………………………………………………………………

…………………………………………………………………………………

• My fears and concerns.

…………………………………………………………………………………

…………………………………………………………………………………

Drivers

• Benefits of the change.

…………………………………………………………………………………

…………………………………………………………………………………

• What I’d be glad to leave behind.

…………………………………………………………………………………

…………………………………………………………………………………

Answering these questions assists a person to determine how much resistance they may feel/have towards a change. Listing potential blockers will identify fears and concerns of the change as well as the levels of risk and loss. Listing drivers will encourage the individual to consider the benefits of the change, the gains, and that change can also be a good thing.

Typically, whichever list is the longest or has the most meaning/impact will be the strongest for that person. If this is the blockers they will resist the change and cause themselves pressure and stress. Therefore addressing the zones of change and looking for ways to reduce risk would be a good strategy in action planning to manage the change well. Should the drivers be the strongest for the person then they are likely to embrace the change more readily although they may still need to address their thoughts and rationale for any blockers listed.

Change tips:

• Embrace change, as if you don’t accept it someone will push you into it.
• Take every opportunity to grow your comfort zone.
• Have the attitude that there is no failure and only learning and development – when we ‘fail’ we know what NOT to do next time.
• The worst rarely happens, so why waste energy focusing on it and enforcing irrational fears?
• Change CAN be a good thing.
• There is always a solution, it may take time for you to see it, but if you look, you will find it.

Introduction:

Foreign body ingestion is a common occurrence, especially in children, alcoholics, mentally handicapped and edentulous people wearing dentures. However, majority of the individuals pass these objects without any complications.¹ Most foreign bodies pass readily into the stomach and travel the remainder of the gastrointestinal tract without difficulty; nevertheless, the experience is traumatic for the patient, the parents, and the physician, who must await the removal or the ultimate passage of the foreign body.² The alimentary canal is remarkably resistant to perforation: 80% of ingested objects pass through the gastrointestinal tract without complications. ³   About 20% of ingested foreign bodies fail to pass through the entire gastrointestinal tract.⁴ Any foreign body that remains in the tract may cause obstruction, perforation or hemorrhage, and fistula formation. Less than 1% result in perforations from the mouth to the anus  and those are mostly caused by sharp objects and erosions. ^{5, 18}  Of these sharp objects, chicken bones and fish bones account for half of the reported perforations. The most common sites of perforation are the ileo-ceacal junction and sigmoid colon.³

Materials and Methods

This  study, “Gastrointestinal tract perforations due to foreign  bodies; a review of 21 casesover a  ten year period”  was carried out in the Department of General Surgery at the Sher-i-Kashmir  Institute of Medical Sciences Srinagar (SKIMS), a tertiary care hospital in North India, from  January 2002 to December 2011. A total of 21 consecutive patients who underwent surgery for an ingested foreign body perforation of the GI tract over a period of ten years were retrospectively reviewed. Computer database and extensive case note search of patient’s personal data including age, sex, residence, presenting complaints with special stress on clinical examination findings was done. The type and nature of the foreign objects, mode of entry into the gastrointestinal tract, preoperative diagnosis, perforation site, and treatment received were recorded. The complications arising due to perforation of GIT because of the foreign body ingestion and complications arising due to specific treatment received were noted. Important findings on various laboratory tests, including a complete blood count, erythrocyte sedimentation rate, [pre-op/post-op/follow up], blood cultures, and serum chemistry, chest and abdominal X-rays were penned down. Special efforts were made to identify the predisposing factors for ingestion of foreign bodies including edentulous patients with dentures, psychosis, extremes of age and hurried eating habits. Clinical, laboratory and radiological findings, treatment modalities, operative findings and  therapeutic outcomes were summarized. Data collected as such was described as mean and percentage.

I/V Antibiotics ( Ceftriaxone + Metronidazole ) were given in the emergency room and changed to specific therapy as per the culture sensitivity postoperatively.

