2011

Introduction

Hepatitis B (HB) is a major disease and is a serious global public health problem. About 2 billion people (latest figures so far by WHO) are infected with the hepatitis B virus (HBV) all over the world. Interestingly, rates of new infection and acute disease are highest among adults, but chronic infection is more likely to occur in persons infected as infants or young children, which leads to cirrhosis and hepatocellular carcinoma in later life. More than 350 million persons are reported to have chronic infection globally at present^1,2. These chronically infected people are at high risk of death from cirrhosis and liver cancer. This virus kills about 1 million persons each year. For a newborn infant whose mother is positive for both HB surface antigen (HBsAg) and HB e antigen (HBeAg), the risk of chronic HB Virus (HBV) infection is 70% - 90% by the age of 6 months in the absence of post-exposure immunoprophylaxis³.

HB vaccination is the only effective measure to prevent HBV infection and its consequences. Since its introduction in 1982, recommendations for HB vaccination have evolved into a comprehensive strategy to eliminate HBV transmission globally⁴. In the United States during 1990–2004, the overall incidence of reported acute HB declined by 75%, from 8.5 to 2.1 per 100,000 population. The most dramatic decline occurred in children and adolescents. Incidence among children aged <12 years and adolescents aged 12-19 years declined by 94% from 1.1 to 0.36 and 6.1 to 2.8 per 100,000 population, respectively^2,5.

Population of countries with intermediate and high endemicity rates are at high risk of acquiring HB infection. Pakistan lies in an intermediate endemic region with a prevalence of 3-4% in the general population⁶. WHO has included the HB vaccine in the Expanded Programme on Immunisation (EPI) globally since 1997. Pakistan included the HB vaccination in the EPI in 2004. Primary vaccination consists of 3 intramuscular doses of the HB vaccine. Studies show seroprotection rates of 95% with standard immunisation schedule at 0, 1 and 6 months using a single antigen HB vaccine among infants and children^7,8. Almost similar results have been reported with immunisation schedules giving HB injections (either single antigen or in combination vaccines) at 6, 10 and 14 weeks along with other vaccines in the EPI schedule. But various factors like age, gender, genetic and socioenvironmetal influences, are likely to affect seroprotection rates⁹.So there is need to know actual seroprotection rates in our population where different vaccines, EPI procured and privately procured incorporated in different schedules are used. This study has been conducted to know the real status of seroprotection against HB in our children. Results will help in future policy-making, highlighting our shortcomings, comparing our programme with international standards and moreover augment future confidence in vaccination programmes.

Materials  And  Methods

This study was conducted at vaccinations centres and paediatrics OPDs (Outpatient Departments) of CMH and MH, Rawalpindi, Pakistan. Children reporting for measles vaccination at vaccination centres at 9 months of age were included. Their vaccination cards were examined and ensured that they had received 3 doses of HB vaccine according to the EPI schedule, duly endorsed in their cards. They included mainly children of soldiers but some civilians also who were invited for EPI vaccination at the MH vaccination centre. Children of officers were similarly included from the CMH vaccination centre and vaccination record was ensured by examining their vaccination cards. Some civilians who received private HB vaccination were included from paediatric OPDs . Some children beyond 9 months and less than 2 years of age who reported for non-febrile minor illnesses in the paediatric OPD at CMH and MH, were also included and their vaccination status was confirmed by examining their vaccination cards.

Inclusion Criteria

1) Male and female children >9 months and <2 years of age.

2) Children who had received 3 doses of HBV according to the EPI schedule at 6,10 and 14 weeks.

3) Children who had a complete record of vaccination- duly endorsed in vaccination cards.

4) Childen who did not have history of any chronic illness.

Exclusion Criteria  

1) Children who did not have proper vaccination records endorsed in their vaccination cards.

2) Interval between last dose of HBV and sampling was <1 month.

3) Children suffering from acute illness at time of sampling.

4) Children suffering from chronic illness or on immunosuppressive drugs.

Informed consent for blood sample collection was obtained from the parents or guardians. The study and the informed consent form was approved by the institutional ethical review board. Participants were informed about results of HBs antibody screening. After proper antiseptic measures, blood samples (3.5 ml) were obtained by venepuncture. Autodisabled syringes were used. Collected blood samples were taken in vaccutainers and labelled by identification number and name of child. Samples were immediately transported to the Biochemistery Department of Army Medical College. Samples were kept upright for half an hour and then centrifuged for 10 minutes. Supernatant serum was separated and stored at -20 ⁰C in 1.5 ml eppendorf tubes till the test was performed. Samples were tested using ELISA (DiaSorin S.p.A Italy kit) for detection of anti-HBs antibodies according to manufacturers’ instructions. The diagnostic specificity of this kit is 98.21% (95% confidence interval 97.07-99.00%) and diagnostic sensitivity is 99.11% (95% confidence interval 98.18-99.64%) as claimed by the  manufacturer. Anti-HBs antibody enumeration was done after all 3 doses of vaccination (at least 1 month after the last dose was received).

As per WHO standards, anti-HBs antibody titres of >10 IU/L is taken as protective and samples showing antibody titres <10 IU/L were considered as non-protected. Samples having antibody titres >10 IU/L were taken as seroprotected against HB infection. All relevant information was entered  in a predesigned data sheet and used accordingly at the time of analysis. Items entered included age, gender, place of vaccination, type of vaccination (private or government procured), number of doses and entitlement status (dependent of military personnel or civilian). The study was conducted from 1^st January 2010 to 31^st Dec 2010.

Statistical Analysis

Data was analysed using SPSS version 15. Descriptive statistics were used to describe the data, i.e. mean and standard deviation (SD) for quantitative variables, while frequency and percentages were used for qualitative. Quantitative variables were compared through independent samples’ t-test and qualitative variables were compared through the chi-square test between both the groups. A P-value <0.05 was considered as significant.

The mean age of the children was 13.7 months. The overall frequency of children with titres <10 IU/L was 61 (31.4%) while frequency of children with titres >10 IU/L was 133 (68.6%).

Geometric mean titres (GMT) were 85.81 for the seroprotected (>10 IU/L) category.

Results

One hundred and ninety-four children, who had received HB vaccination according to EPI schedule, were tested for anti-HBs titres. Out of them 61 (31.4%) had anti-HBs titres less than 10 IU/L (non-protective level) while 133 (68.6%) had anti-HBs titres above 10 IU/L (protective level) as shown in Figure 1. The GMT of anti-HBs among the individuals having protective levels (> 10 IU/L) was found to be 85.81 IU/L.

Figure 1

Figure 2

Figure 2 shows that anti-HBs titres between 10–100 IU/L was found in 75 (50.4%) children. Twenty-six (19.5%) individuals had titres between 100–200 IU/L. Twenty (14%) children had titres between 20–500 IU/L, 10 (7%) children had titres between 500–1000 IU/L and only 2 (1.5%) children had anti-HBs titres > 1000 IU/L.

One hundred and eighty-four children received vaccination supplied by government sources (Quinevaxem by Novartis) out of which 61 (33.1%) children had anti-HBs titres <10 IU/L (non- protective) and 123 (66.9%) had anti-HBs titres >10 IU/L (protective level). Only 10 children had received vaccination obtained from a private source (Infanrix Hexa by GSK), out of which all 10 (100%) had anti-HBs titres >10 IU/L (protective level). Comparison between the two groups revealed the difference to be significant (P value= 0.028).

One hundred and thirty-two children received vaccination from army health facilities (CMH and MH) out of which 36 (27.3%) had anti-HBs titres < 10 IU/L while 96 (72.7%) had anti-HBs titres >10 IU/L. Sixty-two children were vaccinated at civilian health facilities (health centres or vaccination teams visiting homes). Out of them 25 (40.3%) had anti-HBs titres <10 IU/L while 37 (59.7%) had anti- HBs titres >10 IU/L. The difference was insignificant (P value= 0.068). Gender analysis revealed that in the study group 129 (68.5%) were male children. Out of them 34 (26.4%) had anti-HBs titres <10 IU/L and 95 (73.6%) had anti-HBs titres >10 IU/L. Sixty-five (31.5%) were female children and out of them 27 (41.5%) had anti-HBs titres <10 IU/L while 38 (58.5%) had anti-HBs titres > 10 IU/L. Statistical analysis revealed the difference between males and females was significant (P value= 0.032).

One hundred and twenty-two (62.9%) children were less than 1 year of age. Out of them 37 (30.3%) had anti-HBs titres <10 IU/L and 85 (69.7%) had anti- HBs titres >10 IU/L. Seventy-two (37.1%) children ranged between 1 to 2 years of age. Out of them 24 (33.3%) had anti-HBs titres <10 IU/L while 48 (66.7%) had anti-HBs titres >10 IU/L. On comparison the difference between the two groups was insignificant (P value=  0.663), as shown in Table 1.

Table 1 (NS = Insignificant;  * = Significant )

Discussion

HB is a global health problem with variable prevalence in different parts of the world¹. Various studies carried out in different parts of Pakistan in different groups of population have shown diverse figures regarding prevalence of HB. However, a figure of 3-4% is accepted as general consensus by and large, thus making Pakistan an area of intermediate endemicity for HB⁶.  Yet when we extrapolate these figures to our population, it is estimated that Pakistan hosts about seven million carriers of HB which is about 5% of the worldwide 350 million carriers of HB^10,11.

Age at the time of infection plays the most important role in acquisition of acute or chronic HBV disease. HBV infection acquired in infancy is responsible for a very high risk of chronic liver disease due to HBV in later life¹². HB is a preventable disease and fortunately vaccination at birth and during infancy can eradicate the disease globally, if vaccination strategy is effectively implemented¹³. This can be claimed as the first anti-cancer vaccine which prevents hepatocellular carcinoma  in later life.

In Pakistan, the HB vaccine was included in the EPI in 2004, given along with DPT (Diphtheria, Pertussis, Tetanus) at 6, 10 and 14 weeks of age. The vaccine is provided through government health infrastructure to health facilities. Private HB vaccines supplied as a single antigen or in combination vaccines are also available in the market. The efficacy of these recombinant vaccines is claimed to be more than 95% among children and 90% among normal healthy adults¹⁴. The immunity of the HB vaccination is directly measured by development of anti-HBs antibodies more than 10 IU/L, which is considered as a protective level¹⁵. However, it is estimated that 5–15 % of vaccine recipients may not develop this protective level and remain non-responders due to undermentioned reasons.¹⁶ Published studies regarding antibody development in relation to various factors in terms of immunogenicity and seroprotection, show highly varied results. Multiple factors like dose, dosing schedules, sex, storage, site and route of administration, obesity, genetic factors, diabetes mellitus and immunosupression, affect HB antibodies development response¹⁷.

Although the HB vaccine was included in the EPI in 2004 in Pakistan, until now no published data showing seroconversion and seroprotection among vaccine recipients of this programme is available on a national level to our knowledge. Our study has revealed that out of 194 children, only 133 (68.6%) had anti-HBs titres in the protective range (>10 IU/L) while 61 (31.4%) did not develop seroprotection. These results are low as compared to other international studies. A study from Bangladesh among EPI vaccinated children shows a seroprotection rate of 92.2%¹³ while studies from Brazil¹⁸ and South Africa¹⁹ have separately reported seroprotection rates of 90.0% and 86.6%, respectively. Studies from Pakistan carried out in adults also show seroprotection rates (anti-HBe titres >10 IU/L) of more than 95% in Karachi University students¹⁴ and 86% in health care workers of Agha Khan  University Hospital²⁰, respectively. However, in these studies the dosing schedule was 0, 1 and 6 months, and participants were adults. These results are consistent with international reports.

The gravity of low seroprotection after HB vaccination is further aggravated when we extrapolate these figures to our overall low vaccination coverage rates of 37.6% to 45% as shown in studies at Peshawar and Karachi respectively^21,22. One can imagine a significantly high percentage of individuals vulnerable to HBV infection even after receiving HB vaccine in an extensive national EPI programme. Therefore, a large population still remains exposed to risk of HBV infection, and national and global eradication of HBV infection will remain a dream. Failure of seroprotection after receiving the HBV vaccination in the EPI will also be responsible for projecting a sense of false protection among vaccine recipients.

Dosing schedule is an important factor in the development of an antibody response and titre levels. According to the Advisory Committee on Immunization Practices (ACIP) of America, there should be a minimum gap of 8 weeks between the second and third doses and at least 16 weeks between the first and third doses of the HB vaccination²³. To minimize frequent visits and improve compliance, the dosing schedule has been negotiated in the EPI to 6, 10 and 14 weeks²⁴. Although some studies have shown this schedule to be effective, the GMT of anti-HBs antibodies achieved was lower than that achieved by the standard WHO schedule²⁵. This may be one explanation of lower rates of seroprotection in our study. The GMT achieved in our study among the children having protective levels of antibodies is 85.81 IU/L which is lower than most other studies. This supports the observation that GMT achieved in this schedule is lower than that produced by the standard WHO schedule. This may result in breakthrough infection of HB in vaccinated individuals in later life due to waning immunity. However, the immune memory hypothesis supports protection of vaccinated individuals in later life in spite of low anti-HBs antibody titres²⁶. Yet further studies are required to dispel this risk.

Another shortcoming of this schedule is to miss the dose at birth (‘0 dose’). It has been reported that the 0 dose of the HB vaccine alone is 70% - 95% effective as post-exposure prophylaxis in preventing perinatal HBV transmission without giving HB immunoglobulins²⁷. This may also be a factor contributing to lower rates of seroprotection in our study as we have not done HBsAg and other relevant tests to rule out HBV infection in these children. Moreover pregnant ladies by and large are not screened for HBV infection in Pakistan routinely in the public sector except in a few big cities like Islamabad, Lahore or Krachi. Therefore, we do not know the HB status of pregnant mothers and the risk of transmission to babies remains high. Different studies have reported much varied figures of HB status in pregnant ladies. A study from Karachi reports 1.57% pregnant ladies are positive for HBsAg while a study from Rahim Yar Khan reports this figure to be up to 20%^28,29. A study by Waheed et al regarding the transmission of HBV infection from mother to infants reports the risk to be up to 90%³⁰. All of these studies support the importance of the birth dose of the HB vaccination and augment the fact that control and eradication of HB with the present EPI schedule is not possible. Jain from India has reported a study using an alternative schedule of 0, 6 weeks and 9 months. He has reported it to be comparable to the standard WHO schedule of 0, 1, 6 months in regards to seroprotection and GMT levels achieved³¹. This schedule can be synchronised with the EPI schedule, avoiding extra visits and incorporating the birth dose. A similar schedule can also be incorporated in our national EPI.

In our study, seroprotection rates were found to be low in the female gender and the difference was significant. This finding differs with other studies which report lower seroprotection rates in males³². Although the number of female children was less,  there is no plausible explanation for this observation. The site of inoculation of the HB vaccine is also very important for an adequate immune response. Vaccines given in the buttocks or intradermally produce lower antibody titres than intramuscular injections given in the outer aspect of the thigh in children, due to poor distribution and absorption of the vaccine within the host body. The practice of giving vaccinations in the buttocks by vaccinators is a common observation which they feel convenient for intramuscular injection in children. This may also be one reason for low seroprotection rates in our study, as we picked the children at random who had received vaccination at public health facilities except a small number of private cases.          

The effectiveness of the vaccine also depends on the source of procurement and proper maintenance of the cold chain. In this study 100% seroprotection was observed in children who received the HB vaccine procured from a private source. Although the number of private cases was less, this factor of source and the cold chain also needs attention. To address this issue proper training of EPI teams regarding maintenance of temperature, injection techniques, motivation and monitoring can improve outcomes substantially.

The findings of this study are different from published literature because this is a cross-sectional observational study. This reports the actual seroprotection rates after receiving the HB vaccination in the EPI schedule. While most other studies show the results after ensuring control of influencing factors such as type of vaccine, dose, schedule, route of administration, training and monitoring of local EPI teams and health status of vaccine recipients, etc. Therefore, this is an effort to look at a practical scenario and evaluate outcomes which can help in framing future guidelines to achieve the goal of control and eradication of HB infection. Further studies are required at a large scale to determine the effect of HB vaccination at a national level.

Conclusion

The HB vaccination programme has decreased the global burden of HBV infection, but evidence of decreased burden is not uniform amongst world population.Of course figures witness marked decrease in developed world while in developing world statistics show little change. Unfortunately, implementation of this programme is not uniformly effective in all countries, thus resvoirs of infection and the source of continued HBV transmission persists. HBV infection is moderately endemic in Pakistan. The HB vaccine has been included in the national EPI since 2004. The present study shows seroprotection rates of only 68.6% in vaccine recipients, which is low when compared with other studies; 31.4% of vaccine recipients remain unprotected even after vaccination. Moreover GMT achieved in seroprotected vaccine recipients is also low (85.81 IU/L). There can be multiple reasons for these results, such as type of vaccine used, maintenance of the cold chain, route and site of administration, training and monitoring of EPI teams and dosing schedule. In present practice, the very important birth dose is also missing. These observations warrant review of the situation and appropriate measures to be taken to rectify the above mentioned factors, so that desired seroprotection rates after HB vaccination in the EPI can be achieved among vaccine recipients.

Introduction

A colonic diverticulum is defined as a sac-like protrusion of mucosa through the muscular component of the colonic wall¹. The terms “diverticulosis” and “diverticular disease” are used to express the presence of diverticula without associated inflammation. While the term “diverticulitis” indicates there is inflammation of a diverticulum or diverticula, which is commonly accompanied by either microscopic or macroscopic perforation².

In the developed world, diverticular disease of the colon is widespread and in those aged over 65 years of age it is present in greater than 65%³. The incidence increases dramatically with time and while only 5% of the western population are affected in the fifth decade this rises steeply  to over 50% by the eight decade and 60% in the ninth ⁴.

