Dec

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.

General Information 

1. Vertigo is the hallucination of movement of the environment around the patient, or of the patient with respect to the environment ¹. It is not a fear of heights.
2. Vertigo is not necessarily the same as dizziness
3. Dizziness is a non-specific term which can be categorised into four different subtypes according to symptoms described by the patients:
   
   1. Vertigo
   2. Presyncope: the sense of impending faint, caused by a reduced total cerebral perfusion
   3. Light-headedness: often described as giddiness or wooziness ²
   4. Disequilibrium: a feeling of unsteadiness or imbalance when standing ²

Classification Vertigo may be classified as:

1. Central - due to a brainstem or cerebellar disorder
2. Peripheral - due to disorders of the inner ear or the Vestibulocochlear (VIII^th) cranial nerve

Incidence/Prevalence: Most patients who complain about dizziness do not have true vertigo:

1.    5 community based studies into dizziness indicated that around 30% of patients were found to have vertigo,     rising to 56.4% in an older population ³
2.   A postal questionnaire study which examined 2064 patients, aged 18-65, 7% described true vertigo in the       previous year ³
3.   A full time GP can therefore expect between 10-20 patients with vertigo in one year ³
4.   93% of primary care patients with vertigo have either benign paroxysmal positional vertigo (BPPV), acute         vestibular neuronitis, or Ménière's disease ⁴. These conditions are highlighted in Table 2 

Causes A wide range of conditions can cause vertigo, and identifying whether deafness or CNS signs are present, can help narrow the differential diagnosis, as shown in Table 1. 

 Symptoms 

1. Vertigo may be due to central lesions or peripheral lesions. Vertigo may also be psychogenic or occur in conditions which limit neck movement, such as vertigo caused by cervical spondylosis, or following a “whiplash” flexion-extension injury.
2. It is essential to determine whether the patient has a peripheral or central cause of vertigo ¹.
3. Information obtained from the history that can be used to make this distinction includes ¹: 
   
   1. The timing and duration of the vertigo
   2. Provoking or exacerbating factors
   3. Associated symptoms such as
      
      1. Pain
      2. Nausea
      3. Neurological symptoms
      4. Hearing loss
4. Central vertigo:
   
   1. The vertigo usually develops gradually
   2. Except in: an acute central vertigo is probably vascular in origin, e.g. CVA
   3. Central lesions usually cause neurological signs in addition to the vertigo
   4. Auditory features tend to be uncommon.
   5. Causes severe imbalance
   6. Nystagmus is purely vertical, horizontal, or torsional and is not inhibited by fixation of eyes onto an object
5. The duration of vertigo episodes and associated auditory symptoms will help to narrow the differential diagnosis ⁵. This is illustrated for various pathologies that cause vertigo, in Table 2
   

   Table 2 Timing of symptoms
   Pathology	Duration Of Episode	Associated Auditory Symptoms	Peripheral or Central Origin
   Benign Paroxysmal Positional Vertigo	Seconds	No	Peripheral
   Vestibular Neuronitis	Days	No	Peripheral
   Ménière's Disease	Hours	Yes	Peripheral
   Perilymphatic Fistula	Seconds	Yes	Peripheral
   Transient Ischemic Attack	Seconds / Hours	No	Central
   Vertiginous Migraine	Hours	No	Central
   Labyrinthitis	Days	Yes	Peripheral
   Stroke	Days	No	Central
   Acoustic Neuroma	Months	Yes	Peripheral
   Cerebellar Tumour	Months	No	Central
   Multiple Sclerosis	Months	No	Central

   It is important to differentiate vertigo from non-rotatory dizziness (presyncope, disequilibrium, light-headedness). Patients can be asked whether they “felt light headed or felt as if the world was spinning around” during a dizzy spell ³.