Results

The average follow up duration was 13 months (range 7 – 19 months). There were 14 male(66.66%)  and 7 female (33.33%) patients ranging in age from 7 years to 82 years with a median age of 65 yrs at the time of diagnosis . The most frequently ingested objects were dietary foreign body (n = 17). Four patients had  ingested objects like toothpicks (n =2) and metallic staples (n=2) {as shown in figure 1}. Among the dietary foreign bodies fish bone was found in 7(33.3%) and chicken bone in 10(47%) {as shown in figure 2} . All the patients described their ingestion as accidental and involuntary. A definitive preoperative history of foreign body ingestion was obtained in 4(19.04%) patients and an additional 9(42.8%) patients admitted ingestion of foreign body in the post operative period. Of these 13 patients the average duration between ingestion of foreign body and presentation was 9.3 days. Remaining 8 (38.09%) patients did not recall any history of foreign body ingestion; dietary or otherwise. In terms of impaction and perforation of ingested foreign body, ileum was the commonest site with 14(66.66%) patients showing perforation near the distal portions of the ileum followed by sigmoid colon in 5(23.8%).  Jejunal perforation was seen in 2(9.5%) patients.

Fig 1: X ray abdomen AP view showing ingested metallic pin

Fig 2: Intra operative picture showing perforation of small gut due to chicken bone

All our patients presented with acute abdomen and were admitted first in emergency department. Since majority of patients did not give any specific history of foreign body ingestion, they were managed as cases of acute abdomen with urgency and level of care varying according to the condition of patients. Eight patients presented with free air in the peritoneum and air under the right side of diaphragm. The most common preoperative diagnoses were acute abdomen of uncertain origin: 12 (57.14%); acute diverticulitis:5 (23.8%) and acute appendicitis: 4 (19.04%).

Table 1: Showing demographic profile, site of perforation, etiology, presentation and management.

All the patients underwent an emergency celiotomy and confirmation of foreign body induced perforation was possible in all the 21 patients .Patients with a suspected appendicitis were explored via classical grid iron incision and rest via midline incision. Varying degrees of abdominal contamination was present in all the patients. Out of the 21 patients 11(52.38%) underwent removal of foreign body and primary repair of their perforations after minimal debridement. Intestinal resection with stoma formation (resection of the perforated ileum and ileum stoma) was done in 10 (47.6%) of the 21 patients as shown in Table 1. Take down of stoma was done at a later date. Three (14.28%) patients developed incisional superficial surgical site infection which responded to local treatment. Two (9.5%) patients died in the postoperative period due to sepsis. One patient (Patient no. 3 in table 1) who was a diabetic on Insulin, Chronic obstructive pulmonary disease and Hypertension died on 3^rd postoperative day in surgical Intensive care unit due to severe sepsis. Another patient, (Patient no. 12 in table 1 ) an elderly female with no co-morbid illness developed severe sepsis due to Pseudomonas aeruginosa, died on 4^th postoperative day. She was managed at a peripheral primary care center for first 3 days for her vague abdominal pain with minimal signs. All the other patients had an uneventful recovery and were discharged home between 6-14^th postoperative day. 

Discussion:                      

Foreign bodies such as dentures, fish bones, chicken bones, toothpicks and cocktail sticks have been known to cause bowel perforation⁶. Perforation commonly occurs at the point of acute angulation and narrowing. ^{7, 8}  The risk of perforation is related to the length and the sharpness of the object.⁹   The length of the foreign body is also a risk factor for obstruction, particularly in children under 2 years of age because they have considerable difficulty in passing objects longer than 5 cm through the duodenal loop into the jejunum. In infants, foreign bodies 2 or 3 cm in length may also become impacted in the duodenum.¹⁰   The most common sites of perforation are the ileo-ceacal junction and sigmoid colon. Other potential sites are the duodeno-jejunal flexure, appendix, colonic flexure, diverticulae and the anal sphincter.³ Colonic diverticulitis or previously unsuspected colon carcinoma have been reported as secondary findings in cases of sigmoid perforation caused by chicken bones.^11,12 Even colovesical or colorectal fistulas have been reported as being caused by ingested chicken bones. ^13,14 .In our study ileum was the most common site with 14 patients showing perforation near the distal portions of the ileum followed by sigmoid colon. Jejunal perforation was seen in 2 patients.