Although diverticulosis is extremely common, complications requiring surgery only occur in 1% of patients overall ⁵ and 10% of those admitted to hospital as an emergency for treatment⁶. Despite this, there is a substantial healthcare burden inflicted by diverticular disease and within the United States alone it accounts for 312,000 hospital admissions, 1.5 million days of inpatient treatment and a total estimated cost of 2.6 billion dollars per annum ⁷.

The aetiology of the diverticulosis is poorly understood but it is probably a multi-factorial process involving dietary habits (specifically low fibre intake) as well as changes in colonic pressure, motility and wall structure that are associated with ageing⁸. The pathogenesis of diverticulitis is also uncertain, however stasis or obstruction in a narrow necked diverticulum leading to overgrowth of pathogens and local tissue ischemia is thought likely ².

This review will discuss the common presentations, investigations and current treatment strategies utilised in the management of acute diverticulitis and its complications as well as providing an up to date synopsis of existing recommendations for follow up and prevention. 

Symptoms and Signs

In Western nations, diverticula are most commonly situated in the left colon⁹ and 99% of patients will have some element of sigmoid involvement¹⁰. Therefore patients commonly present with sigmoid diverticulitis that typically displays features of left iliac fossa pain and fever with raised inflammatory markers (see below). Physical exam will disclose left lower quadrant peritonism for simple disease, but in complicated cases physical examination findings may reveal a palpable abdominal mass, evidence of fistulas or obstruction, or widespread peritonitis¹¹.

In cases of complicated diverticulosis, a stricture may lead to obstructive symptoms with complaints of nausea, vomiting and distension being present. If a fistula has developed, a history of recurrent urinary tract infection, pneumaturia and faecaluria may also be elicited¹². In a female with a previous history of hysterectomy suspicion will be further raised as colovesical and colovaginal fistulas are rare in females with their uterus in place. If a patient reports passing stools per vagina, insertion of a vaginal speculum and inspection may confirm this latter diagnosis¹².

Differential diagnosis

The differential diagnosis for diverticulitis and its complications is extensive and includes irritable bowel syndrome, inflammatory bowel disease, ischaemic or infective colitis, pelvic inflammatory disease and malignancy. It is obviously most imperative to exclude the latter differential ⁴, particularly in the case of a stricture that is impassable on colonoscopy, as many of these specimens following resection (32% in one series¹³) will transpire to be adenocarcinoma⁴. It should also be noted that sigmoid diverticulitis may also masquerade as acute appendicitis if the colon is long and redundant or otherwise situated within the abdomen or pelvis such that the inflamed segment lies in the suprapubic region, right iliac fossa or McBurney’s point².

Complications

Although diverticulosis is present in nearly two thirds of the elderly population, the vast majority of patients will remain entirely asymptomatic. Even so, an estimated 20% of those affected will manifest symptomatology, mainly as diverticulitis, but  potentially with further complications of perforation, abscesses, fistulas, and obstruction, as well as bleeding per rectum⁶.

The European Association for Endoscopic Surgeons (EAES) developed a classification scheme based upon the severity of diverticulitis, which broadly classifies patients into either simple symptomatic or complicated disease (Table 1)¹⁴. Where an abscess or perforation develops the Hinchey classification is used as a staging tool and can provide prognostic information on the likely outcome (Table 2)¹⁵.

Table 1 - European Association for Endoscopic Surgeons classification system for diverticulitis ¹⁴

Table 2 – Hinchey classification of perforated diverticulitis ¹⁵

* Stage I has been divided into Ia Phlegmon and Ib confined pericolic abscess in later modifications^{38 72}
** Stage II has been divided into IIa abscesses amenable to percutaneous drainage and IIb complex abscess with or without fistula in later modifications^{14 73}

Perforation is probably the most feared complication and the annual prevalence of perforated diverticulitis within a northern European population is currently thought to stand at 3.8 per 100,000 of the population, which is a figure that is increasing¹⁶. Despite this only 1-2% of patients who attend for urgent assessment and treatment will have a gross perforation² but for 80% this will be their first presentation so a high index of suspicion is still required¹⁷.

Blood investigations

In clinical practice, inflammatory markers, commonly the White Blood Cell (WBC) count and C-Reactive Protein (CRP) level, are frequently employed to assist in diagnosing diverticulitis and its complications. In a recent retrospective study, a White Blood Cell (WBC) count >10,000/μL was present in 62% of patients with Computed Tomography (CT) confirmed diverticulitis and the presence of leukocytosis was significantly more common in patients with diverticulitis and associated perforation than without (86% v 65%, p=0.01)¹⁸.

CRP has also been shown to be of considerable benefit in the diagnosis of acute left sided colonic diverticulitis ¹⁹. A recently established diagnostic nomogram with a reported accuracy of 86%  that was developed to improve the clinical diagnosis of diverticulitis includes an elevated CRP >50mg/l as well other variables including  age, previous episodes, aggravation of pain on movement, absence of vomiting and localization of symptoms and tenderness in the left iliac fossa¹⁹.

In addition, it has been demonstrated that in acute sigmoid diverticulitis a CRP below 50mg/l is unlikely to correlate with an associated perforation (negative predictive value 79%) while a CRP above 200mg/l is an indicator that the patient may have a perforation (positive predictive value 69%)²⁰. In this latter study, CRP also had the highest diagnostic accuracy in diagnosing perforation in acute sigmoid diverticulitis across a range of parameters assessed that included WBC count as well as less commonly used tests like bilirubin and alkaline phosphatase²⁰.

Imaging investigations

In the acute phase of diverticulitis the extent of the extramural component of inflammation is more important than the degree of the intramural inflammation and as such CT associated with the use of intravenous and oral contrast and, in ideal conditions, rectal contrast is the gold standard means of investigation²¹.

CT can accurately identify extra-luminal complications such as an abscess, phlegmon, adjacent organ involvement, or fistula, as well as recognising other alternative diagnoses such as appendicitis, pelvic inflammatory disease, tubo-ovarian abscess or inflammatory bowel disease²².

The two most frequent signs of diverticulitis on CT are bowel wall thickening (96%) and fat stranding (95%) (Figure 1) with less common but highly specific signs including fascial thickening (50%), free fluid (45%), and the presence of inflamed diverticula (43%) ²³. Specifically, abscess formation (Figure 2a and b) and extracolonic air or contrast (Figure 3a and b) are findings that are known to predict severity as summarised in the CT classification system developed by Ambrosetti et al ²⁴.

Figure 1 - Sigmoid diverticulitis: sigmoid colon with multiple diverticula, significant mural thickening (arrow) and pericolic fat stranding (circles)

Figure 2a - Sigmoid diverticulitis with abscess formation: sigmoid colon displaying diverticulosis mural thickening, and pericolic fat stranding (arrow). Adjacent low attenuation, septated collection (circle) representing abscess formation.

Figure 2b - Sigmoid diverticulitis with abscess formation: sigmoid colon displaying mural thickening, diverticulosis and pericolic fat stranding (arrow). Adjacent low attenuation, septated collection (circle) representing abscess formation, with adhesion noted to adjacent small bowel loops.

Figure 3a - Perforated sigmoid diverticulitis: sigmoid colon displaying diverticulosis and mural thickening (arrow) with adjacent collection of intra-abdominal free air and adjacent inflammatory fat stranding (circle), representing active diverticulitis with perforation.

Figure 3b - Perforated sigmoid diverticulitis: sigmoid colon displaying diverticulosis, mural thickening and pericolic inflammatory fat stranding (arrow) with adjacent collection of intra-abdominal free air and adjacent inflammatory fat stranding (circle), again representative of active diverticulitis with perforation.

However despite CT having a reported sensitivity of 97%, specificity of 98%, and global accuracy of 98%²⁵, a misdiagnosis of diverticulitis in cancer patients is relatively common and occurs in 5% of cases²¹. Therefore investigation of the colonic lumen by endoscopic means or barium enema after the acute attack is mandatory⁴ but avoided in the initial stages for fear of perforation and exacerbation of the disease².

In expert hands ultrasound is the next best alternative investigation with a reported sensitivity of 94%²⁶. It has been supported by a recent systematic review²⁷ as well as current practice guidance⁴ and in critically ill patients it avoids the use of intravenous and intra-luminal contrast²¹. However it is rarely used in practice as it is operator dependent²¹ and for it to be accurately utilised it requires a highly skilled/trained individual to be available at all times²⁸.

The other practical alternative  to CT is a hydro-soluble contrast enema, however this investigation is significantly inferior both in terms of sensitivity (98 v 92%, p<0.01) and evaluation of the severity of inflammation (26 v 9%, p<0.02)²⁹. While Magnetic resonance imaging (MRI) has a good sensitivity of 94% and a specificity of 87%³⁰, in the acute setting it may be impractical both in terms of examination time and patient co-operation²¹. Finally, laparoscopy can also be helpful for diagnostic purposes but again in practical terms, with the increasing availability of cross-sectional imaging, it is rarely required for this purpose⁴.

Outpatient treatment

Evidence for successful and economical outpatient treatment of uncomplicated diverticulitis is beginning to emerge. In a prospective study of 70 patients classified on the basis of an ultrasound examination as having mild-to-moderate acute colonic diverticulitis (as defined by either limited inflammation within a diverticulum extending up to an abscess < 2 cm in diameter), 68 patients were successfully treated with oral antibiotics with an initial liquid diet and this led to a cost saving on inpatient treatment of 80%³¹.

In a further retrospective analysis, among a cohort of patients who were referred for outpatient treatment it was found that such treatment was effective for 94% of patients, with women and those with free fluid on CT scan appearing to be at higher risk for treatment failure³².

In reality the prospect of outpatient treatment in uncomplicated cases of acute diverticulitis is determined largely by access to the necessary investigative tools for accurate diagnosis and staging of disease, the general fitness of the patient, their ability to maintain adequate oral intake, the possibility of further outpatient review, patient compliance with medications, satisfactory social support and ability to plan for endoscopic follow up²¹.

In broad terms, if symptoms are not severe and the patient has no significant co-morbidities and is compliant with medical treatment, then a course of broad spectrum antibiotics can be administered orally on an outpatient basis and the patient followed up at subsequent outpatient clinics. However if the patient is systemically unwell, elderly, has significant co-morbidities or there are any other concerns it is safer to arrange for a hospital admission and treatment with intravenous antibiotics¹².

Conservative inpatient treatment

Simple diverticulitis requiring hospital admission is usually treated by rehydration, symptomatic relief and intravenous antibiotics. Most patients with uncomplicated disease respond well to medical treatment and generally experience significant improvement in their abdominal pain, temperature and inflammatory markers within two days of initiation of antibiotic treatment³³. If this is not the case or there is clinical concern a repeat CT is advocated and operative intervention or percutaneous drainage considered (see below)².

It should be noted at this stage while the use of broad spectrum antibiotics in acute uncomplicated diverticulitis is supported by guidelines³⁴ there is no actual evidence mandating the routine use of antibiotics in mild uncomplicated diverticulitis³⁵ and in some European countries it is not routine³⁶.

High-quality evidence regarding the most effective type of antibiotic is also lacking³⁵. However anaerobic bacteria (usually bacteroides, clostridium, fusobacterium and peptostreptococcus) are the most commonly cultured organisms with gram-negative aerobes, especially Escherichia coli, and facultative gram-positives, such as streptococci, often grown as well³⁷. Therefore coverage against both Gram-negative and anaerobic bacteria is widely advocated^{2 21 38}.

If combination antibiotics are selected, Metronidazole provides excellent anaerobic cover with less risk of clostridium difficle infection than alternatives⁴. However use of single agent may be more cost effective³⁹. Local protocols are likely to influence selection but the patient may be safely switched from intravenous to oral therapy when they can tolerate a diet and oral medicines²² as intravenous antibiotics are not felt to be vastly superior⁴⁰. Seven to ten days of antibiotic therapy is an acceptable treatment period²² however evidence is emerging to support shorter courses⁴¹.

Elective surgery 

In a recent position statement from the Association of Coloproctology of Great Britain and Ireland (ASCPGBI) it was concluded that the majority of patients, whether young or old, presenting with acute diverticulitis could be managed with a conservative, medical approach in the longer term. Previous blanket recommendations for elective resection e.g. following two acute episodes of diverticulitis¹⁴ were challenged in this statement and it was proposed that the decision on elective resection should be made on an individual basis⁴. The traditional practice of waiting for a period of 4-6 weeks after a diverticulitis attack before performing an elective operation was not disputed¹².

Surgery in the elective setting can be by either an open or laparoscopic technique with a recent randomised trial identifying a 27% reduction in major morbidity⁴² along with less pain, improved quality of life and shorter hospitalization at the cost of a longer operating time with the laparoscopic approach⁴³. In expert centres conversion rates as low as 2.8% and median hospitals stays of 4 days can be achieved⁴⁴ and individual case reports of resections using single laparoscopic port access have also emerged⁴⁵.  However if a laparoscopic resection is considered, it is currently recommended that patients should be treated after full recovery from the acute episode of inflammation as there is evidence to suggest lower complication and conversion rates can be achieved⁴.

The principles for both approaches are the same. A colorectal anastomosis is a predictor of lower recurrence rates after elective sigmoid resection for uncomplicated diverticulitis⁴⁶. Therefore it is recommended that the distal resection margin is taken onto the rectum as opposed to the distal sigmoid and the splenic flexure is fully mobilised to facilitate this⁴, however in the case of a long redundant left colon this may not be necessary¹². The proximal resection margin is less clear but should be made onto soft compliant bowel^{4 34}. Often it is possible to identify the ureters intra-operatively however, there may be cases of complicated diverticulitis in which the extent and degree of inflammatory changes warrant the use of pre-operatively placed ureteric stents to help aid their identification and avoid injury¹².

Emergency surgery for complicated diverticulitis

The indications for emergency operative intervention in acute diverticulitis include the presence of generalised peritonitis, uncontained visceral perforation, gross uncontrollable sepsis, a large undrainable or inaccessible abscess, bowel obstruction and lack of improvement or clinical deterioration with initial medical management ².

Historically, perforated diverticulitis was treated with a three-stage procedure consisting of faecal diversion with a stoma, resection of the diseased segment of bowel, followed by takedown of the stoma and restoration of intestinal continuity. This then shifted to performing a Hartmann’s procedure which includes a primary resection of the diseased segment and end colostomy followed by subsequent colostomy reversal at a second operation¹¹. In this case reconstruction generally involves a second laparotomy because although laparoscopic reconstruction is effective, it is infrequently performed^47-48. As a result reversal is often permanently deferred. 

In selected cases the ideal therapeutic option in colonic perforation is a one-stage procedure with resection followed by primary anastomosis, which adds the benefits of being a definitive treatment with the avoidance of the morbidity and mortality associated with a stoma and its reversal⁴⁹. A protective ileostomy after resection and primary anastomosis is viewed as a valid additional step in patients at high risk of an anastomotic leak (immunosuppression, American Society of Anaesthesiologists (ASA) grade IV, faecal peritonitis)²¹ but a Hartmann’s procedure may also be selected.

Particularly in cases where there is a stricture causing obstruction and significant faecal loading, a resection in conjunction with on-table colonic lavage and primary anastomosis may be used. This technique has also been described as facilitating a primary anastomosis in the case of a perforation⁵⁰.  However in certain patients with obstruction depending on the viability of the proximal colon a subtotal colectomy with ileorectal anastomosis may be required¹² and because small-bowel obstruction may also occur, especially in the presence of a large diverticular abscess, this may also warrant further treatment².

The use of endoscopic colonic stenting as a treatment of acute obstruction of the large bowel secondary to colonic cancer has been well documented in the literature either as a definitive procedure or as a bridge to surgery and can effectively decompresses the obstructed colon in 90% of cases⁵¹.  However the use of stents in benign disease is less well documented , with it used mainly as a bridge to surgery⁵² and because is associated with a higher incidence of complications in acute diverticular disease⁵³ it cannot as yet be recommended.

Laparoscopic surgery in the emergency setting

There have been a number of recent reports of laparoscopic lavage with or without the placement of an intra-abdominal drain for patients with acute diverticulitis and perforation, with the reported advantages including the avoidance of an acute resection and the possibility of a stoma ⁴. The evidence that has been produced thus far to support its case is highly promising.

A recent systematic review of laparoscopic lavage for perforated colonic diverticulitis identified two prospective cohort studies, nine retrospective case series and two case reports with 231patients and the vast majority of patients (77%) had Hinchey grade III purulent peritonitis. Laparoscopic peritoneal lavage successfully controlled abdominal and systemic sepsis in 95.7% of patients, mortality was 1.7%, morbidity 10.4% and only four (1.7%) patients received a colostomy⁵⁴.

In the largest series in the literature to date, Myers et al reported 100 patients with perforated diverticulitis and generalised peritonitis. Eight patients with Hinchey IV disease required conversion to an open procedure, with the overall mortality being 4% and recurrence rates only 2% over a median time period of 36 months⁵⁵.

Percutaneous therapy

The appropriate management of diverticular abscesses is a matter of some debate. However according to the American Society of Colon and Rectal Surgeons (ASCRS) radiologically guided percutaneous drainage is usually the most appropriate treatment for patients with a large diverticular abscess as it avoids the need for emergency surgery and possibility of a colostomy³⁴.

When the abscess diameter is over 5 cm, percutaneous CT guided drainage, in combination with antibiotics, is the standard treatment and offers rapid improvement in symptoms in over 90% of cases, albeit with a high recurrence rate in more severe cases³⁸ and higher likelihood of surgery being needed in those involving the pelvis⁵⁶.

In practical terms diverticular abscesses less than 3 cm in diameter usually cannot be successfully drained, as the diameter of the pigtail of most drainage catheters will be a similar dimension²⁸. Also for smaller abscesses²¹, especially those less than 2cm resolution usually occurs with the use intravenous antibiotics alone³⁴. However if a drain is sited it is advisable that before it is removed, resolution of the abscess should be confirmed and a potential bowel fistula excluded by a further contrast study²⁸.