6. Important points in the history:
   
   1. Onset - specific provoking events such as flying or trauma
   2. Duration:
      
      1. Seconds - Benign positional vertigo
      2. Hours - Ménière's Disease
      3. Weeks - Labyrinthitis, Post-head trauma, Vestibular neuronitis
      4. Years - may be psychogenic
   3. Associated auditory symptoms - rare in primary CNS lesion
   4. Other associated symptoms
      
      1. Nausea and vomiting in a vestibular cause
      2. Neurological symptoms such as visual disturbance, dysarthria in a central lesion

Physical/signs 

1. Examination of ear drums (Otoscopy/ Pneumatic otoscopy) for:
   
   1. Vesicles (Ramsay Hunt syndrome)
   2. Cholesteatoma
2. Tuning fork tests for hearing loss – Rinne/Weber tests
3. Cranial nerve examination. Cranial nerves should be examined for signs of :
   
   1. Nerve palsies
   2. Sensorineural hearing loss
   3. Nystagmus ³ 
4. Hennebert's sign ¹
   
   1. Vertigo or nystagmus caused by pushing on the tragus and external auditory meatus of the affected side
   2. Indicates the presence of a perilymphatic fistula.
5. Gait tests:
   
   1. Romberg's sign (not particularly useful in the diagnosis of vertigo ¹)
   2. Heel-to- toe walking test
   3. Unterberger's stepping test ¹ (The patient is asked to walk on the spot with their eyes closed – if the patient rotates to one side they have labyrinth lesion on that side
6. Dix-Hallpike manoeuvre ¹
   
   1. The most helpful test to perform on patients with vertigo¹
   2. If rotational nystagmus occurs then the test is considered positive for BPPV. During a positive test, the fast phase of the rotatory nystagmus is toward the affected ear, which is the ear closest to the ground.
7. Head impulse test/head thrust test
   
   1. Useful in recognizing acute vestibulopathy ⁶
8. Caloric tests
   
   1. Cold or warm water or air is irrigated into the external auditory canal
   2. Not commonly used

Investigations/Testing to consider:

1. Special auditory tests
   
   1. Audiometry helps establish the diagnosis of Ménière's disease
2. The history is most important and may give a quite good indication of the cause of vertigo. General medical causes such as anaemia, hypotension and hypoglycaemia may present with dizziness, and therefore should be investigated.
3. If features of CNS causes is suspected from the history or examination:
   
   1. CT/MRI Brain imaging as appropriate

Treatment 

1. Treatment should ideally aim at the cause of the vertigo ⁷:
   
   1. Medical management – as described below.
   2. Vestibular rehabilitation exercises – e.g. Cawthorne-Cooksey exercises ⁵.
      
      1. These exercises aim to help the patient return to normal activity more quickly.
      2. Moving the eyes from side to side and up and down while in bed or sitting down - then moving the head, first with your eyes open and then closed
      3. Other forms use gaze and gait stabilising exercises. Most exercises involve head movement

2. For most patients the main priority is effective control of the symptoms.
   
   1. For acute attacks, treatments include ^5,8: -
      
      1. Betahistine hydrochloride 8-16mg upto TDS
      2. Cinnarizine, 15-30 mg TDS or
      3. Prochlorperazine should be reserved for rapid relieve of acute symptoms only ^8,12 - tablets 5-10 mg or buccal 3mg TDS or injection 12.5 mg IM or 25mg PR suppository - if vomiting
   2. Preventive measures for recurrent attacks include:
      
      1. Restrict salt and fluid intake - stop smoking and restrict excess coffee or alcohol ^9,10
      2. Betahistine hydrochloride 16mg regularly TDS seems most effective in Ménière's
      3. Cinnarizine 15-30 mg TDS
   3. Points to consider
      
      1. Warn patients when drugs may sedate ¹⁰.
      2. Prochlorperazine is less sedating than some other recommended antihistamines, but may cause a dystonic reaction (particularly in children and young women) ¹¹.
      3. Benzodiazepines are not recommended ⁹.
   4. Recurrent vertigo
      
      1. The most important first step in the management of recurrent vertigo is to distinguish vertigo from 'dizziness'.
      2.  In attacks of vertigo there is a sense of mobile disequilibrium ("the room spinning") which, if severe, results in uncontrolled staggering in one direction which may be only prevented by grabbing a solid object ¹⁰.
   5. Epley's manoeuvre

         a.     Aims to remove debris from the semicircular canals and deposit it in the utricle where hair cells are not                     stimulated ¹¹      b.     Contraindications include ¹⁰:                                         i.     Severe carotid stenosis                                         ii.     Unstable heart disease                                         iii.    Severe neck disease (cervical spondylosis with myelopathy)                                         iv.    Advanced rheumatoid arthritis Consultation and referral:
   