The predisposing factors for ingestion and subsequent impaction are dentures causing defective tactile sensation of the palate, sensory defects due to cerebro-vascular accident, previous gastric surgery facilitating the passage of foreign bodies, achlorhydria where the foreign body passes unaltered from the stomach, previous bowel surgery causing stenosis and adhesions and diverticula predisposing to impaction.³ Overeating, rapid eating, or a voracious appetite may be contributing factors for ingesting chicken bones. The mean time from ingestion to perforation is 10.4 days.¹⁵ In cases when objects fail to pass the tract in 3 to 4 weeks, reactive fibrinous exudates due to the foreign body may cause adherence to the mucosa, and objects may migrate outside the intestinal lumen to unusual locations such as the hip joint, bladder, liver, and peritoneal cavity.¹⁶ The length of time between ingestion and presentation may vary from hours to months and in unusual cases to years, as in the case reported by Yamamoto of an 18 cm chopstick removed from the duodenum of a 71-year-old man, 60 years after ingestion.¹⁷ In our study the average duration between ingestion of foreign body and presentation was 9.3 days.

In a proportion of cases, definitive preoperative history of foreign body ingestion is uncertain.¹⁸ Small bowel perforations are rarely diagnosed preoperatively because clinical symptoms are usually non-specific and mimic other surgical conditions, such as appendicitis and caecal diverticulitis.¹⁹ In our study the most common preoperative diagnoses were acute abdomen of uncertain origin (n =12), acute diverticulitis (n = 5) and acute appendicitis (n = 4).  Patients with foreign body perforations in the stomach, duodenum, and large intestine are significantly more likely to be febrile with chronic symptoms with a normal total white blood cell count compared to those with foreign body perforations in the jejunum and ileum.¹⁸   Plain radiographs of neck and chest in both anteroposterior and lateral views are required in all cases of suspect foreign body ingestion and perforations in addition to abdominal films. CT scans are more informative especially if radiographs are inconclusive.²⁰ Computerised tomography (CT) scanning and ultrasonography can recognise radiolucent foreign bodies. An ultrasound scan can directly visualize foreign bodies and abscesses due to perforation. The ability to detect a foreign body depends on its constituent materials, dimensions, shape and position.²¹ Contrast studies with Gastrograffin may be required in excluding or locating the site of impaction of the foreign body as well as determining the level of a perforation. Using contrast is important in identifying and locating foreign bodies if intrinsically non-radiopaque substances, such as wooden checkers or fish and chicken bones are ingested.²⁰ The high performance of computed tomography (CT) or multi-detector-row computed tomography (MDCT) scan of the abdomen in identifying intestinal perforation caused by foreign bodies has been well described by Coulier et al. ²² Although, in some cases imaging findings can be nonspecific, however, the identification of a foreign body  with an associated mass or extraluminal collection of gas in patients with clinical signs of peritonitis, mechanical bowel obstruction, or pneumoperitoneum strongly suggests the diagnosis.^8,20 Finally, endoscopic examination, especially in the upper gastrointestinal tract, can be useful in diagnosis and management of ingested foreign bodies.

Whenever a diagnosis of peritonitis subsequent to foreign body ingestion is made, an exploratory laparotomy is performed. However, laparoscopically assisted, or complete, laparoscopic approaches have been reported.^17,23 The treatment usually involves resection of the bowel, although occasionally repair has been described.⁸  The most common treatment was simple suture of the defect. ²⁴ Once the foreign body passes the esophagogastric junction into the stomach, it will usually pass through the pylorus²⁵; however, surgical removal is indicated if the foreign body has sharp points or if it remains in one location for more than 4 to 5 days especially in the presence of symptoms. A decision should be based on the nature of the foreign body in those cases, as to whether a corrosive or toxic metal in ingested. ²⁶ Occasionally, objects that reach the colon may be expelled after enema administration. However, stool softeners, cathartics and special diets are of no proven benefit in the management of foreign bodies.⁷

Introduction:

Total knee replacement (TKR) is an effective and cost-effective intervention for advanced osteoarthritis (OA). Pain is the main indication for the procedure, and the majority of patients undergoing a TKR gain significant pain relief ^1-3.