Finally, diverticular disease of the colon is also a relatively common cause of acute lower gastrointestinal bleeding and is in fact the diagnosis in 23% of cases⁵⁷. This usually settles with conservative management but if the bleeding is profuse angiography and endovascular intervention may be helpful, with surgery very rarely required for this indication⁴.

Follow up

Following successful medical management of an acute episode of diverticulitis, colonoscopy, flexible sigmoidoscopy or barium enema should be performed several weeks after the resolution of symptoms to confirm the diagnosis and rule out other colonic pathology such as malignancy, inflammatory bowel disease, or ischemia²².

Following surgery there is reported to be a high incidence of the order of 25% for recurrent symptoms, which is put down to the diagnostic overlap that exists with irritable bowel syndrome⁵⁸. However any suspicion of recurrent diverticulitis following surgical resection should be confirmed by CT scan after which antibiotic treatment should be initiated, as for a case of primary uncomplicated disease¹². If this is excluded the high incidence (17.6%) of symptomatic anastomotic stenosis after elective laparoscopic sigmoidectomy should be borne in mind with the possibility of endoscopic dilatation considered if applicable⁵⁹.

Lifestyle modifications and prevention

Following treatment weight loss, rationalisation of certain medications and exercise are recommended as obesity is significantly associated with an increased incidence of both diverticular bleeding and diverticulitis⁶⁰, as are non-steroidal anti-inflammatory drugs and paracetamol⁶¹, with physical activity significantly associated with a reduction in the risk of complications⁶².

Whilst dietary fibre, particularly cellulose⁶³, is recommended²² the evidence that supports these recommendations is not particularly strong⁶⁴. However foodstuffs such as nuts, seeds, popcorn and corn that are usually discouraged have no evidence to support the theory that they may lead to increased complications⁶⁵.

Small studies without control groups suggest that probiotics may have a positive effect on the recurrence of symptomatic diverticular disease^66-67. Long term administration of the non-absorbable antibiotic Rifaxamin has also been used with reported success⁶⁸ as has the anti-inflammatory mesalazine⁶⁹.  However none of these medications have a strong evidence base and as a result are not in routine use⁷⁰.

Introduction:

The clinical features of early HAT are well defined, yet the features of delayed HAT are less clear. Delayed HAT is a rare complication of OLT that may present with biliary sepsis or remain asymptomatic. Sonography is extremely sensitive for the detection of HAT in symptomatic patients during the immediate postoperative period. However, the sensitivity of ultrasonography diminishes as the interval between transplantation and diagnosis of HAT increases due to collateral arterial flow. MRA is a useful adjunct in patients with indeterminate ultrasound exams and in those who have renal insufficiency or an allergy to iodinated contrast.

In the absence of hepatic failure, conservative treatment appears to be effective for patients with HAT but retransplantation may be necessary as a definitive treatment.

Case Presentation:

A 52 year old male with a history of whole graft OLT for primary sclerosing cholangitis presented with two days of fever, nausea, and mild abdominal discomfort.

One week prior to presentation, he was seen in the liver clinic for regular follow-up. At that time, he was totally asymptomatic and his laboratory workup including liver function tests were within normal range.

He has undergone OLT three years prior. At the time of transplant he required transfusion of 120 units of packed red blood cells, 60 units of fresh frozen plasma and 100 units of platelets due to extensive intraoperative bleeding secondary to chronic changes of pancreatitis and severe portal hypertension, but had an otherwise uneventful postoperative recovery.

On physical examination the temperature was 39C, heart rate was 125 beats per minute, respiratory rate was 22 bpm. Initial laboratory workup revealed a white blood cell count of 25,000/mm³, AST of 6230 U/L, ALT of 2450 U/L, total bilirubin of 11 mg/dL , BUN 55 mg/dL and Creatinine of 4.5 mg/dL. Lactate level was 5 mmol/L. Doppler ultrasonography revealed an extensive intrahepatic gas (Image 1A). Computed tomography of the abdomen and pelvis revealed extensive area of hepatic necrosis with abscess formation measuring 19x14 cm with extension of gas into the peripheral portal vein branches (Image 1B,C). Upon admission to the hospital, the patient required endotracheal intubation, mechanical ventilator support and aggressively fluid resuscitation. He was started on broad-spectrum antibiotics and a percutaneous drain was placed that drained dark, foul smelling fluid.  Cultures from the blood and the drain grew Clostridium perfringens.

Magnetic resonance imaging (MRI), MRA revealed occlusion of the hepatic artery 2 cm from its origin and also evidence of collaterals (Image 2A,B).

Image 1: (Pannel A) Doppler ultrasonography reveal extensive intrahepatic gas. (Pannel B&C) Computed tomography of the abdomen and pelvis reveal an extensive area of hepatic necrosis with abscess formation measuring 19x14 cm with extension of gas into the peripheral portal vein branches.

Image 2: MRI & MRA reveal occlusion of the hepatic artery 2 cm from its origin and also evidence of collaterals.

Following drain placement, the patient’s clinical condition markedly improved with significant reduction of liver function test values. Retransplantation was considered but delayed in the setting of infection and significant clinical and laboratory testing improvement.

The patient was transferred to the medical floor in stable condition, and the drain was then removed.

A week later the patient developed low grade fevers and tachycardia. One day later he began to experience mild abdominal discomfort and high grade fevers. Repeat CT of the abdomen revealed worsening hepatic necrosis and formation of new abscesses. His clinical condition decompensated quickly thereafter requiring endotracheal intubation, mechanical ventilation and aggressive resuscitation. Percutaneous drain was placed and again, drained pus-like, foul-smelling material. His overall condition deteriorated, and he eventually expired a few days later.

Discussion:

Delayed (more than 4 weeks after transplantation) HAT is a rare complication of OLT with an estimated incidence of at around 2.8%¹.

Risk factors associated with development of HAT include Roux-en-Y biliary reconstruction, cold ischaemia and operative time, the use of greater than 6 units of blood, the use of greater than 15 units of plasma, and the use of aortic conduits on arterial reconstruction during transplant surgery².

Collateralization is more likely to develop after Live Donor Liver Transplantation (LDLT) than after whole-graft cadaveric OLT³. Therefore, the latter is also associated with increased risk of late HAT.

Although the clinical features of early HAT are well described, the features of delayed HAT are less clearly defined¹: the patient may present with manifestations of biliary sepsis or may remain asymptomatic for years. Right upper quadrant pain has been reported to occur in both immediate and delayed HAT. The clinical presentations may include recurrent episodes of cholangitis, cholangitis with a stricture, cholangitis and intrahepatic abscesses, and bile leaks¹. Doppler ultrasonography has been extremely sensitive for the detection of HAT in symptomatic patients during the immediate postoperative period but becomes less sensitive as the interval between transplantation and diagnosis of HAT increases because of collateral arterial flow⁴.

3D gadolinium-enhanced MRA provides excellent visualization of arterial and venous anatomy with a fairly high technical success rate. MRA is a useful adjunct in patients with indeterminate ultrasonography examination in patients who have renal insufficiency or who have allergy to iodinated contrast ⁵.

Antiplatelet prophylaxis can effectively reduce the incidence of late HAT after liver transplantation, particularly in those patients at risk for this complication⁶. Vivarelli et al reported an overall incidence of late HAT of 1.67%, with a median time of presentation of 500 days; late HAT was reported in 0.4% of patients who were maintained on antiplatelet  prophylaxis compared to 2.2% in those who did not receive prophylaxis⁶. The option of performing thrombolysis remains controversial. Whether thrombolysis is a definitive therapy or mainly a necessary step in the proper diagnosis of the exact etiology of HAT depends mostly on the particular liver center and needs further analysis⁷. Definitive endoluminal success cannot be achieved without resolving associated and possible instigating underlying arterial anatomical defects. Reestablishing flow to the graft can unmask underlying lesions as well as assess surrounding vasculature thus providing anatomical information for a more elective, better plan and definitive surgical revision⁷. Whether surgical revascularization compared to retransplantation is a viable option or only a bridging measure to delay the second transplantation has been a longstanding controversy in the treatment of HAT.

Biliary or vascular reconstruction do not increase graft survival and ongoing severe sepsis at the time of re-graft results in poor survival⁷. However, although uncommon, delayed HAT is a major indication for re-transplantation⁷. In the absence of hepatic failure, conservative treatment appears to be effective for patients with hepatic artery thrombosis.

C. perfringensis an anaerobic, gram-positive rod frequently isolated from the biliary tree and gastrointestinal tract. Inoculation of Clostridium spores into necrotic tissue is associated with formation of hepatic abscess⁸.

Necrotizing infections of the transplanted liver are rare. There have been around 20 cases of gas gangrene or necrotizing infections of the liver reported in the literature. Around 60% of these  infections were caused by clostridial species with C. perfringens accounting for most of them. Around 80% of patients infected with Clostridium died, frequently within hours of becoming ill^9,10. Those who survived underwent prompt retransplantation and the infection had not resulted in shock or other systemic changes that significantly decreased the likelihood of successful retransplantation⁸.

Because the liver has contact with the gastrointestinal tract via the portal venous system, intestinal tract bacteria may enter the liver via translocation across the intestinal mucosa into the portal venous system. Clostridial species can also be found in the bile of healthy individuals undergoing cholecystectomy^9,10.

The donor liver can also be the source of bacteria. Donors may have conditions that favor the growth of bacteria in bile or the translocation of bacteria into the portal venous blood. These conditions include trauma to the gastrointestinal tract, prolonged intensive care unit admissions, periods of hypotension, use of inotropic agents, and other conditions that increase the risk of potential infection ^8,9,10. C. perfringens sepsis in OLT recipients has been uniformly fatal without emergent retransplantation. Survival from C. perfringens sepsis managed without exploratory laparotomy or emergency treatment has been extremely rarely reported⁸. In those patients who survived, and in whom the infection has not resulted in shock or multiple organ failure, retransplantation may be successful⁸.

Although our patient survived his intensive care course, his recovery was tenuous as he quickly developed additional hepatic abscesses that led to his eventual demise. Post-mortem examination in our patient revealed intra-hepatic presence of Clostridium perfringens.

He was managed conservatively since he markedly improved both clinically and by liver function tests. Because of this, retransplantation was delayed. He was also already on antiplatelet prophylaxis.

Conclusion:

We report an interesting case of Clostridium perfringens hepatic abscess due to late HAT following OLT. Although the patient initially improved with non-surgical treatment, he eventually died. In similar cases, besides aggressive work-up and medical management retransplantation may be necessary for a better long term outcome.

Introduction:

Payment by results was introduced across the National Health Service (NHS) in 2005. It’s aim was to provide a pricing structure (tariff) for the whole country with some allowance for geographical variation^1-2. The system uses Healthcare Resource Group codes (HRG) in which treatments in similar cost brackets have the same codeA price / tariff is derived from each hospital patient episode and the patient’s registered Primary Care Trust (PCT) is billed accordingly.

In order to generate an HRG code data is collected by the hospital clinical coding department including primary diagnosis, comorbidity (which incurs an extra charge if applicable), and complications, surgical procedure, age and duration of stay⁴. Diagnoses (either primary, co morbidities or complications) are coded using ICD-10 codes. Surgical procedure is defined using OPCS-4 codesA piece if software is then utilised to allocate the HRG code. Each HRG code represents a tariff, which is the average cost of a treatment nationwide. Minor regional adjustments are made to reflect the cost of living².

Payment by results covers all admissions, attendance in accident & emergency departments and outpatients attendances⁵. The 2004 NHS Improvement plan designated 18 weeks as a target for referral to treatment (RTT)⁶. It is a common misconception that trauma patients do not account for considerable income within the NHS. Trauma is often seen as the poor relation when compared with elective work where a target based culture now prevails. Elective targets must be met or hospital trusts can incur financial penalty. This situation is not apparent for trauma due to the acute nature of service delivery in the majority of cases. The burden of trauma work can block elective admissions and is seen by some as a barrier to target attainment. At least 36% of orthopaedic surgeons in the United Kingdom describe trauma as part of their sub-specialist interestWe aimed to assess the throughput and income generated from one week of trauma workload and compared this with the elective throughput in our unit for the same week. This was performed by means of a prospective study. We are not aware of any published work in this specific area.

Methods:

We followed all acute patients admitted to our trauma unit between 21/02/2008 and 28/02/2008. This represented a “trauma week” which is how the consultant rota is organised in our trust. We then compared this with the throughput in our elective unit for the same calendar period. No surgeons were on leave this week and no theatre sessions were cancelled other than the on call trauma consultant’s elective operating sessions. Our trust is a busy district general hospital with over 500 beds and approximately 55,000 emergency attendances per year. The orthopaedic directorate is staffed by ten full time consultants and serves a population of 315,000 patients.

All patient details were recorded prospectively and followed until the end of their inpatient episode. Case notes were then reviewed with the coding department and ICD-10 and OPCS-4 codes were generated. Their length of stay and other required variables were reviewed in order to generate the correct HRG code. Once the analysis was complete income for the trauma and elective groups were calculated.

Results:

Trauma:

48 patients were admitted (22 male) of which 36 required operative intervention. This utilised 14 theatre sessions. Mean age was 53.75 years (range: 7-93, median: 59). Median stay was 4 days with a mean of 13.3. The median and mean trim points (expected duration of stay before extra charges incurred by PCT) were 14.5 and 26.7 days respectively. Other consultants operated on 6 patients. This was either due to expertise in a specific area or space on an elective list utilised to reduce backlog. The income generated by these cases is included in the trauma total due to them being acute trauma interventions rather than elective cases. These results are summarised in tables 1 and 2.

Table 1: Demographic & Income Data of Trauma and Elective Patients

Table 2: Income by Anatomic Region

Of the 48 patients admitted 12 required no operative intervention. These cases were general ‘run of the mill’ admissions such as soft tissue infections for intravenous antibiotics, undisplaced fractures where home circumstances obstructed discharge, soft tissue injuries for further investigation and back pain. These will not be discussed further but the income generated (£31,127) does go towards the total. The median stay was 2 days with a mean stay 8.5 days (range: 1 – 47). This reflects the broad comorbidities and social circumstances of this subset.

The group requiring operative intervention included hip fractures (11 patients). Of these, seven required dynamic hip screw fixation but were deemed “complex” due to their comorbidities and therefore attracted the higher tariff rate (£6685). One displaced intracapsular fracture required total hip replacement, attracting a tariff of £7261. One patient required revision from a dynamic hip screw to an intramedullary device and then revision to a total hip arthroplasty. The tariff price was £19,479. The remaining fractured neck of femur patients attracted between £4379 and £6711 dependent on operative procedure. The median stay was 26 days (mean: 14, range 9 – 107). One patient required closed manipulation of a dislocated total hip replacement attracting a tariff price of £1034 and an inpatient stay of one day. In addition one acetabular fracture was sustained requiring open reduction and internal fixation. It attracted a tariff price of £4262 and an inpatient stay of seventeen days.

One patient required open reduction and internal fixation of a patella fracture attracting a tariff of £2405 and was an inpatient for 10 days. Another patient with septic arthritis required two arthroscopic knee washouts, attracting a tariff of £5941 and was an inpatient for 26 days.

Seven ankle fractures were admitted requiring operative intervention, all of these attracted a tariff of £2405 except one, which attracted £4262 due to co morbidity and complexity of injury. The median stay in this group was six days (mean: 4.9, range: 2-7).

Thirteen patients sustained hand and wrist injuries requiring operative intervention. Of these there were two tendon repairs, two abscesses drained and one digital terminalisation. Five wrist fractures required either manipulation and plaster application, closed reduction and Kirschner wiring or open reduction and internal fixation by means of a volar plate. Three fractures of the base of the thumb were manipulated and percutaneously K-wired. These patients attracted a tariff of between £1048 and £3227. Median stay was one day (mean: 1.36, range: 1 – 3). Three of these cases were managed by our hand surgeon on a trauma list.

One patient admitted with cauda equina syndrome required microdiscectomy attracting a tariff of £1271 and was an inpatient for one day. This was performed by one of our spinal surgeons on a trauma list.

Elective:

71 procedures were performed (36 female). This utilised 22 theatre sessions. Mean age was 49.51 years, (11 – 87 median: 47). Mean stay was 2.3 days. The median and mean trimpoints were 2 and 6.35 days respectively. Cases were divided by anatomical region. A table of income for both trauma and elective patients by anatomical region is included (Table 2).

Twelve patients had hip procedures performed. These included hip injections (n=2, tariff £615), sciatic nerve exploration (n=1, tariff £1217), cemented total hip arthroplasty (n=2, tariff £4304), uncemented total hip arthroplasty (n=1, £5305), resurfacing hip arthroplasty (n=5, £4023) and revision hip arthroplasty (n=1, £7185).

Twelve patients had knee procedures performed. These consisted of total knee replacements (n=3, tariff £5613), unicompartmental knee replacements (n=4, £5613), one anterior cruciate ligament reconstruction (£1863), knee arthroscopies (n=2, tariff £1063), one removal of metal work (tariff £1063) and one scar revision (tariff £1091).

Four patients had foot and ankle procedures performed and these all attracted £1217 tariff price. They consisted of one ganglion excision, one hallux valgus correction, one excision of Morton’s neuroma and one ankle arthroscopy.

Nine patients had upper limb procedures performed. These comprised carpal tunnel decompression (n =1 £1217), radial head excision (n=1 £1217), shoulder stabilisations (n=3 £1217), subacromial decompression (n=1 £1217), acromiclavicular joint excision (n=1 £1063), diagnostic shoulder arthroscopy (n=1 £1217) and arthroscopic cuff repair (n=1 £1887).

34 patients had spinal procedures performed. Inpatient stay ranged from 0 to 5 days with trimpoints of 1 – 13 days. These ranged from nerve root injections (n=23, tariff £522), discography (n=3, tariff £615), microdiscectomy and interspinous distraction (n=2, tariff £3192), decompression, fusions and instrumentation (n= 5, tariff £4252 - £5140), and kyphoplasty (n=1, tariff negotiated: no HRG code. Income £1506). Total income for the spinal group was £44,887.