   1. Refer to secondary care if ¹⁰ :
      
      1. Recurrent separate episodes
      2. Neurological symptoms e.g. dysphasia, paraesthesiae or weakness
      3. Associated sensorineural deafness
      4. If there is an inadequate visualisation of the entire tympanic membrane or an abnormality (e.g. cholesteatoma)
      5. Atypical nystagmus e.g. non-horizontal, persisting for weeks, changing in direction or differing in each eye
      6. Positive fistula sign: pressure on the tragus reproducing symptoms (suggests endolymphatic fistula
   2. If the patient has hearing problems in addition to vertigo then referral should be made to an ENT specialist. Other cases should be referred to a neurologist ¹⁰.
   3. While awaiting referral:
      
      1. Consider symptomatic drug treatment  for no longer than 1 week because prolonged use may delay vestibular compensation
      2. It is important that the person stops symptomatic treatment 48 hours before seeing a specialist, as it will interfere with diagnostic tests such as the Dix-Hallpike manoeuvre.
      3. If the person's symptoms deteriorate, seek specialist advice.

   When to consider hospitalization
   

   1. Admit the patient to hospital if they have severe nausea and vomiting, and are unable to tolerate oral fluids ⁹.
   2. Admit or urgently refer the person to a neurologist if they have:
      
      1. Very sudden onset of vertigo (within seconds) that persists.
      2. Acute vertigo associated with neurological symptoms or signs (e.g. new type of headache - especially occipital, gait disturbance, truncal ataxia, numbness, dysarthria, weakness) which may suggest CVA, TIA, or multiple sclerosis ⁹.
   3. Admit or refer the person as an emergency to an ENT specialist if they have acute deafness without other typical features of Ménière’s disease (tinnitus and a sensation of fullness in the ear). Sudden onset unilateral deafness would suggest acute ischaemia of the labyrinth or brainstem, but can also occur with infection or inflammation.
      
      1. Emergency treatment may restore hearing. The person should be seen within 12 hours of the onset of symptoms ⁹
   4. The urgency of referral depends on the severity of symptoms (e.g. requirement for intravenous fluids because of excessive vomiting) and the suspected diagnosis ⁹.

    Patient InformationThe Ménière's Society www.menieres.org.ukwww.patient.co.uk/doctor/Vertigo.htm

    

Richard D Griffiths BSc, MD, FRCP, FHEA

Prof Griffiths is a Professor of Medicine (Intensive Care), Dept of Musculoskeletal Biology, Institute of Ageing & Chronic Disease, Faculty of Health & Life Sciences University of Liverpool, and Honorary Consultant Physician in Intensive Care Medicine, Whiston Hospital, UK.
 
He obtained a BSc in Physiology during undergraduate training in medicine (MBBS) at University College London during the ‘70s. During the early ‘80s in London obtained a research MD studying muscle energetics in the early days of human Magnetic Resonance Spectroscopy. Became a consultant in adult Intensive Care Medicine in 1985 following a move to Liverpool in 1984 and continued research interests in muscle and expanded these into nutrition (glutamine) and the critically ill. Since then has been a pioneer of the rehabilitation of the post-ICU patient. He extensively involved over the last two decades in undergraduate curriculum reform and as the Director of the Final Year has pioneered a fully portfolio based professional learning programme.
 
How long have you been working in your speciality?
I have been a consultant intensive care physician for more than 25 years.
 
Which aspect of your work do you find most satisfying?
To be able to improve patient care through clinical research and the training of medical students.
 
What achievements are you most proud of in your medical career?
Raising the awareness of the physical, psychological and cognitive challenges ICU patients and relatives face during recovery and contributing to the evidence base guiding rehabilitation.Clinical nutrition research on glutamine and identifying the need to use six month mortality outcomes in the critically ill. Creating a final year of undergraduate medical training that fosters professionalism and critical self awareness based upon a clinical portfolio and appraisal process that produces graduates fit for practice.  
 
Which part of your job do you enjoy the least?
Very little, but perhaps the ever increasing bureaucracy of regulation in practice and research.
 
What are your views about the current status of medical training in your country and what do you think needs to change?
In the UK most medical schools have radically reformed their curriculum to meet the needs of modern medicine and life- long learning. In Liverpool our students are recognized to be well prepared with the skills to ensure patient safety and start foundation training following a course commended by clinicians, hospitals, examiners and GMC alike. Post-graduate changes have paralleled these developments and while the training structures and closer observations are to be commended the restrictions on working time remains a concern for the acquisition of real “shop floor” experience. Our trainees simply don’t get enough “flying hours” as in the past.
 