However, an important minority of those who undergo a TKR have persistent pain in the operated knee ⁴. Baker showed that 19.8% of patients with data in the National Joint Registry had persistent knee pain, and 18.2% were dissatisfied with the procedure ⁵. Anderson, in a study of 98 patients, found that 8.1% claimed that the operated knee was worse at follow-up (2-3 years after surgery) than prior to surgery and 9.2% were dissatisfied Wylde et al reviewed the available literature in 2009, and found that 10-20% of patients report significant pain in the operated knee, and that the patient centred outcomes of TKR appear to be considerably worse than those of total hip replacement, where as implant survivorship figures are fairly similar ⁷.

There are numerous possible causes of pain after a TKR, including anterior knee pain arising from the patello-femoral joint and extensor apparatus, prosthesis loosening, or infection. Other likely causes include soft-tissue periarticular problems, referred pain, pain sensitisation, or neuropathic painBecause of the risk of infection, and the possible need for further surgery, orthopaedic surgeons are generally keen to investigate these patients thoroughly and exclude surgical causes of the problem. However, there seems to be background pain vulnerability in the knee causing this high incidence of post-operative pain. The pain itself clearly needs appropriate management but patients also need surgical evaluation to exclude important reversible causes.⁹

In spite of this being a sizeable and worrying problem in orthopaedics, very little has been written about the assessment or management of these patients. No protocols or guidelines are available and the costs of management have not been explored.

In this paper we describe the first case series of patients with chronic knee pain after a TKR, and document the investigations and treatment undertaken, and the direct financial costs of their care to the NHS Trust in which they were seen.

RD&E provides an Arthroplasty tertiary referral service for a large area but is a large District General Hospital and as such the costs and results we report should be representative of most trusts within the UK

Methods:

A specialist service for revision knee surgery is available at the Royal Devon and Exeter Hospital, resulting in the referral of patients with problems in a knee after a TKR. A registry of such patients has been established at the hospital. The data presented here is based on examination of the records of 41 of these patients. These were patients with a painful TKR who had been referred to one of the authors from Orthopaedic specialists in various institutions including the resident hospital.

The notes of these patients were analysed to ascertain the number of appointments patients’ had attended to address the TKR problem, and what investigations and treatments had been undertaken for that problem both by the originating surgeon and by the revision knee specialist.

In addition data was obtained from the Trust on the current costs of the clinic appointments, investigations and any treatment or interventions undertaken.

Results:

The 41 patients studied included 27 women and 14 men, with a mean age of 63.9 years (range 49-81) at time of initial TKR. In the year 2009, 536 TKR’s were performed in the trust with an average age of 70.5 years (range 37-94) with 298 females and 238 males.

Investigations were commenced for abnormal pain post total knee replacement on average 15 months (range 1-84) after their knee replacement. Appointments and investigations were undertaken over a mean time of 20 months from initial investigation (range 7-45).

Neuropathic pain was diagnosed in 6 patients and instability was identified as a cause in 5 patients. 4 patients suffered aseptic loosening and no diagnosis was made in 26 patients (63%).

Table 1 shows the average number of appointments attended and investigations undertaken on these 41 patients.

Data on the costs of these appointments, investigations and treatments to the local NHS Trust are presented in Table 2.