It can be seen from the data that a wide range of trauma and elective surgery was performed and that the elective group was admittedly younger and had a shorter hospital stay (Table 1). Our unit has the benefit of two spinal surgeons who operate a local and tertiary practice, which changes the demographic of our cohort slightly; other units may not have this factor adjusting their income.

The tariff income for the elective group was £150,318, which was lower than that for the trauma group of £171,941.

Discussion:

This paper is, as far as we are aware the first to compare elective and trauma orthopaedic throughput in a busy district general hospital. It would be bold not to draw attention to our studies limitations. We analysed only one week in the financial year and we accept that seasonal variation may occur. The weather for the week in question involved no snow or ice and was warmer than average for this time of year (5.2°C)¹⁰. We do not feel that severe weather influenced our admissions. Previous studies have assessed the effect of seasonal variation on admissions rate. One was in a winter sports resort in Switzerland and unsurprisingly showed a positive correlation between season and fracture incidence¹¹. Another study based in Tasmania showed no variation in either vitamin D levels or incidence of femoral neck fracture¹². This goes against the findings of a study based at three latitudes, which showed a high seasonal peak in Scotland, Hong Kong and New ZealandOur locality has a temperate climate with no local winter sports resorts; our experience of seasonal variation is minor.

Miscoding and therefore error in calculations may have occurred; as both the authors and experienced coders reviewed the casenotes the likelihood of this is limited.

Our most important finding was that the mean income per trauma patient (£3658.32) was higher than that for an elective patient (£2045.13) and was statistically significant (p=0.001). The HRG code and income generated represents the money actually received by the hospital from the primary care trust. We openly admit that trauma patients represent a larger burden for the hospital. They have a tendency to be older, have complex co-morbidity and have increased length of stay. They are therefore more costly than elective patients. One study performed in a large university hospital calculated the mean cost for a hip fracture to be £8978.56 (range £3450 - £72,564), this rose to £25,940.44 if there was a superficial wound infection (range £4387 - £93,976) and £34,903 if there was a deep infection (range £9408 - £93,976)¹⁴.

Although actual income from the PCT was higher the trauma group will have been loss making on account of the hip fracture group. Whilst this is hard to quantify it seems likely given the calculations portrayed in the Nottingham study of 3686 patientsInpatient costs for the trauma group ignoring theatre costs amount to approximately £204,000. This exposes a lack of appreciation of this group’s requirements in comparison with fit elective hip patients and probably inequality in trauma coding for these patients.

Our study has not tackled implant costs partly due to the fact that inpatient costs have significantly dwarfed these but also due to the fact that we consider these a relatively fixed overhead, costs being determined by local bulk purchase agreements. The consequence on overall study outcome would be minimal given that trauma implants are several orders of magnitude cheaper than elective joint prostheses.

It became apparent to us during the course of our study that trauma can be under resourced when compared with elective care. The background team currently provided for trauma patients include the on call medical team (Consultant Orthopaedic Surgeon, Specialist Registrar and Senior House officer). In addition there are ward nursing staff, anaesthetist, theatre staff, occupational therapists and physiotherapists. On the elective side there are 4 waiting list clerks, 3 surgical assistants, 3 preoperative clinic sisters as well as reception staff and the background medical team (anaesthetist, consultant orthopaedic surgeon, specialist registrar and senior house officer). In the elective setting the aim is identification and optimisation of comorbidities pre-operatively and discharge planning to ensure throughput and turnover of patients. We admit that pre admission screening is not applicable to trauma but faster throughput could ensure improved efficiency and reduced duration of stay.

Our elective patients have a 30-bed ward with an additional 8-bed day case unit; the trauma ward has 24 inpatient beds. The elective unit has 7 registered nurses and 4 health care assistants; on the trauma ward this figure is 4 and 3 respectively. Our elective patients have 2.5 full time equivalent physiotherapists whilst our trauma patients have 1.5.

This situation is probably not dissimilar to the situation in many units elsewhere in the country. This work has shown that trauma income is higher than that for elective work and from this we can infer that if resources were directed accordingly then length of stay could be reduced and profit could be a possibility. A recent paper using hospital episode statistics (HESS) data has shown that length of stay fell quickly once payment by results was implemented¹⁵. What was unclear was whether this represented a real change in efficiencies or simply a change in data manipulation by trusts. HESS data has repeatedly been noted to be inaccurate with a range from 10 to 98% dependent on region and disease group.^16-17. In a 2006 statement by the then Health Minister Mr. A Burnham it was quoted that £88m pounds was being wasted from 390,000 extra unnecessary bed days¹⁸. This was based on the cost of an elective bed being £225 per day with acute beds being significantly more (approximately £320 in one study)The total stay for 66 elective patients was 118 days whereas that for 48 trauma patients was 637 days. Several outliers hugely increased the figure for trauma. Ten trauma patients represented 464 days of inpatient care. If the inpatient stay was reduced by one day for fractured neck of femur patients alone, this amounts to 500 less days per year and approximately £160,000 per year reduction in overhead costs for the trust.

One study in the USA assessed the use of a caseworker to expedite discharge for elderly patients with hip fractures¹⁹. The study did not utilise extra physiotherapy and occupational therapy support. Findings were increased theatre, anaesthetic and blood product costs in elderly patients. Increasing age did not correlate with length of stay, cost of stay or income for the hospital. They found that a case manager did reduce the average stay but did not reduce the overall cost. The NHS would do well to note these findings - in many trusts patient flow practitioners are being employed to try and expedite discharge and increase patient turnover. We feel that this money could be channelled into rehabilitation services to effect prompt rehabilitation and discharge.

One final issue is the variation in income between secondary and tertiary centres for certain injuries. One acetabular fracture underwent fixation generating £4262. If this had been referred to a tertiary centre a supplementary specialised service code would have been applicable generating more income (up to 70% in some cases) when intervention was identical. We agree that certain injuries require tertiary treatment by a team with high volume experience and specialised skills. There is an income chasm between the income generated between secondary and tertiary centres for the same injury, which seems perverse.

Overall trauma income was higher than elective income, but still ran at a loss. This was on account of the length of stay of the hip fracture patients and current coding underestimating their true cost to the trust. There is a disparity between rehabilitation services provided for trauma and elective patients, which needs to be addressed to improve efficiency.

The Care Programme Approach (CPA) was introduced in England in 1993 to co-ordinate the care of patients with mental health disorders.¹ Its aim was to ensure that there was a full assessment of the patient’s needs, that a care co-ordinator would see that the care was delivered, regular checks would be carried out to review progress, there would be collaboration between health and social services, and that patients (or the term used to ‘demedicalise’ them in psychosocial Newspeak ²  namely, ‘service users’) and carers (they also use the service) would have a greater say in the written management plan. Targets were set.

What has happened since? Prior to this I recall that most psychiatrists carried out full assessment needs, regular checks reviewed progress (outpatients), social services were involved when necessary, and  patients and their families were nearly always involved in the discussion of after-care, when appropriate. Despite the condescending manner in which patients and carers were treated by the hierarchy, i.e. they would not understand the difference between social services management and other after-care, it was always quite clear to doctors that patients had no difficulty with the concepts of medical intervention (investigations, diagnosis, treatment), psychological therapies, and social help (housing, work, family, finances). 

Rather than simplifying the process we now have two tiers of CPA, namely, standard and enhanced. Where the patient has ‘complex needs’ or is a ‘complicated case’ then you are in the enhanced bracket. For the rest – back to the General Practitioner (GP)! Not enough resources apparently. Not ill enough more likely. Remember – you have to have a severe and enduring mental health disorder – nothing else counts. Nowadays the GP is expected to be a specialist in mental health and run a risk assessment on every ‘psychiatric’ patient. The GP is frowned upon by the ‘experts in living’ should he/she for example, dare refer a mild or moderately (yes - those descriptions again!) ill patient to the Mental Health Services. Because there is no bottomless pit of money, the scenario was changed in 2008 so that those receiving only standard CPA were no longer entitled to it. However, not to appear callous and indifferent to the plight of those suffering from ‘less severe’ mental health problems, the usual lip service was paid to patients, assuring them that they should be respected and supported, and that their carers be also recognised as having ‘needs’. All the buzz words were put in place again – integrated care pathways, working together, reviews about the reviews, good practice, better training, and so forth. Now there is the Supervised Community Treatment Order, (whether you like it or not) and those subject to the new ‘order’ will be entitled to the ‘new’ CPA. Wonderful in theory.

So what happens to a patient who is not on CPA? We are informed that such patients should still be open to secondary mental health services, should continue to receive clinical support, that reviews should take place regularly, and a social assessment should be available under the new guidance to local authorities FACS (Fair Access to Care Services), readily available on the Internet. The truth of the matter is that only those patients on enhanced CPA will receive immediate support, the rest will have to jump through the usual hurdles to prove they have a severe, enduring mental illness (enduring is not enough) in order to gain access to NHS ‘support’ facilities. Some patients are seen as more deserving than others, for example, those admitted to hospital under the Mental Health Act (voluntary admission may count against you), current or potential risk (theoretically, any patient with a mental health disorder, which seems to defeat the purpose of the exercise) or the presence of a dual diagnosis (depression with alcoholism, or is it the other way round?). Anyway, if in doubt, the patient is entitled to a formal reassessment CPA and may be admitted to the ‘new’ CPA list. If all fails, the patient (remember, one with severe, enduring mental health symptoms) may make a complaint to the local authority or even hire a lawyer.

What is the true state of affairs? To begin with, many patients have enduring mental health problems which are not severe, are not life-threatening, and despite the hardship and drudgery endured, manage to trundle through work, relationships, and family life. Years of talking therapies or psychotropic medication, indeed both, may have only taken the edge off their symptoms. Often symptoms resurge and require alterations or adjustments in medication; sometimes a different psychological approach needs to be considered. Such patients are best left to the fountain of all wisdom, the GP, so it seems. Rather akin to telling the GP to treat for example, a ‘minor’ cardiac problem (say, palpitations) because the ‘specialist unit’ only deals with severe arrhythmias, severe pain, severe disability, ‘severe everything’. It is unfair to expect GPs to make informed decisions concerning psychotropic medication (no more than they should about adjusting chemotherapy drugs) and most would be familiar only with specific therapies such as Cognitive Behavioural Therapy (CBT) or Anger Management, where appropriate. The type of patients  described here comprise the majority of those seen in outpatients, yet there is now a growing trend to discharge such patients back to the GP, because he/she is not ‘care co-ordinated’ on enhanced CPA. The burden is on the GP. It does not seem to have registered with politicians or management (doctors included) that chronic schizophrenia is not the same as chronic gastro-oesophageal reflux.

The trend now is for the setting up of Community Clinics (the patient does not necessarily get to see a doctor) where ‘all the other psychiatric problems’ are dealt with. The traditional psychiatric outpatient department is to be abolished, unless of course, GPs do something about this torrid state of affairs now. It could only happen in Psychiatry which seems to me a specialty doomed to oblivion. Family doctors are becoming increasingly irritated by a system or discipline (Psychiatry especially) which seems to ignore their concerns and is more preoccupied with targets (nothing has changed) and outcomes (back to the GP). Even referrals from GPs, who want a medical opinion, are filtered in order to weed out those not worthy to enter the hallowed walls of the Mental Health Institution. Those patients who ‘know the system’ or who are vociferous and make complaints (‘I know my rights’) get to be seen by the Great and Good. Lesser mortals, usually those with serious mental illnesses, do not make any undue demands and are therefore often forgotten or fall by the wayside. A patient with bipolar disorder on lithium is discharged back to a GP who is unsure whether or not the medication needs ‘fine tuning’ at times, should be discontinued, or reinstated were compliance is a problem in one heading for a relapse. As a corollary of that, I am sure most hospital doctors would not know what the acronym ABVD means in the chemotherapy treatment of Hodgkin’s disease. Adjusting psychotropic medication is not quite the same as adjusting an antihypertension regime. Unfortunately, if the patient needs to be referred back into the system the whole Kafkaesque scenario begins again. 

A medical colleague once bemoaned to me that psychiatrists are totally out of touch with Medicine. Alas, it seems they are also now out of touch with their medical colleagues.

Many subjects with chronic Hepatitis C Virus (HCV) infection show persistently normal alanine aminotransferase (ALT) levels (PNALT),^1-4 and thus formerly defined as ‘healthy’ or ‘asymptomatic’ HCV carriers.¹ However, it is now clear that only a minority of these people show normal liver (15-20%).^5-7 Therefore,  ‘normal ALT’ does not always mean ‘healthy liver.’⁴

It is known that during the course of HCV infection ALT levels could fluctuate widely, with long periods of biochemical remission.^1-4Thus, at least two different subsets of HCV-PNALT carriers exist: patients with temporal ALT fluctuations, that could be within the normal range for several months, and true ‘biochemically silent’ carriers showing persistently normal ALT values.⁴It means that the observation period should not be shorter than 12 - 18 months, and ALT determinations should be performed every 2 - 3 months.^{4, 6}

Although liver damage is usually mild, ^{1, 2}the presence of more severe chronic hepatitis (CH) or cirrhosis has been reported despite consistently normal liver biochemistry.⁸Although some studies showed that HCV carriers with normal ALT have mild and rather stable disease, others reported a significant progression of fibrosis in approximately 20-30% of the patients with ALT normality.⁹The development of hepatocellular carcinoma (HCC) has been also described.¹⁰Sudden worsening of disease with ALT increase and histological deterioration has been reported after many years of follow-up.¹¹

Finally, HCV carriers with PNALT may suffer from extra-hepatic manifestations, sometimes more severe than the underlying liver disease: lymphoproliferative disorders, mixed cryoglobulinaemia, thyroid disorders, sicca syndrome, porphyria cutanea tarda, lichen planus, diabetes, chronic polyarthritis, etc.^{1, 2, 12}

Therefore, the possibility of progression to more severe liver damage despite persistently normal biochemistry, the risk of HCC, the possibility of extra-hepatic diseases, and economic considerations, suggest that HCV-infected persons with PNALT should not be excluded a priori from antiviral treatment.^{1, 2}

The earliest guidelines discouraged interferon (IFN) treatment in patients with PNALT because of the cost and side effects of therapy,^{1, 2} and of the low response rates to IFN monotherapy (<10-15%) with a risk of ALT flares in up to 50% of patients during treatment.⁹

The introduction of the combination of weekly subcutaneous pegylated-IFN (PEG-IFN) plus daily oral ribavirin (RBV) has led to response rates >50%, with a favourable risk-benefit ratio even in patients with slowly progressing disease.^{1, 2,  9} The first trial of PEG-IFN plus RBV found a sustained virological response (SVR) in 40% of HCV-1 carriers with PNALT treated for 48 weeks, and in 72% of HCV-2 and HCV-3 treated for 24 weeks.¹³The efficacy of antiviral treatment with PEG-IFN plus RBVwas subsequently confirmed in clinical practice.^{14, 15}

However, in everyday practice, management of carriers with PNALT may be paradoxically more difficult than that of patients with abnormal ALT levels. Indeed, it is not always so easy to ascertain in the single case whether it should be considered as healthy subject or true patient. Several topics to date remain unresolved: Should these ‘seemingly healthy’ people undergo routine liver biopsy? Is antiviral treatment justified in ‘asymptomatic’ subjects with persistently normal liver biochemistry? Is long-term follow-up needed in this setting, and how long it should last?²

Liver biopsy provides helpful information on liver damage, as it may reveal the presence of advanced fibrosis or cirrhosis. Without a biopsy, it is impossible to clinically distinguish true ‘healthy’ carriers from those with CH.⁴ On the other hand, it is difficult to recommend routine biopsy for all HCV-PNALT .⁴ The decision to perform a biopsy should be based on whether treatment is being considered, taking into account the estimated duration of infection, probability of disease progression, willingness to undergo a biopsy, motivation to be treated, and availability of non-invasive tools to assess liver fibrosis.¹² The recently developed transient elastography has improved our ability to non-invasively define the extent of fibrosis in HCV persons.⁵

Careful evaluation of parameters associated with disease progression is mandatory to assess the actual need for antiviral treatment.⁴ Indeed, it is really impossible to suggest antiviral therapy in all HCV carriers, as the costs would be exceedingly high, due to the high number of HCV patients with PNALT. Data from the literature indicate that the main factors of progression are male gender, advanced age, severe fibrosis, ALT flares, and steatosis.^1-2

Cost/benefit might be particularly favourable in:

• Young patients, having high rate of SVR (e.g. females, low viral load, HCV genotype non-1, etc).
• Middle age patients with ‘significant’ liver disease and/or co-factors of progression of liver damage, thus at risk of developing more severe liver disease.¹²

The age issue has a critical role for decision making. Younger patients have a higher chance of achieving SVR and tolerating therapy better; they a have longer life expectancy, are often well motivated, usually have minimal disease and fewer contraindications. Thus, in this group decision to treat should be based more on expected response and motivation than on the severity of liver disease.

On the contrary, older patients respond less well to therapy, are more likely to have significant liver disease and/or co-factors, could experience more side effects and may be less motivated. Thus, in this group decision to treat should be based on the severity of liver disease and on the possibility of SVR.

A recent Italian Expert Opinion Meeting suggested the following recommendations:¹²

1. HCV carriers with PNALT may receive antiviral treatment with PEG-IFN plus RBV using the same algorithms recommended for HCV patients with abnormal ALT.
2. Decision making should rely on individual characteristics such as HCV genotype, histology, age, potential disease progression, probability of eradication, patient motivation, desire for pregnancy, co-morbidities, co-factors, etc.
3. Treatment might be offered without liver biopsy in patients with a high likelihood of SVR (e.g. age <50 years + non-1 HCV genotype + low viral load), in the absence of co-factors of poor responsiveness.
4. Inpatients aged 50–65 years, and in those with a reduced likelihood of achieving a response, biopsy may be used to evaluate the need for therapy, with treatment being recommended only for patients with more severe fibrosis and higher possibility of SVR. Biopsy and therapy are not recommended in the elderly (>65-70 years).

In patients who are not candidates for antiviral treatment, follow-up may be continued, and ALT should be monitored every 4-6 months. Avoidance of alcohol and obesity may be strongly recommended.¹² It is not clear whether these subjects should be routinely offered anti-HBV vaccine, given the risk of disease progression in the case of HBV infection.¹² Antiviral treatment should be re-considered in the case of ALT flares, US abnormalities or platelet count decrease. Repeated measurements of serum HCV RNA to evaluate disease progression is not recommended.^{1, 9, 11, 12}.

Case report

A 78 year old man was admitted for re-fashioning of a prolapsing colostomy. Nine months previously he had undergone a juxtarenal aortic aneurysm repair complicated by ischaemic colitis, for which he had a sigmoid colectomy and a further laparotomy for refashioning of the stoma.

His past medical history consisted of anaemia, stable angina, superficial bladder cancer, Stage 4 chronic kidney disease, type 2 diabetes mellitus and osteoarthritis. He weighed 77 kg and his exercise tolerance was 100 yards, with the aid of a stick. His medications included doxazosin, quinine sulphate, perindopril, simvastatin, ferrous sulphate, isosorbide mononitrate and aspirin.

On examination, he was apyrexial with a blood pressure of 170/70 mm Hg, a heart rate of 65 bpm, a respiratory rate of 14 bpm and Sa0₂ of 98% on room air. Serum laboratory tests showed a prothrombin time of 13.4 sec (normal range 9.0 – 13.0 sec), haemoglobin 10.2 g/dL (13.0 – 16.7 g/dl), platelets 131 x10⁹/L (150 – 400 x10⁹/L), sodium 139 mmol/L, potassium 4.2 mmol/L, urea 15.7 mmol/L (2.5 – 7.0 mmol/L), creatinine 196 umol/L (50 – 130 umol/L) and eGFR 29 ml/min/1.73m² (>60ml/min/1.73m²).

His preoperative pulmonary function tests showed an FVC of 2.78L (93.8% predicted), a reduced FEV1 of 1.66L (75.2% predicted) and FEV/FVC of 59.87%. His ECG showed normal sinus rhythm. A CPEX test taken 12 months previously showed moderately reduced peak aerobic capacity, with a peak V0₂ of 11 ml/kg/min and an anaerobic threshold (AT) of 7 ml/kg/min.

In the anaesthetic room, the patient was connected to standard monitoring in accordance with AAGBI Guidelines and venous access secured with an 18 g biovalve cannula. Following pre-oxygenation, anaesthesia was induced using fentanyl 200 mcg, midazolam 2 mg, propofol 120 mg and atracurium 50 mg. Tracheal-intubation was achieved (grade 1 view) using an 8.0 mm cuffed endotracheal tube (lo-contour). A TAP block was administered following induction using ultrasound guidance (Sonosite ‘micromax’). A 50 mm insulated Stimi-Plex needle was used to inject a total of 40 ml levobupivacaine 0.375% bilaterally. Anaesthesia was maintained using a mixture of air, oxygen and sevoflurane (1.3 – 2.3 ETAA range). Intravenous (IV) paracetamol 1 g was given intraoperatively. The prolapsing colon was dissected through a circumstomal incision. A 10 cm length of colon was resected after ligation and division of the mesenteric vessels. The new end colostomy was fashioned with interrupted mucocutaneous sutures. Blood loss was minimal and there were no intraoperative complications. The duration of surgery was 1.5 hrs.

The patient spent 30 minutes in the postoperative recovery unit. He was awake, orientated and pain free throughout this period and clinical observations were stable. The patient remained pain-free on the ward and did not require any postoperative opioids. He was medically fit for discharge the following day.

Discussion

There are no previous case reports to our knowledge describing the use of TAP blocks in a patient with such poor CPEX testing preoperatively (AT = 7 ml/kg/min). CPEX testing has been shown to be an independent predictor of morbidity, mortality and length of hospital stay after major abdominal surgery.¹ The anaerobic threshold marks the onset of anaerobic metabolism as a result of inadequate oxygen delivery. It is not affected by patient effort and therefore provides a reliable patient specific measurement of functional capacity.² An AT of at least 11 ml/kg/min is recommended to safely undertake major surgery.² A combination of an AT of <11 ml/kg/min with ECG evidence of myocardial ischaemia is associated with high mortality and poor outcome. ³One study showed a mortality of 42% in those with ischaemic heart disease (IHD) and an AT <11 ml/kg/min, compared with just 4% in those with no IHD.⁴

Postoperative morbidity and mortality most often occurs in patients with pre-existing cardiorespiratory disease and a reduced functional capacity, due to their inability to withstand the additional physiological demands placed upon them by major surgery. Many of these patients develop features of organ hypoperfusion due to poor cardiorespiratory reserve.⁵

Our patient had an AT of 7 ml/kg/min and poor respiratory reserve (exercise tolerance of 100 yards, FEV/FVC 59.87% of predicted) but underwent uneventful intra-abdominal surgery with a good recovery and short length of hospital stay. Contributing factors may have been the anaesthetic technique used, as well as the surgical approach via a parastomal incision. Good intraoperative and postoperative control of cardiovascular parameters, temperature and pain are well known to reduce the surgical stress response and postoperative morbidity, and to improve postoperative outcome.⁶ Our patient was cardiovascularly stable throughout the perioperative period. His pain was well controlled with no opioid requirements due to the use of bilateral TAP blocks, and this probably contributed to his uneventful recovery, with no critical care requirement.

CPEX testing is not universally accepted as a useful preoperative assessment tool. In studies assessing it as a reliable predictor of outcome, there is heterogeneity in the degree of clinician blinding used. Blinding was used in some studies,¹ whilst in other instances, clinicians were aware of the CPEX results and changed their management accordingly. This obscures the true relationship between patient outcome and CPEX-derived measures of risk.⁷

TAP blocks were first described in 2001⁸ and have been shown to significantly reduce postoperative morphine consumption following abdominal surgery by up to 70%. They reduce pain scores at rest and during mobilisation in the early postoperative period (0-6 hours), and in the first 24 hours.⁹ The reduced requirement for morphine also leads to a reduction in postoperative nausea, vomiting and sedation.⁹ It may be possible that the ultrasound guided TAP block confers advantages in procedures with moderate surgical trauma to minimize pain and reduce opioid usage, thereby promoting faster recovery and discharge.⁸ TAP blocks were the chosen method of analgesia in our patient as they would elicit the least physiological disturbance, but would provide good postoperative analgesia, without opioid-related side effects. This was particularly beneficial, as his pre-existing renal impairment put him at increased risk of opiate toxicity. TAP blocks eliminate somatic pain relating to the surgical incision but do not treat visceral pain. However, our patient tolerated a 10 cm bowel resection with bilateral TAP blocks and intravenous paracetamol. A similar effect has been observed in other studies but the mechanisms behind it are unclear. One theory is that there is an analgesic effect due to high systemic levels of local anaesthetic.¹⁰

The use of CPEX testing to determine fitness for surgery should be interpreted with caution as newer anaesthetic and surgical techniques develop. Our patient had IHD and an AT which showed a significantly increased level of risk. However, a combination of regional anaesthesia and a cardio stable general anaesthetic with minimally invasive surgery, allowed a rapid and uneventful recovery with no opioid requirements and a short length of hospital stay.

Introduction:

On discharge from hospital, secondary care providers have a duty and obligation to communicate with primary care provides – particularly the general practitioner – to give information regarding the reasons for admission, results of investigations, procedures performed, treatment instigated and importantly follow-up management. Therefore the transition of information between secondary and primary care is vital for care management and hence patients’ safety.

This information is shared in the form of a ‘discharge summary’. It is the responsibility of the secondary care team to provide this. The level of detail given has been found to vary not just between different NHS trusts or hospital but also between different wards and individual doctors completing the discharge summary – this can create many problems as communication plays a pivotal role in patient care.

The information given in the discharge summary is all that a patients’ GP knows in regards to their hospital admission and management. A discharge summary is effectively a form of ‘handover’. A hospital physician may instruct the GP to do certain things in regards to follow-up; for example check blood results, review results of investigations arranged as outpatients or simply review the patient clinically. The more information that is transferred across from secondary to primary care the more awareness the GP has to what has happened and what needs to happen, which leads to better patient care.

A discharge summary can also be a valuable document for when a patient is admitted to hospital; if their notes are not available a past discharge summary will provide useful information (re. past medical history and drug history in particular) to the medical team who may have no prior knowledge of the patient, this is invaluable if it not possible to take a history from a patient and is also useful in directing investigations if a patient has been admitted with the same complaint(s). Of course this depends on the patient having a copy of the discharge summary with them on admission or the ability to access previous discharge summaries electronically.

Good documentation is vital in the healthcare setting. All documentation, no matter in what form, must be clear, accurate and legible. Any type of document is useless if it cannot be read. The GMC and Royal College of Physicians stress the importance of documentation^{1, 2}.

The importance of the discharge summary has been highlighted in the last few years. There has been a move from the traditional hand-written discharge summary – commonly referred to as the TTA (to take away) – to the use of computer software providing an electronic discharge summary (EDS). The latter not only provides more detail but also aims to deliver it to the primary care setting in a timelier manner; for example, in the future, once all EDSs are completed at Barking, Havering and Redbridge University Hospitals NHS Trust there are plans for them to be automatically emailed to a patients GP surgery – currently this scheme is being trailed at certain GP surgeries. This complies with the requirement and recommendations made to secondary care trusts to provide the GP with a discharge summary within 24hrs of a patients’ discharge from hospital – consequently reducing previous financial penalties when not achieved and thus being more cost efficient.

The advent of the EDS has impacted the daily working of the junior doctor, who is commonly, the individual on the secondary care team whose role it is produce the discharge summary. Previously with a TTA a patient could be discharged home without all the constituents on the form being completed and so a GP would be provided with an incomplete discharge summary. At BHR University Hospital NHS Trust in order to produce a finished EDS - and essentially discharge the patient - all constituent sections have to be completed before it can be electronically sent to pharmacy so that the patient sent home with their medications (the discharge summary acts as a prescription). Therefore producing an EDS is more time consuming in comparison to a TTA.  However an EDS does have advantages (see Table 1).

Table 1: Comparison of EDS and TTA

Any form of discharge summary is user dependent; what is written is determined by the individual doctor producing the document therefore there is no guarantee that they have documented everything that occurred during admission.  In the case of the TTA user dependence also refers to the legibility of the writing, the durability of the carbon copies produced, as well as the level of detail of the discharge summary produced.

In 2008 Newham University Hospital Trust introduced the EDS, the trust audited this process and found it to be successful³. 2010 saw the introduction of the EDS at BHR University Hospital NHS Trust. The EDS was piloted on Sunrise B ward of Queen’s Hospital, Romford. The purpose of this audit is to establish if the introduction of the EDS at BHR University Hospital NHS Trust has been successful. The audit aims to determine if the EDS method is superior to that of the traditional TTA – this will be achieved by comparing the completion rates for specific criteria of the discharge summary. This audit also aims to identify areas of improvement and recommendation for the EDS. 

Design and Method:

An opportunistic sample of 50 TTAs and 50 EDSs were selected from the patients admitted to Sunrise B (‘Care of the elderly’) ward, Queen’s Hospital, Romford in a two-month period (January to February 2011). Thus this is a retrospective audit. No exclusion criteria for selection of discharge summaries was set. For each discharge summary completion rates for the different fields of the discharge summary were recorded. Table 2 shows the criteria fields included in each type of discharge summary.

Table 2: Comparison of EDS and TTA criteria

The Royal College of Physicians have published their recommendations for the structure and content of the discharge summary. Section headings include

• GP details - name, address, practice code
• Patient details – surname, forename, date of birth, gender, NHS number, address, telephone number
• Admission details – method of admission, source of admission, hospital site, trust, date of, time of
• Discharge details – date of, time of, discharge destination, discharging consultant, specialty
• Clinical information – diagnosis at discharge, operations/procedures, reason for admission/presenting complaint, allergies, investigations and results, treatments, discharge medications, medication changes
• Advice, recommendations and future plan – hospital/GP/community
• Person completing summary – doctors name, grade, specialty, signature, date of completion⁴

This audit establishes which method of discharge summary is more compliant with these recommendations.

Data analysis was mainly descriptive. Data collected was tabulated and represented as percentages. Graphical representation of the data was performed using Microsoft Excel. Due to the nature of the study and data collected more sophisticated statistical analysis, such as that requiring the use of SPSS software, was not warranted.

Results:

Results demonstrate significant differences between the TTA and EDS completion rates for criteria of the discharge summary. Table 2 presents the data as percentages in a tabulated form. Compared to the TTA, the EDS had a higher rate of the following six criteria of the discharge summary documented; diagnosis, co-morbidities, investigations, drug history, discharge destination and instructions for GP.

Table 3: Summary table of data

•  Patient details and admission date.

The TTA had lower completion rates for these fields than the EDS. The EDS software automatically enters these fields therefore it is not possible for this criterion to be incomplete. The correct patient details ensure continuity of care and patient safety. If patient details – i.e. full name, date of birth, hospital number and address - are not present those with similar names could be mixed up.

Diagnosis.

The TTA performed poorly on documenting diagnosis. The EDS had a completion rate significantly higher than that of the TTA (EDS completion rate = 88%, TTA completion rate = 48%). Figure 1 represents these findings. The main objective of a discharge summary is to inform primary care of the diagnosis to enable healthcare management, therefore it is crucial and pivotal information, for it not to be included in the discharge summary is illogical.

Co-morbidities.

Neither TTAs nor EDSs documented co-morbidities well. However the EDS, yet again, outperformed the TTA. See Figure 1. Documenting co-morbidities has important repercussions for clinical coding and financial incentives (see below).

Investigations.

Coincidently, 62% of TTAs did not document investigations that the patient had had in contrast to 62% of EDSs that did. See Figure 1. There is no guarantee for either discharge method that all investigations are listed; it is dependent upon the doctor who is producing the discharge summary.

Figure 1: Graphical representation of data

Drug history.

As previously mentioned, EDS has to have a completed drug history before the patient can be discharged and hence they have to have a 100% completion rate for this criterion. TTAs only achieved a 64% completion rate as Table 3 demonstrates.

Review of case.

This is not a criteria field on the TTA document. Therefore 86% of TTAs provided no review. 88% of EDSs did provide a case review. Just fewer than 10% of EDSs were incomplete for this item.

Discharge date.

Like the admission date, a discharge date is automatically completed on an EDS thus the completion rate is 100%. However, this date is the date in which the EDS is completed and may not be the actual day the patient leaves hospital because sometimes the EDS is completed (and so the medications dispensed) the day prior to discharge or patient discharge may be delayed. The TTA achieved a 66% completion rate.

Discharge destination.

This is not a criterion present on the TTA and thus 100% of TTAs did not fulfil this requirement. EDSs had a 98% completion rate.

Follow-up arrangements.

The majority of EDSs documented the follow-up plans for a patient (88% in total, 70% specifically for GP follow-up). 46% of TTAs documented patient follow-up required, specifically 44% for hospital follow-up. 54% of TTAs documented no follow-up. In summary, 88% of EDSs documented follow-up in comparison to 46% of TTAs. These findings may be a limitation of the study i.e. patient selection rather than failings in documentation.

Instructions for GP and functional status.

Coincidently, 92% of TTAs did not document ‘instructions for GP’ in contrast to 92% of EDSs that did. ‘Instructions for GP’ is not a criterion on the TTA document.

Functional status.

‘Functional status’ is also not a criterion on the TTA document and so all TTAs were not complete for this. 64% of EDS had a completion rate for documenting ‘functional status’. Functional status indicates a patient’s mobility status, self-care abilities, hearing and sight impairment.

Discussion:

This audit has established that the EDS has a higher completion rate for criteria on the discharge summary, significantly so for documenting diagnosis, co-morbidities, investigations, drug history and instructions for the GP.

One major concern that has been highlighted in performing this audit is the documentation of co-morbidities. Due to variations in training many doctors are unaware of how and where to enter this information on the EDS – there is a specific window that opens on the software program to input this information. Junior doctors were documenting patients’ past medical history under the field of ‘diagnosis’. Co-morbidities should not be listed under ‘diagnosis’ - this infers a new diagnosis - as they are not the acute problem.

The coding of the diagnosis [the acute problem], in context of a patients co-morbidities, results in a condition specific ‘fee’ being paid to secondary care. For example the ‘fee’ received for a patient diagnosed with a respiratory tract infection is different for that when the patient is diagnosed with a respiratory tract infection on the background of dementia. Inaccuracies in diagnosis lead to incorrect coding and measures of incidence. Co-morbidity is ‘any condition which co-exists in conjunction with another disease’. It is a requirement of the discharge summary to document certain co-morbidities – as determined by the Clinical Coding Co-morbidity Working Group (CCCWG)⁵. Although the discharge summary is not the recommended source documents for use in clinical coding – patients medical notes are used instead – it can help direct and inform those responsible for clinical coding. In should be borne in mind that it is the treating clinicians’ responsibility to document co-morbidities relevant to the current admission. Accurate and correct clinical coding will result in financial gains. Clinical coding has more important purposes other than just financial; it allows the monitoring of health services, epidemiological research, NHS planning of provisions, as well as clinical audit and governance⁶.

The amount of information documented is user dependent; the level and amount of detail written is subjective.  For example there is no guarantee that all the investigations that a patient had are documented. One doctor may provide a whole paragraph to summaries [‘review of case’] whereas another may just write one sentence. Educating those whose task it is to complete the discharge summary about how vital and important it is, along with the role it serves in healthcare management, may influence the effort and time dedicated to producing an EDS. The principles of clear, complete and concise documentation should be applied to both the patients’ discharge summary and their medical notes.  