Table 1- Number of appointments and investigations per patient with a painful TKR

Table 2 – Costs of appointments, investigations and treatments per patient

*= X-ray radiographs costs were insignificant and not charged to the NHS Trust

The outcomes of these 41 patients included medical management alone in 19 (14 of whom reported significant improvement) and further surgical interventions in 22 (14 of whom reported improvement). The calculated direct costs of investigation and management of those treated solely medically (i.e. non-surgically) was £190/patient, while the cost of those treated surgically was £5,051/patient. This is shown in table 3.

Table 3 – Comparison of operative versus non-operative costs

Discussion:

We have analysed the management of a case series of patients with persistent pain in the knee after TKR. The results show that most of the 41 people studied attended numerous appointments with different specialists, and had the same investigations (serology and x-rays) repeated on many occasions over a relatively short period of time (less than 2 years), often before referral to a surgeon with a specific revision knee interest. We have also shown that the investigations and treatment undertaken were costly to the NHS, particularly if specialist imaging investigations (CT or MRI) or further surgical procedures (including aspiration or arthroscopy) were undertaken. The costs to the patients of the numerous appointments and repeated investigations have not been included, but are likely to have been considerable.

The fact that many different appointments were offered, and many investigations repeated, along with the wide range of different approaches to the different patients, are indicative of the absence of clear patient pathways or of a co-ordinated clinical service for these patients. Patients were seen by orthopaedic surgeons, pain specialists and physiotherapists, but definitive diagnoses or management plans did not often result from these appointments, and investigations were often repeated unnecessarily. We do not believe that this situation is unique to our area, as there are no clear guidelines or protocols to help us know how best to investigate or manage these patients before referral and the natural history of the condition is unknown.

The investigations carried out most frequently were serological tests (ESR and CRP) to try to exclude infection, and x-rays to look for prosthesis loosening or other bony problems. Previous work has shown that a single test of ESR greater than 22.5 or CRP greater than 13.5, in this situation, has a sensitivity of 0.77 and a specificity of 0.93 for the diagnosis of infection Repeating these tests offers little help, and if these were positive it would seem more appropriate to proceed to joint aspiration ^{11, 12-15}.

Similarly, there is little point in doing more than one x-ray study a year, as the rate of change in radiographic findings is slow. If a bone problem is suspected, other more sophisticated imaging modalities can be used ^16-18.

The cost data obtained from our Trust show that high costs are incurred from new clinic referrals and visits, sophisticated imaging procedures (CT, MRI and bone scans), and surgical procedures – in particular revision surgery. These high costs of investigations would indicate that patients with a painful TKR would be more appropriately investigated and managed by specialist centres with early and meticulous evaluation by surgeons with a special interest in revision knee surgery.

The surgical costs of management of painful TKR’s dwarf the amount of money spent on medical (i.e. non-surgical) approaches. This considerable difference suggests that it is of paramount importance to manage the pain early, irrespective of whether surgery is required. Good pain management will allow the surgeon, and particularly the patient, to evaluate the problem in a clearer manner, weighing up the treatment options and making a decision from a more balanced position.

According to data from the National Joint Registry, over 53,000 TKRs were performed in NHS hospitals in England and Wales in 2009 ¹⁹. Using the estimates of Baker, and Wylde and others on the numbers of these patients who are in pain or dissatisfied, we calculate that over 10,000 patients each year, in this country alone, are acquiring the problem of persistent pain in a TKR ^,7This represents a huge public health problem, and one that, if our Trust’s cost figures are representative, is probably costing the NHS over £10 Million/annum. In view of that, we believe that this issue needs urgent attention from the research community and health care providers.

Figure 1 – Algorithm for assessment of a patient with a painful TKR

Our recommendation is that research is undertaken to document the natural history of pain in a TKR knee, differentiate the main causes of this pain, and develop simple algorithms to help clinicians make the correct diagnosis. We suggest a protocol that can be utilised by healthcare professionals to investigate painful TKR’s to allow correct assessment and diagnosis (Figure 1). We believe that health care providers in major orthopaedic centres should set up interdisciplinary clinics in which surgeons, pain specialists and physiotherapists can work together to help investigate and manage these patients.