Other healthcare professionals should also contribute to producing the discharge summary, in particular occupational therapists and physiotherapists who are more aware of a patients ‘functional status’ than the doctors. More accurate completion of this item could be achieved with their input. 

At the moment with the EDS software system used at BHR University Hospital Trust once an EDS has been printed there is no means of changing any of the information. It cannot be re-accessed to document new or change existing details. Often an EDS will be finalized and so printed for a patient to be discharged home on that day for the discharge then to be delayed. The discharge date document on the EDS should be the actual date the patient is discharged from hospital. Therefore it should be possible to be able to re-access and change details on the EDS.

The results of this audit show that the EDS system used at BHR University Hospital Trust is better then the EDS system audited at Newham in 2008. The Newham audit did not focus on all the criteria fields of the discharge summary or compare with a hand-written discharge summary method, however there is place for comparison with the results of this audit.

Table 4: Comparison of results with findings of Newham audit

This audit has established that the EDS method provides a discharge summary more compliant with the Royal College of Physician’s recommendations on the structure and content of discharge summary in comparison to the TTA.

The EDS will inevitably replace the TTA in time. However it should be remembered that there is still a place for the TTA in clinical practice e.g. locums do not have passwords to access the software programme, if computers are not working, fail or are unavailable. At the end of the day, a discharge summary is better than no discharge summary.

Conclusion:

The findings of this audit show that the EDS is a far superior method of producing a discharge summary than the TTA. The EDS provides a more informative and detailed discharge summary, which is always legible. The discharge summary is often the only source of information a GP is given in regards to a hospital admission and therefore secondary care providers have an obligation to provide clear, complete and concise information.

This audit does highlight that there are areas for improvement and recommendation:

• The importance of a discharge summary should be highlighted to all individuals whose responsibility it is to complete them. This could promote better compliance at completing all items and completing them more thoroughly.
• EDS training should make users aware of the ‘co-morbidity’ section. Past medical history should not be listed under new diagnosis. This should be a compulsory part that has to be completed before an EDS can be finished.
• Occupational therapists and physiotherapists should be able to complete the ‘functional status’ criterion. This should be expanded to give more information and details to primary care providers.
• The documentation of certain co-morbidities (those determined by the CCCWG) should be done by ‘tick list’ selection therefore it will not rely upon the individual doctor to remember to document such co-morbidities. All the co-morbidities that should be documented could be listed and the user selects those that the patient has. This will improve the trusts performance in regards to the financial rewards linked to discharge summaries.
• The audit should be performed again in 12 months to access if EDS are maintaining high completion rates, to identify further improvement in completion rates and identify any further areas for improvement or recommendation.
• Discussion of both TTA and EDS could be a part of the regular weekly supervision of junior medical staff by their prospective consultants.
• A discharge summary should also be checked by nursing or clerical staff prior to letting the patient leave the ward to see if all components are completed.

Introduction

Thyrotoxic periodic paralysis (TPP) is an uncommon disorder characterised by simultaneous thyrotoxicosis, hypokalaemia, and paralysis that occurs primarily in males of South Asian descent.¹ Many affected patients do not have obvious symptoms and signs of hyperthyroidism and hence may be misdiagnosed or overlooked on presentation.² We hereby report a male patient who presented to us with weakness of all four limbs. The patient was evaluated and diagnosed to be having TPP.

Case History

A 30-year-old male patient, who was an agriculturist by profession, presented with weakness of all four limbs of one-day duration. The weakness first appeared in his lower limbs and then in the upper limbs. There were no sensory symptoms or bladder involvement. He was not a known hypertensive, diabetic or thyrotoxic patient. He was not on any medication for any significant illness.

On general physical examination, there was no pallor, icterus, cyanosis, clubbing, lymphadenopathy or pedal oedema. Multinodular goitre was noted on thyroid examination. There was no exopthalmos, lid lag, pretibial myxoedema or other signs of thyrotoxicosis.  Thyroid bruit was absent.  Pulse rate was 96/minute, blood pressure of 140/80mmHg, and respiratory rate 18/minute. On central nervous system examination, the higher mental functions and cranial nerve examination were within normal limits. Motor system examination showed the presence of flaccid quadriparesis with areflexia. Sensory system examination was within normal limits. Cardiovascular and respiratory system examination were normal.

Investigations revealed: haemoglobin (Hb) -13.1 gm%, total count (TC) - 11,400/cmm, platelet count - 49,000/cmm, random blood sugar (RBS) - 110mg/dl, blood urea - 29 mg/dl, serum creatinine - 0.8 mg/dl. Serum electrolyte profile showed sodium - 143 mEq/L, potassium - 2.2mEq/L, chloride - 112mEq/L. Serum calcium and magnesium levels were within normal limits. Electrocardiogram (ECG) was normal. Human Immunodeficiency Virus (HIV) ELISA was non reactive. Bone marrow biopsy and ultrasonography of abdomen were normal. Fine Needle Aspiration Cytology (FNAC) of thyroid showed features of hyperplastic colloid goitre. Ultrasonography of thyroid showed hyperechoic small nodules in both lobes as well as isthmus suggestive of multinodular goitre. Thyroid profile was: total T3 - 2.34 (normal: 0.60 - 1.81ng/ml), total T4 - 13.9 (normal: 4.5 - 10.9 mcg/dl), thyroid-stimulating hormone (TSH) - 0.01 (normal: 0.35 - 5.5IU/ml). Antithyroid antibodies and antiplatelet antibodies were negative. Nerve conduction study was normal. A final diagnosis of TPP with idiopathic thrombocytopenia was made.

The patient was administered 40mmol potassium chloride intravenously.  He was treated with tablet carbimazole 10mg three times a day and tablet propanolol 10mg twice a day. The patient’s weakness in all four limbs improved dramatically within an hour after potassium chloride administration. As he had persistent thrombocytopenia during his stay in hospital, he was commenced on tablet prednisolone (1mg/kg body weight). His platelet count normalized in one month after which the steroid dose was tapered and stopped.

Discussion

TPP is an uncommon disorder characterised by simultaneous thyrotoxicosis, hypokalaemia and paralysis that occurs primarily in males of South Asian descent. The overall incidence of TPP in Chinese and Japanese thyrotoxic patients is 1.8% and 1.9% respectively.^{3, 4} Sporadic cases have been reported in non-Asian populations such as Caucasians, Afro-Americans, American Indians and Hispanics. With population mobility and admixture, TPP is becoming more common in Western countries. Many affected patients are in the age group of 20 - 40 years and do not have obvious symptoms and signs of hyperthyroidism.⁵ The attack is characterised by recurrent, transient episodes of muscle weakness that range from mild weakness to complete flaccid paralysis. The proximal muscles are affected more severely than distal muscles.  Attacks usually first involve the lower limbs, and progress to the girdle muscles and subsequently the upper limbs. Sensory function is not affected. Although patients can present with quadriparesis that resembles Guillain-Barre Syndrome or transverse myelitis, the bladder and bowel functions are never affected. Patient may experience recurrent episodes of weakness that last from a few hours up to 72 hours with complete recovery between the attacks. In the majority of patients, deep tendon jerks are markedly diminished or absent although some patients may have normal jerks.

Patients with TPP usually experience the attacks a few hours after a heavy meal or in the early morning hours upon waking. More than two-thirds present to the emergency department between 2100 and 0900 hours; hence it was initially described as nocturnal palsy or night palsy.⁶ It has been shown that plasma glucose and insulin responses to meals are markedly higher in the evening than in the morning in control subjects. Such a phenomenon suggests a possible mechanism for the nocturnal preponderance of TPP. Another explanation could be the circadian rhythmicity of many hormones reaching their peak levels during sleep. Hypokalaemia is considered to be the most consistent electrolyte abnormality in TPP and a hallmark of the syndrome along with hyperthyroidism. It has been demonstrated that hypokalaemia is a result of potassium shift into cells and that it is not caused by total body potassium depletion.⁷ Patients with thyrotoxic periodic paralysis have an underlying predisposition for activation of Na+/K+-ATPase activity either directly by thyroid hormones or indirectly via adrenergic stimulation, insulin or exercise. Increased Na+-K+ ATPase activity is postulated to contribute to hypokalaemia.⁸

The majority of cases of hyperthyroidism associated with thyrotoxic periodic paralysis are due to Graves disease although other conditions including thyroiditis, toxic multinodular goitre, toxic adenoma, TSH secreting pituitary tumour, ingestion of T4 and inadvertent iodine excess have also been implicated.⁹ Assaying of thyroid function in patients with hypokalaemic paralysis distinguishes thyrotoxic periodic paralysis from other forms of hypokalaemic periodic paralysis. Thyrotoxic periodic paralysis occurs only in the presence of hyperthyroidism and is abolished when thyroid hormones are normalised.

Immediate therapy with potassium supplementation and beta-adrenergic blockers can prevent serious cardiopulmonary complications and may hasten recovery of periodic paralysis.¹⁰ Potassium chloride is given intravenously and/or orally. Regular potassium supplementation as prophylaxis against further paralysis when the patient has normal serum potassium level is ineffective. Effective control of hyperthyroidism is indicated to prevent recurrence of paralysis.

Conclusion

To conclude, although the association of thyrotoxicosis and periodic paralysis has been well known, TPP is often not recognised when first seen because of lack of familiarity with the disorder and partly because of the subtleness of thyrotoxicosis. When a young male of South Asian descent is initially seen with severe lower limb weakness or paralysis, TPP should be considered in the differential diagnosis and investigated for its presence since it is a curable disorder that resolves when euthyroid state is achieved.

An 80-year old lady was referred to a gastroenterology clinic in August 2009 with deranged liver function tests; alkaline phosphatase 180 IU/L (35-120), alanine transferase 147 IU/L (<40), gamma glutamyl transferase 384 IU/L (<45) and globulins 45 g/L (20-35).  She had initially presented to her general practitioner with symptoms of lethargy and malaise four months previously. She denied any symptoms of obstructive jaundice and there were no risk factors for hepatitis; she seldom consumed alcohol. 

Past medical history included osteoarthritis, migraines and recurrent urinary tract infections; these had been investigated by urology and the patient had undergone cystoscopy and urethral dilatation in September 2003; despite this she continued to experience urinary tract infections and was therefore commenced on prophylactic nitrofurantion by her General Practitioner with approval by the Urologist.  This was initially commenced at 50mg at night.  This regime was continued for approximately three years however during this time she had a further three treatment courses of nitrofurantoin.  In October 2005 her prophylactic dose was therefore increased to 100mg at night. Other medication included lansoprazole 30mg daily, pizotifen 500 micrograms at night, metoprolol 100mg twice daily, simvastatin 10mg at night, senna 15mg at night and furosemide 40mg daily.

On examination there was evidence of palmar erythema and Dupuytren’s contractures but no other stigmata of chronic liver disease.  The liver was tender and palpable 4 cm below the costal margin. A liver ultrasound was performed which was normal.  Liver screen and autoimmune profile are shown in table 1; notably a positive nuclear antibody was found (1 in 1280 IgG) with Hep 2 cell staining showing a homogenous (ANA) pattern at 1:320 IgG, and a nuclear lamin pattern at 1:1280 IgG;.  Due to the positive ANA and raised globulins a suspected diagnosis of nitrofurantoin-induced autoimmune hepatitis was made and a liver biopsy performed.

Table 1: liver screen and autoimmune profile
 

Figure 1a. Liver biopsy showing portal-based interface hepatitis
 

Figure 1b. Liver biopsy showing portal-based interface hepatitis
 

Figure 2. Serial LFTs over time

Liver biopsy (figure 1) indicated a moderate hepatitis which was mainly portal based with multifocal interface hepatitis; these morphological appearances were consistent with those of an autoimmune hepatitis. The patient was advised to immediately stop nitrofurantoin and was commenced on prednisolone 30mg which caused a rapid improvement in LFTs (figure 2). This improvement was maintained following a step-wise reduction in steroid dose and prednisolone was discontinued after eight months of treatment. LFTs are currently normal one month following cessation of steroids

Discussion

This case raises two points of discussion.   The first is whether the long term use of nitrofurantoin as prophylaxis for urinary tract infections is appropriate and based on solid evidence. Nitrofurantoin has many side effects and is well documented to cause liver derangement^1,2,3. The patient described in this case had been taking nitrofurantoin for seven years and had received a large cumulative dose, on the basis that this was effective prophylaxis. The continuous, long term use of antibiotics as prophylaxis for urinary tract infections is debatable.  Madersbacher et al⁴ recommend the use of prophylactic antibiotics  but only after or alongside additional measures including behavioural change, the use of topical oestrogens and the use of alternative therapies; this view is supported by the European Association of Urology⁵.A Cochrane Review⁶  in 2004 found that antibiotic use did decrease the number of urinary tract infections compared to placebo but only for the duration of treatment; antibiotics  do not alter the natural history of the underlying condition⁷. There is no clear evidence for duration of treatment and any trials have only been continued for six or twelve months⁶.  It has been noted that all antibiotics had a worse adverse event profile compared to placebo. There was no consensus as to which antibiotic should be used although nitrofurantoin has been associated with a greater withdrawal rate⁶. One study⁸ comparing nitrofurantoin and trimethoprim revealed no significant difference in recurrence rates or side effects between the two antibiotics, although this involved a lower dose of nitrofurantoin than was used in this case, and a treatment duration of just 6 months. We would argue that due to the side effect profile of nitrofurantoin and the evidence base available, it is not appropriate to continue it for a duration beyond 6 months.

The second discussion point is whether nitrofurantoin was actually the cause for liver derangement in this case. As documented in a recent review article on the diagnosis of drug-induced liver injury, establishing with any certainty whether liver injury is drug induced can be very difficult³.   The key issues are whether there is a temporal relationship between the drug and the onset of liver injury, and whether other causes have been excluded.  In this case the patient had negative viral serology and a normal ferritin and caeruloplasmin but her positive autoantibodies raise the possibility of autoimmune hepatitis.  Guidelines from the American Association for Liver Diseases⁹ suggests that the diagnosis of autoimmune hepatitis should be made on the following criteria

• laboratory abnormalities (serum AST or ALT,  and increased serum total IgG or gamma-globulins)
• positive serological markers including ANA,SMA, anti-LKM1 or anti- LC1
• histological changes consistent with autoimmune hepatitis i.e. interface hepatitis

This case meets these above criteria for autoimmune hepatitis however the presence of nitrofurantoin does confound the issue. Other case reports¹⁰  have reported nitrofurantoin to have caused autoimmune hepatitis based on the relationship between the timing of the drug and the onset of biochemical abnormalities.  Bjornsson et al¹¹ performed a comparative study of patients with autoimmune hepatitis and found drugs, particularly nitrofurantoin and minocycline were causally implicated in 9% of cases.  When they compared the two groups no significant differences were found in the diagnostic parameters of biochemical, serological and histological abnormalities.  In fact the only difference was that no drug-induced cases relapsed on withdrawal of steroids whereas nearly two third of those with non-drug-induced hepatitis relapsed. Bjornsson et al therefore argue in favour of autoimmune immune hepatitis being induced by drugs such as nitrofurantoin; rather than particular drugs simply unmasking sporadic cases based on these management differences. 

The patient in this case so far has shown no signs of relapse following steroid withdrawal.  We believe that this case does represent one of nitrofurantoin-induced autoimmune hepatitis. In view of the above we would urge readers to consider their use of nitrofurantoin for recurrent urinary-tract infection prophylaxis.

Doris-Eva Bamiou is a Department of Health HEFCE funded Senior Lecturer at the UCL Ear Institute, and Consultant in Audiovestibular Medicine at the National Hospital for Neurology and Neurosurgery. She is also  Honorary Consultant at the RNTNE Hospital and Great Ormond Street Hospital. She sees both adults, with vertigo, hearing problems or auditory processing disorders, and children with auditory processing disorders and complex communication needs in her clinics. She works in an academic, multidisciplinary environment.

After completing specialty training in ENT in Greece, Ms Bamiou trained in Audiological Medicine in the UK. During her training, she spent a three-month fellowship in Professor Musiek’s department in the States (on a stipendium from Professor Musiek and a grant from the TWJ foundation), where she trained in the diagnosis and management of patients with auditory processing disorders. Her PhD degree is onauditory processing in patients with structural brain lesions.

She is Director of the MSc in Audiovestibular Medicine at UCL. In addition, she has been Director and Organiser of the Current Trends in Auditory Processing Disorders instructional courses for the past several years. She is immediate past Secretaryof the British Society of Audiology (BSA), and Chair of the Auditory Processing Disorders Special Interest Group of the same Society. She is adviser in Audiology to the JLO, and in the Editorial Board of the Audiological Medicine journal.

She has a keen interest in research. Interests include the aetiology of hearing loss, auditory processing disorders in the presence of other neurological conditions as well as in the normal population, auditory neuropathy, vestibular rehabilitation and overlap between psychiatric and vestibular disorders.

How long have you been working in your speciality?

I first became interested as an ENT trainee in Greece, in 1993. At the time I was at a paediatric hospital, and we did a lot of paediatric testing (distraction and ABR). In 1994 I moved to an adult hospital, where I came across and learned to test and manage adult patients with vertigo and hearing loss.

Which aspect of your work do you find most satisfying?

Solving clinical problems, teaching postgraduate students, designing research projects and interpreting research results give me equal satisfaction – I enjoy equally the patient/doctor or student/teacher interaction and the intellectual challenges.

What achievements are you most proud of in your medical career?

I set up the first adult clinic for patients with auditory processing disorders at the National Hospital for Neurology, and the first multidisciplinary clinic in this field, again at the same hospital.

Which part of your job do you enjoy the least?

Administration and form filling exercises.

What are your views about the current status of medical training in your country and what do you think needs to change?

I wonder whether trainees get enough proper training in their very early days on and whether the length of the training is sufficient for them to be able to function independently by the end of their training.

How would you encourage more medical students into entering your speciality?

We do Audiovestibular Medicine Taster days, and we encourage them to come and “shadow” us to see what it is really like.

What qualities do you think a good trainee should possess?

He/she should be kind, hard working, highly motivated to learn and able to develop independent thinking.

What is the most important advice you could offer to a new trainee?

It may be hard work training as a Doctor, but it’s all worth it!

What qualities do you think a good trainer should possess?

Amongst many other things, empathy, and the ability to teach each trainee at their own level.

Do you think doctors are over-regulated compared with other professions?

Not more than is required.

Is there any aspect of current health policies in your country that are de-professionalising doctors? If yes what shouldbe done to counter this trend?

I think it is difficult to reconcile managerial activities with a doctor’s role.

Which scientific paper/publication has influenced you the most?

Several. I tend to read a lot of papers for lectures etc so this changes every few weeks!

What single area of medical research in your speciality should be given priority?

I could not separate one more than others.

What is the most challenging area in your speciality that needs further development?

Rehabilitation (auditory and vestibular) of the patient with complex needs.

Which changes would substantially improve the quality of healthcare in your country?

More funding and more rationalized use of free NHS services, depending on the patient’s income.

Do you think doctors can make a valuable contribution to healthcare management?  If so how?

Yes, by working closely and by educating managers.

How has the political environment affected your work?

Not at all.

What are your interests outside of work?    

I read a lot of books of every kind, I go to the theatre and to art exhibitions.

If you were not a doctor, what would you do?

This will sound very boring. I would still like to be a doctor!

Warfarin is the most commonly used oral anticoagulant and has established efficacy for more than 50 years for the prevention of thromboembolic events, but its use is limited by fear of bleeding, drug-drug and drug-food interactions, and routine monitoring of international normalized ratio (INR). In patients with atrial fibrillation (AF), warfarin prevents 64% of strokes in research studies but the real-world effectiveness drops to 35% because of various factors leading to its suboptimal use.¹ In October 2010 the United States (US) Food and Drug Administration (FDA) approved Pradaxa capsules (dabigatran etexilate) as the first new agent to prevent stroke and systemic emboli in patients with non-valvular AF. In this article we will discuss some of the evidence for and against the use of dabigatran.

In the RE-LY study² (Randomized Evaluation of Long-term Anticoagulant Therapy), high-dose dabigatran (150mg twice a day) was found to be superior to warfarin for the prevention of stroke and systemic emboli, required no routine INR monitoring, and had few food and drug interactions. James Freeman and colleagues,³ using data from the RE-LY trial, found that high-dose dabigatran (150mg twice a day) was the most efficacious and cost-effective strategy compared with adjusted-dose warfarin among adults older than 65 with AF.

Dabigatran has been shown to specifically and reversibly inhibit thrombin, the key enzyme in the coagulation cascade. Studies in healthy volunteers⁴ and in patients undergoing orthopaedic surgery have indicated that dabigatran has a predictable pharmacokinetic/pharmacodynamic profile, allowing for a fixed-dose regimen. Peak plasma concentrations of dabigatran are reached approximately two hours after oral administration in healthy volunteers, with no unexpected accumulation of drug concentrations upon multiple dosing. Excretion is predominantly via the renal route as unchanged drug. Dabigatran is not metabolized by cytochrome P450 isoenzymes. Though use of dabigatran for non-valvular AF and venous thromboembolism (VTE) is gaining practice,⁵ it remains far from being the standard of care. 

What are the concerns with use of dabigatran? In the RE-LY study the INR control was relatively poor (64% TTR (time in the therapeutic range)) but, probably more importantly, the relationship between events and individual’s INR control was not reported. The use of centre’s time in therapeutic range (cTTR) in the RE-LY study as a surrogate for INR control may not truly reflect TTRs for individual patients. Also in RE-LY study, randomization was stratified for centre and by the centre-based analyses, and the quality of oral anticoagulant services was the basis for the comparisons in this report. A subgroup analysis⁶ concluded that relative effectiveness of dabigatran versus warfarin was mainly seen at centres with poorer INR control. For example, Swedish centres had good TTR and the relative effectiveness and safety of dabigatran was virtually the same as with warfarin; thus, it is only the price difference that counts. It also highlights how local standards of care affect the benefits of use of new treatment alternatives and hence further limits the generalizability of any ‘overall average’ cost-effectiveness of dabigatran,  raising the question that if an intervention does not do more, why should a payer pay more for it? There are several other factors that could impact on the cost-effectiveness⁷ of dabigatran such as patient medication adherence, dosing frequency, and the potential effect of new efficient methods of warfarin management improving INR control by patient self-testing.

The other shortcomings of dabigatran include lack of antidotes when patients do bleed and lack of any alert to physicians that patients are not compliant with dabigatran (INR serves this purpose for warfarin). Additionally, in the RE-LY trial, dabigatran was used twice daily thus raising compliance issues compared to once daily warfarin (the rates of discontinuation of dabigatran were higher at 15% and 21% at one and two years, respectively); 11.3% reported dyspepsia (twice the rate of warfarin group); high rate of gastrointestinal bleed compared with warfarin; patients in the dabigatran cohort were at slightly higher risk of myocardial infarction (not sure how it will translate in real world practice); and contraindication of dabigatran in severe renal dysfunction raises some more questions about its use and cost effectiveness. In addition, the RE-LY trial excluded patients who had: contraindications to anticoagulation, severe heart-valve disorder, stroke within 14 days or severe stroke within six months before screening, a condition that increased risk of haemorrhage, creatinine clearance of less than 30ml per minute, active liver disease, and pregnancy.  Clinicians will need to use their judgement to weigh and balance the risk for bleeding with this new agent in a setting of an acute stroke versus the risk of having another ischaemic stroke in someone with AF if not given anti-coagulation therapy immediately. Safety and efficacy at extremes of body weight is not well established with current FDA approved doses of dabigatran either.

In summary dabigatran is a very exciting new agent with significant advantages over warfarin. However, in view of dabigatran’s higher non-adherence rate and greater risk of non-haemorrhagic side effects, patients already taking warfarin with excellent INR control have little to gain by switching to dabigatran.¹ Until more studies and post-marketing data become widely available, we should advocate tight INR control for which there is a wealth of evidence for benefits, and promote strategies to improve the management of therapy with warfarin.

Introduction

Sedation is frequently administered outside of the operating theatre by non-anaesthetic doctors to facilitate minor procedures.  This can be in both primary care including dental surgeries as well as in hospital departments such as radiology, endoscopy and the emergency department.  Clinical practice including medication and monitoring equipment available and the personnel involved, varies not only between hospitals and regions but also between departments.

In the emergency department sedation is often performed in a busy clinical setting by junior doctors.  This enables minor procedures to be carried out with subsequent discharge home reducing admission rates and the requirement for general anaesthesia.  Other advantages include less workload pressure on the anaesthetic team and a significant improvement in the patient experience.  Sedation is not without risk and significant morbidity and mortality is still associated with its use, particularly in the elderly and in combination with other medication^1,2.  Guidelines and protocols do exist to ensure safe practice but often it is only anaesthetic doctors who are aware of them^3-7.  A recent study by Fanning highlighted discrepancies in practice, skills and knowledge of doctors of various specialities and grades who administered sedation⁸.  Anecdotal reports from orthopaedic colleagues suggested the variability in competence of doctors with clear implications for patient safety.  We therefore sought to ascertain the current clinical practice, knowledge and prior training in sedation techniques of specialist registrars in orthopaedic and trauma surgery in our region.

Materials and Methods

A questionnaire based survey of 53 specialist registrars in orthopaedic and trauma surgery in the neighbouring Severn and South Wales regions was carried out.  The questionnaire was modified from that developed by Fanning⁸ and circulated for completion at regional teaching sessions in Swansea and Bristol (Appendix 1).  Each respondent had 15 minutes to complete the questionnaire based on their own experience, practice and knowledge. Respondents were not allowed to confer and full confidentiality was assured.  The questionnaire was split into several sections that ascertained the respondents’ clinical practice including the procedures that sedation was used for, prior training, awareness of protocols and safety issues.  Knowledge of the basic pharmacology of commonly used sedative agents was also tested.  The final section asked respondents whether they had ever encountered any adverse events, the nature of the adverse event and whether assistance was required from the anaesthetic department.      

Results

Orthopaedic specialist registrars (post basic surgical training) who were in higher surgical training completed 53 questionnaires.  Sedation was performed in the emergency department by all respondents for manipulating fractures, reducing dislocated joints and for applying traction.  Twenty-four respondents (45%) had read the sedation protocol for their hospital/emergency department.  Thirteen respondents (25%) completed pre-sedation assessment forms, whilst only eleven (21%) completed the during-procedure monitoring data forms and twelve (23%) filled the after-procedure forms (Figure 1).  Twenty-eight (53%) respondents ensured that either they or an assistant provided the patient with discharge advice.

Figure 1The percentage of respondents who had read the departmental protocol, completed monitoring forms and given advice prior to discharge.

Table 1:  Sedative agents used.

Almost all (98%) respondents administered sedation in the presence of an assistant.  Forty-seven (89%) checked their medication with another healthcare professional.  All fifty-three respondents supplied patients with concurrent oxygen whilst fifty-two ensured that resuscitation equipment was available nearby.  In terms of specific training, forty-seven (89%) registrars had undergone Advanced Life Support training (ALS) but this qualification was only valid (within three years) for thirty-six (68%).  Sixteen registrars (30%) stated they had undergone formal training or teaching regarding sedation (Figure 2).  With regards to monitoring of patients, thirty-six (68%) respondents used pulse oximetry, fourteen (26%) used electrocardiogram (ECG) monitoring and twenty-eight (53%) measured blood pressure. 

Figure 2The proportion of respondents who had received training in administering sedation

Morphine and other opioids were the most commonly used sedative medication (44 responses), followed by midazolam (35 responses), diazepam (31 responses) and propofol (15 responses).  Twelve respondents combined opiates and benzodiazepines, whilst seventeen combined local anaesthesia with sedation (Table 1).  Two-thirds of respondents (35 out of 53, 66%) administered sedation in boluses rather than calculating the correct dose per kilogram.  The pharmacology questions devised by Fanning⁸ tested knowledge of metabolic pathways, duration of action and side effects. Overall, each question was answered correctly by over 50% of respondents (Figure 3).  The mean score was 4.29 out of 7.

Figure 3The percentage of correct answers for each of the seven pharmacology questions.

Eighty percent of surveyed orthopaedic doctors (43 respondents) reported an adverse event after administering sedation.   Twenty-nine respondents had at some stage contacted the anaesthetic department for assistance in managing a patient following sedation (Table 2).

Table 2:  Adverse Events reported.

Discussion

Non-anaesthetic doctors are permitted and often required to administer sedation to perform procedures in settings outside of the operating theatre.  There are various published guidelines that detail the level of care and monitoring that should be provided when sedation is given^3-7.  It has been recommended that the same standards of monitoring apply to procedures under sedation or local anaesthesia as to procedures under general anaesthesia, and are irrespective of the location of the procedure³.

The report by an intercollegiate working party led by the Royal College of Anaesthetists summarised the key aspects of administering sedation based on existing guidelines⁶.  Patients should be first assessed before the procedure by attendant staff, risk factors noted and further examination or investigations performed as necessary.  Drug administration technique should be “one defined by a relevant specialty organisation”⁶ and doses adjusted to individual patient requirements.  Combinations of drugs should be “employed with particular caution” especially sedatives and opioids.  The opioids should be administered first and given time to be maximally effective before any sedative is given.  The patient should be monitored during the procedure by a suitably trained individual recording pulse oximetry, blood pressure and electrocardiography. High flow oxygen should also be available. Doctors administering sedation should be able to control an airway using basic manoeuvres or airway adjuncts.

There is significant morbidity and mortality associated with sedation^1,2.  It is difficult to know the true incidence of cardio-respiratory complications after sedation, as this is often related to the procedure and patient factors.  An audit of 14,000 endoscopic procedures reported a 30-day mortality of 1 in 2000⁹ and there are several anecdotal reports of death following sedation^10,11.

It is apparent that not all doctors are aware of or follow sedation guidelines.  In the study by Fanning⁸, 42% of respondents completed a pre-procedure assessment form and 70% completed monitoring data sheets.  In this study, whilst 45% of respondents had read departmental protocols, only 25% completed a dedicated pre-assessment of the patient and an equally low number recorded monitoring data forms during (21%) and after the procedure (25%).  These low numbers are of potential concern.  Time and resource constraints may play a part, particularly in a busy emergency department.  Also, as junior doctors frequently rotate between hospitals, they may not be aware of departmental policies in each unit.  It is understandably impractical to perform a procedure and concurrently complete a data monitoring form.  This role should be delegated to an assistant.

Knowledge of basic pharmacology amongst respondents seemed reasonable and indeed better scores were achieved than in Fanning’s original paper.  It would appear that a large number of respondents (n=29) have contacted anaesthetic colleagues for help following adverse events.  This may simply reflect an acknowledgement of limited anaesthetic capabilities amongst respondents and a pre-emptive call for assistance rather than an anaesthetic “bail out” after cardio-respiratory compromise.

Whilst the questionnaire used is neither a formal assessment tool of clinical competence nor an accurate log of experience, it serves to highlight the potential limitations of current training.  A clear issue is the low number of respondents who claim to have received formal teaching or training with regards to sedation.  This may be due to the fact that little or no postgraduate training is provided in hospital specialities that require sedation. This is an area that needs to be addressed.  The issues raised by this study are not new.  In fact, a similar survey by Hewitt and Hartley in 1994 had similar findings and suggested that “sedation techniques should be included in induction teaching for A&E and orthopaedic juniors” and that all doctors administering sedation should have the “opportunity of resuscitation refresher courses”¹². 

Conclusion

Sedation is widely administered by non-anaesthetic doctors including orthopaedic surgeons in order to perform basic procedures outside of the operating theatres, mainly in the Accident and Emergency department.  Whilst this study only involves 53 doctors in one speciality across two regions, it does give an insight into the self-reported clinical practice, knowledge and experience of a group of surgical doctors who are often required to administer sedation.  Significantly, the majority of doctors surveyed reported they had not received any formal training.  It is also apparent that departmental guidelines are not always known or followed.  Due to the inherent risks of sedation, it is important that doctors are aware of and follow available guidelines.  It is crucial that adequate training should be given to non-anaesthetic doctors to ensure they have the knowledge and skills to safely administer sedation. Otherwise a medical doctor, perhaps a registrar level from the Accident and Emergency department, should be present for patient assessment and management of airway compromise or any arising complication.

Introduction

Tumefactive multiple sclerosis (MS) is a rare variant of MS.  This form of MS can masquerade as neoplasm or infectious etiology.  Understanding of the disease is limited to case report but it is associated with high morbidity and mortality.

Case report

A 44 year old man presented with a 2-month history of progressive right upper extremity weakness, confusion and visual change.  Physical exam revealed weakness, hyperreflexia on the right side and right homonymous hemianopia.  MRI of the brain showed multiple ring-enhancing lesions located in both cerebral hemispheres.  CSF analysis disclosed elevated protein with positive oligoclonal bands and myelin basic protein.  Stains and cultures for bacteria and mycobacteria were negative.  Serologies including HIV, Toxoplasmosis, and Lyme were all negative.  Patient was treated with high-dose IV corticosteroid and clinically improved.  One month later, he presented with increasing confusion, aphasia and progressive weakness.  Repeat MRI of the brain revealed worsening multiple ring-enhancing lesions with surrounding vasogenic edema in most lesions.  High-dose corticosteroid was promptly started.  There was also concern about infection, especially brain abscess; hence, intravenous ceftriaxone, vancomycin, and metronidazole were empirically given.  Due to uncertainty of diagnosis, first brain biopsy at right frontal lobe lesion yielded non-specific gliosis.  Repeat MRI brain showed increasing number of ring-enhancing lesions in both cerebral hemispheres.  As a result, a second brain biopsy was performed, which showed an active demyelinating process consistent with multiple sclerosis.  Patient experienced severe disability and was discharged to long-term facility with slowly tapered schedule of corticosteroid. He was readmitted several times and eventually family decided hospice care.

Discussion

Multiple sclerosis is diagnosed by demonstrating clinical and/or radiographic evidence of dissemination of disease in time and space¹.  Tumefactive MS is a term used when the clinical presentation and/or MRI findings are indistinguishable from a brain tumor².  Not all case of tumefactive MS are fulminant.  Marburg variant MS is an acute rare variant of MS which has a rapidly progressive course with frequent, severe relapses leading to death or severe disability within weeks to months³.  The tumefactive demyelinating lesions are defined as large (>2 cm.) white matter lesions with little mass-like effect or vasogenic edema, and post-gadolinium magnetic resonance imaging (MRI) typically showing an incomplete ring enhancement^2,4.  The clinical and imaging characteristics of these demyelinating lesions may mimic primary and secondary brain tumors, brain abscess, tuberculoma, and other inflammatory disorders e.g. sarcoidosis, primary sjogren’s syndrome⁵. As a result, tumefactive MS is frequently misdiagnosed. There are some MRI characteristics that are more suggestive of tumefactive demyelinating lesions than of other etiologies.  These include incomplete ring enhancement, mixed T2-weighted iso-and hyperintensity of enhanced regions, absence of a mass effect and absence of cortical involvement^2,6.   Differential diagnosis of rapidly progressive neurological deficit with ring-enhancing lesions include brain abscess, primary brain neoplasm or brain metastasis, acute disseminated encephalomyelitis (ADEM) and tumefactive multiple sclerosis.  Careful clinical history, CSF study, serial MRI evaluation and follow-up are usually sufficient to make a diagnosis. Some cases pose considerable diagnostic difficulty owing to clinical and radiographical resemblance to brain tumor, for which biopsy may be warranted.  Pathologically, the lesions are characterized by massive macrophage infiltration, acute axonal injury, and necrosis.  No specific histological features distinguished specimens derived from patients developing classic multiple sclerosis from those who had tumefactive form⁷.  A limited number of cases of Marburg’s variant MS have been reported in the literature whereby most patients died within a period of weeks to months.  Only two cases survived after one year^7,8.  There is no current standard treatment for this condition.  Plasma exchange and Mitoxantrone are reportedly showed some promising options^9,10.

Figure A: FLAIR imaging at first presentation showed lesion in both hemisphere. Figure B: FLAIR imaging at one month later showed progression of multiple lesion in both hemisphere. Figure C: T1 Post contrast imaging showed intense ring enhancement pattern in almost all lesions  with mild edema and minimal mass effect. Figure D: Showed lesion view as sagittal section.

Our patient presented somewhat like a stroke with visual field defect and right hemiparesis which is unusual in MS, but MRI and CSF exam yielded a diagnosis of probable MS.  Because of his abrupt clinical deterioration and impressive worsening of his MRI, concern was raised about possibility of infection or neoplasm.  Hence, he received two brain biopsies, the second of which showed active demyelination, confirming the diagnosis of severe tumefactive multiple sclerosis and can be consider as a Marburg variant multiple sclerosis.

Conclusion

Marburg variant multiple sclerosis carries a high morbidity and mortality.  This disease notoriously mimics other conditions leading to delay diagnosis and treatment.  Absence of definitive diagnosis test apart from brain biopsy makes diagnosis, prognosis and treatment decisions difficult. 

Introduction

Patients with morbid obesity suffer a wide range of symptoms that relate to their oesophagus and stomach. It is rather paradoxical that patients who are overweight suffer the symptoms of difficulty in swallowing, pain during eating or pain after eating because the symptoms of eating difficulty do not translate into weight reduction. There are a range of underlying causes that include gastro-oesophageal reflux disease, dysmotility in the oesophagus, peptic ulceration and the nature and pattern of dietary intake.  The pathophysiology of gastro-oesophageal reflux disease and of dysphagia will be considered. The detrimental effects of the treatments of balloons, gastric bands and gastric bypass will be described and options for management discussed.  The serious complications of adenocarcinoma and its premalignant precursor, Barrett’s oesophagus will be reviewed.

Gastro-oesophageal reflux disease (GORD)

GORD is highly prevalent in obese people with increasing BMI a risk factor for developing the disease. The relation between GORD and obesity has been studied for decades and there have been conflicting results. A person with BMI of ³30 kg/m²   is 3 times more likely to suffer from heartburn and acid regurgitation ¹.

Though the mechanism of this is poorly understood, a number of epidemiological studies have proven this association. Since recently, more evidence has emerged in favour of a positive association ². In 2000, Lagergren et al, based on a population based interview study on 820 Swedish, concluded that GOR symptoms occurred independent of BMI ³. His claim was supported by two previous studies, one of which used oesophageal pH measure and other assessed the impact of weight loss on symptom relief ^{4, 5}. A contrary view has emerged since this, with large number of western studies showing a positive association ^{1, 2, 6-12}. This, however, has not been the case with Asian and Afro-Caribbean population. In a large population study with various ethnicities, a strongly positive association was found between BMI and GOR symptoms in white population. This was not the case in Asian and black population ¹³, a view re-iterated by another study from Iran ¹⁴. The overall incidence of GORD is high in western world between 10% and 20%, compared to 5% in Asia ⁶.

The mechanism of GORD in obesity is very poorly understood. Various theories have been postulated and the evidence for each is discussed below, including the theory that the patho-physiology of reflux in the morbidly obesity could differ from others and might require a different therapeutic approach ⁹

Increased intra-abdominal pressure as a cause of reflux

Increasing intra-abdominal pressure has been hypothesised to be the cause for reflux symptoms. Increasing BMI has been shown to increase intra-gastric pressure and pressure study in a prospective cohort has shown 10% increase in intra-gastric pressure with rise in each unit of BMI ¹⁵. A pH and manometry study in general population with GORD showed a higher pressure gradients across the Oesophago-gastric junction than that in controls both before and during transient lower oesophageal sphincter relaxation. This phenomenon is thought to be caused by increased intra-gastric pressure, supporting the above theory ¹⁶.

Lower oesophageal sphincter dysfunction as a cause

Kuper et al showed a dysfunction of LOS and altered oesophageal motility even in asymptomatic patients with morbid obesity using pH and manometry study (BMI >40 kg/m²) ¹⁷and Wu et al showed an abnormal post-prandial LOS with prolonged transient lower oesophageal relaxation ^{18, 19}.These findings were re-iterated by ayazi et al, showing obese patients to be more than twice as likely to have a mechanically defective LOS ²⁰.   However, another study back in 1987 had shown a similar LOS pressure in normal weight and obese patients, though the gastro-oesophageal pressure gradient to LOS pressure ratio was high in obese ²¹.

Diet

The amount or composition of dietary intake and its relation to GORD has been studied. There is some evidence that volume, fat content and a high-caloric diet increases the oesophageal acid exposure time, giving rise to symptoms ^22-24. This would suggest an improvement of symptoms with reduction of these in the diet. More studies have shown an improvement in reflux symptoms with improved diet ^25-29. But, there is no convincing evidence to implicate the role of diet in reflux symptoms of obese patients.

Hiatus hernia

The incidence of hiatus hernia is over 50% in morbid obesity ³⁰. Hiatus has been shown to be predicted by intra-gastric pressure, gastro-oesophageal presssure gradient and BMI. BMI has in turn been shown to predict the former two. This confirms a positive association between BMI and presence of hiatus hernia ³¹. High BMI is more likely to have oesophago-gastric junction disruption, leading to hiatal hernia and an augmented gastro-oesophageal pressure gradient, providing a perfect scenario for reflux to occur ³². The incidence of defective LES was twice as much in obese patients with hiatus hernia, compared to obese without it ²⁰. Hiatus hernia thus plays a role in the obese patients and the subsequent development of GORD ³³.

Poor mobility and mental state

There is no evidence to support the theory of reflux symptoms secondary to poor mobility and depression in the morbidly obese patients.

Treatment of GORD in obesity

Medical therapy

Medical therapy with a PPI remains the first line of treatment of GORD symptoms in obesity as in patients with a normal BMI. No guidelines are available for dose adjustments in the obese patients ³⁴. They continue to receive the standard therapy, adjusted to the severity of disease and symptoms.

Endoluminal therapy

Endoluminal therapy was introduced recently as treatment alternative for GORD and has shown promising results. This looked a safe option for use in obese patients. However, published results have shown high rate of post-operative PPI requirement in the obese patients ³⁵. Further evidence has to emerge before this option can be recommended for use in the obese patients.

Balloon

Intra-gastric balloon therapy has been an established temporary procedure for weight loss. GORD symptoms in obese tends to improve with weight loss, but as studies have shown, a balloon insertion tended to worsen symptoms ^{36, 37}. Balloon is hence not considered an option for treatment of obesity with patients with reflux symptoms.

Gastric band

Gastric banding provides a sufficient anti-reflux barrier in most of the obese patients with GORD. Abnormal manometric findings like increased LES (lower oesophageal sphincter) residual pressure and peristaltic wave duration are frequently encountered after banding. The clinical significances of these manometric abnormalities are not clear ³⁸. The oesophageal stasis caused by the band could explain the reflux in patients during longer follow up. Though, the reflux from the distal stomach is prevented by the gastric band, formation of a proximal pouch predisposes to stasis and reflux. This is more common in patients with preoperatively defective oesophageal motility. The studies suggesting a good GORD symptom control following banding had shorter follow up, explaining the results ^{39, 40}. Hence it could be concluded that gastric banding may aggravate GORD symptoms and cause oesophageal dilatation, especially in patients with pre-operative motility defects. Routine pre-operative testing should be done and alternative bariatric surgical procedures such as Roux-en-Y gastric bypass considered in these patients   ^41-43.

Sleeve Gastrectomy (Vertical gastric banding)

Gastrectomy reduces weight, but not gastro-oesophageal acid reflux. Although this procedure has been shown to have anti-reflux properties ⁴⁴, it has fallen to disrepute in terms of relieving the reflux symptoms, especially with the superior results of RYGB ^45-48. A number of these cases requiring revision, due to reflux symptoms, have been reported ^49-51.

Gastric Bypass Vs Anti-reflux surgery

Though laparoscopic fundoplication is the standard operation for GORD, gastric bypass has been shown to improve the reflux symptoms in the morbidly obese, apart from reducing their weight and obesity related co-morbid conditions such as diabetes mellitus, hypertension etc. Patterson et al. showed an equivalent symptomatic improvement and objective DeMeester score improvement with Laparoscopic Nissen fundoplication and laparoscopic gastric bypass. The LES (lower oesophageal sphincter) pressure was also noted to improve, following bypass ⁵². This was in light of an earlier report of 31% recurrence rate of reflux symptoms following laparoscopic Nissen’s in obese patients ⁵³. Hence, morbidly obese patients with GORD should be offered laparoscopic gastric bypass as a surgical option ^{27, 30, 54-59}.

The improvement in GORD symptoms after gastric bypass is related to the way that the operation staples off the distal 90% or more of the stomach body and antrum, removing any possibility that acid generated in this part of the stomach can reach the oesophagus.  The parietal cell mass within the small gastric pouch that is left attached to the oesophagus, the complete elimination of duodeno-gastric reflux owing to a long Roux limb, and decrease in intra-abdominal pressure with weight loss all contribute to an almost total reflux control in all patients. The overall complications secondary to this procedure were lower than in laparoscopic fundoplication ⁵⁴. It is also the procedure of choice for previous other weight-loss surgery, when reflux symptoms develop ^49-51. Thus, a bariatric team prior to surgical intervention should review obese patients with GORD symptoms.

Dysphagia in obesity

Dysphagia in obesity is often related to the interventions used to treat obesity, though it can be primary in nature.

Various modalities of interventions available in obesity have been discussed above. Intra-gastric balloon therapy can be complicated by its displacement into the distal stomach, precipitating dysphagia and outlet obstruction. Gastric bands can be overfilled, causing this problem, and a slipped band or a band eroding through the stomach wall can also lead to dysphagia ^60-64. There has been no report of gastric bypass resulting in dysphagia, in the literature.

It is our understanding that patients with obesity may present with primary oesophageal dysmotility. Although there is little published literature on this issue, it is our hypothesis that fatty infiltration of the oesophageal wall and myenteric plexus may result in a poor amplitude peristaltic contraction.

Other oesophageal conditions associated with obesity

Barrett’s Oesophagus

This is characterised by the replacement of the normal squamous epithelium of the lower oesophagus by a specialised metaplastic columnar epithelium. Barrett’s oesophagus is a known risk factor for oesophageal adenocarcinoma, with a 30 to 125 times increased risk compared to general population ⁶⁵. Risk factors leading to Barrett’s have been poorly understood, though GORD is widely believed to be the main risk factor ^66-68. Since several studies have found an association between obesity and GORD ^{1, 2, 6-12}, and obesity as a risk factor for Barrett's have gained momentum in the recent year. Abdominal obesity or waist circumference has been shown to be more associated with Barrett’s than BMI ⁶⁹.

A recent systematic review showed a statistically significant relation between increasing BMI and Barrett’s ⁷⁰. However, two older systematic reviews had found a rather week relation between these two, showing a need for further well designed studies ^{71, 72}. To mention a few studies, Jacobson et al showed a positive relation between BMI and Barrett’s in women, independent of GORD, though the waist circumference was not found to have any association ⁷³and Stein at al., found a positive relation between BMI and Barrett’s in war veterans ⁷⁴. Abdominal obesity or circumference appears to be more influential in the incidence of Barrett’s oesophagus in another study ⁷⁵. There is however, little evidence to suggest an increased progression of Barrett’s to neoplasia in obesity ⁶⁹

Obesity is a modifiable risk factor and if proven to be a risk for Barrett’s and subsequent neoplasia, resources can be directed at modifying this, as there is evidence to suggest the regression Barrett’s with weight loss ⁶⁹. Barrett’s have been shown to regress with weight loss following gastric bypass and hence this has been recommended as bariatric procedure of choice in the morbidly obese with Barrett’s ^76-79. A precise endoscopic evaluation before bariatric surgery with continuing postsurgical surveillance in patients with known Barrett's oesophagitis, and early evaluation in patients who develop new symptoms of GERD after bariatric surgery is suggested ^{80, 81}

Adenocarcinoma of oesophagus

The incidence of oesophageal adenocarcinoma has increased about 400% during the past three decades, the most rapid rate of increase of any cancer in the United States ^82-84. The association between high BMI and oesophageal adenocarcinoma is strong and well established, though the mechanism of this is still unclear. The risk is higher with increasing BMI, especially in men ^85-94. Obesity has also been shown to play a role in adenocarcinomas with a family history ⁹⁵. The incidence of adenocarcinoma of the cardia of stomach has not been so strongly related to BMI ^{96, 97}. Squamous cell carcinoma of oesophagus has not shown any association to obesity either ^{85, 93, 94, 98, 99}. Few studies have negated the association of obesity with oesophageal adenocarcinoma, but many were due to the fact that they included oesophageal and proximal stomach together ⁹⁶. The majority of these cancers arise from a background of premalignant Barrett’s oesophagus, though less than 10% of the patients with oesophageal adenocarcinoma were known to have Barrett’s oesophagus previously. Presently there is no evidence that strongly supports any specific strategy to screen a subgroup of the population at risk for Barrett’s oesophagus and adenocarcinoma of the oesophagus ¹⁰⁰.

A number of studies have also looked at the mechanism or pathway of this metaplasia-dysplasia-adenocarcinoma sequence.  Visceral adiposity rather than BMI is thought to have a greater role in chronic inflammation and subsequent neoplasia. It has a clear association with Barrett’s as above. Increasing abdominal girth increases the risk of adenocarcinoma and it has been shown for Barrett’s ⁹⁸. Visceral fat is hypothesised as a major producer of interleukin-6, adinopectin, leptin and other adipokines that may be associated with the development of various gastro-intestinal cancers ^101-103. More specifically, insulin-like growth factor has been implicated in the pathogenesis of adenocarcinoma in the obese ¹⁰⁴. Oesophago-gastric tumours after bariatric surgery, has been reported, though rare. This condition, when occurs, requires the close collaboration of the bariatric team to achieve a successful oncological result, due to the altered anatomy like the blood supply to the gastric pouch and excluded stomach ¹⁰⁵.

Conclusion

Obesity is associated with oesophageal disease, benign and malignant, and both the effects of obesity and the effects of it’s treatment can aggravate oesophageal symptoms. The management of reflux and of dysphagia in obese patients requires a broad understanding of these issues.

Introduction

Infection of a prosthetic total knee joint is a serious complication¹ and should be diagnosed promptly² and treated aggressively. We present an interesting case of MRSA infection of a primary total knee replacement following  an IV cannula infection leading to bacteremia and subsequent infection of  the knee prosthesis, complicated by stevens- Johnson syndrome .

There were many challenging issue which are outlined including diagnosis and management.

Case Report

A 63-year- old lady had an elective total knee arthroplasty for severe osteoarthritis of the knee. She had a background history of well-controlled type 2 diabetes mellitus and was on warfarin for a previous pulmanory embolism. As per the hospital protocol her warfarin was stopped before surgery until her INR was <1.5 and she was heparinised with a view of

warfarinizing after the surgery. She had an uneventful knee arthoplasty, but unfortunately one of her IV cannula site became cellulitic. She was empirically started on oral flucloxacillin after taking blood cultures and sending the cannula tip for microscopic culture and sensitivity (which is routinely done has hospital protocol for infected cannula sites).

Surprisingly the tip grew MRSA and also had MRSA bacteraemia. She became systemically unwell and septic, and was treated aggressively with parentral vancomycin for MRSA bacteraemia. She had a transeosphageal echocardiogram to rule out cardiac vegetation. She gradually improved but developed typical papular rashes over her palm, dorsum of hand, extensor surface of arm and forearm and trunk and buccal mucosa (Fig 1 and 2) .

Fig 1: Rash over the dorsum hands

Fig 2: Rash over the extensor aspects of forearm

She had a severe allergic reaction to vancomycin and the skin biopsy of the lesion confirmed that she had developed Stevens-Johnson syndrome. An alternative antibiotic was started following discussion with the specialist bone infection unit. She gradually improved over the next few weeks without any problem in her prosthetic replaced knee. At about 6 weeks post- operatively she developed severe pain and hot swelling of her replaced knee with decrease range of motion. Her inflammatory markers were markedly raised and the knee aspirate confirmed MRSA infection of the total knee replacement. She was referred to a specialist bone infection unit due to the complexity of the case, where she successfully underwent two- stage revision.

Discussion

Infection of  a Knee replacement is a serious complication that requires significant hospital-based recourse for successful management³. The rate of infection of a primary knee replacement varies from 0.5- 12%¹. Rheumatoid arthritis , previous surgery , diabetes mellitus are all associated with an increased risk of infection ⁴. Although there is no absolute diagnostic test for peri-prosthetic infection² , a high index of clinical suspicion is essential. There has been a case report on MRSA cervical epidural abscess following IV cannulation ⁵, but to the best of our knowledge there has been no previous report of MRSA- infected knee arthroplasty following complications of IV cannulation. Stevens-Johnson syndrome involves rare but severe cutaneous adverse reactions related to a variety of medications including antibiotics⁶. Parenteral vancomycin is the first line treatment for MRSA bacteraemia. It is recognised that vancomycin is indicated in inducing Stevens -Johnson syndrome, mortalitiy being 30-100%⁷. It is vital that Stevens- Johnson syndrome is recognised early so that offending agents are stopped and supportive treatment commenced. Early dermatological consultation, skin biopsy and direct immunofluorescence⁷ are essential to confirm diagnosis  so that effective treatment can be instituted.The diagnosis and management of this serious complication is complex and requires considerable recourse allocation by the patient, the hospital, the infectious disease specialist, and the orthopaedic surgeon^1,5.