How would you encourage more medical students into entering your speciality?
Intensive care medicine is popular. The problem for students is to understand how to get there. The new Faculty of Intensive Care medicine, that has just starte, brings an independent speciality out from under the umbrella of its various parent specialities and hopefully will provide the focus to make the career pathway clearer in the future.
 
What qualities do you think a good trainee should possess?
All those attributes that the GMC expect of a practitioner! In particular I like to see enthusiasm, self awareness and measured confidence, an enquiring and questioning mind and a degree of professional flexibility mixed with the ability to ask for help and advice. I need to trust them just as their patients need to as well.
 
What is the most important advice you could offer to a new trainee?
Stay calm, be professional and follow the basic principles of good medical practice doing the simple things well, and don’t be afraid to ask for help.
 
What qualities do you think a good trainer should possess?
Maintain professionalism and be a role model at all times with the ability to listen, support and recognize the strengths as well as being firm with those things that need developing.
 
Do you think doctors are over-regulated compared with other professions?
No, while regulation does not itself prevent bad medicine it does prevent it being ignored.
 
Is there any aspect of current health policies in your country that are de-professionalising doctors? If yes what should be done to counter this trend?
De-professionalising only occurs when doctors avoid taking leadership roles. I think this was a fear in the recent past but in the last 10 years in the UK there has been a strong drive to redefine professionalism and the role of the doctor for the 21^st century and it is central now to modern undergraduate and post graduate training with the importance of Consultants and GPs taking leadership roles in planning health care delivery.
 
Which scientific paper/publication has influenced you the most?
Huxley AF 1957 A theory of muscular contraction” Prog. In Biophys. And Biophys. Chem; 7:255.
Professor Sir Andrew Huxley was awarded the Nobel prize in medicine in 1963 with AL Hodgkin for nerve conduction but my personal memory is in muscle physiology (as one of my tutors) for his work on the theory of muscle contraction and the role of cross bridges. His clarity of thought was demonstrated in his ability to always ask the question everyone else wished they had asked! He was a kind and gentle teacher that gave time even for a simple medical student.
 
What single area of medical research in your speciality should be given priority?
The brain is the forgotten organ in multiple organ failure. We now recognize that acute brain dysfunction is a serious problem but we know little about its pathology, how to prevent it or recover from it.
 
What is the most challenging area in your speciality that needs further development?
There has been a rush towards ill conceived large scale pragmatic clinical effectiveness studies of various therapies few of which have shown much to change practice. Rather there is a need for more detailed scientific research to better define efficacy of therapies by exploring the pathological processes and the genetic and environmental influences of common disorders that result in multiple organ failure.
 
Which changes would substantially improve the quality of healthcare in your country?
Addressing the challenge of an ageing population and in particular the community medical and non-medical support of the aged infirm so that modern medicine does not grind to a halt.
 
Do you think doctors can make a valuable contribution to healthcare management? If so how?
By showing leadership and making the changes happen and not leaving it to others perhaps less informed to direct change.
 
How has the political environment affected your work?
I have tried to ignore it as much as possible. Politics is a business best left to politicians while the rest of the world gets on with life.
 
What are your interests outside of work?  
I treasure my family, a marriage of 28 years, with two undergraduates in medicine and one in architecture and doing all the jobs they ask of a father. When not escaping to the south of France or walking I become a generalist handyman so it can be a gardener, electrician, plumber, decorator, carpenter, car mechanic………and the Sunday Roast!
 
If you were not a doctor, what would you do?
With the exception of playing a musical instrument anything that combines academia, teaching and its practical application, but with preference in the natural world.

Background:

Loss of a limb for any a reason is a major event with profound implications on the psychological health of an individual involved. It has been seen that 20-60% of the amputees attending surgical or rehabilitation clinics are assessed as being clinically depressed^1-3. Individuals suffering traumatic limb loss at any age are likely to suffer subsequent difficulties with their body image, but these relationships are more striking in the younger age groups who have experienced traumatic injuries. The psychological reactions to amputation are clearly diverse and range from severe disability at one extreme; determined and effective resumption of a full and active life at other end. Indeed, among adults the age at which an individual receives the amputation is also an important factor. The investigation of psycho-social adaptation to amputation has generated a plethora of clinical and empirical studies ^4-7. An amputation is typically equated with loss of once perception of wholeness ⁸, loss of spouse ⁹, symbolic castration and even death ^{10, 11}. The individual’s response to a traumatic event is influenced by personality traits, psychiatric premorbid state, gender, peri-traumatic dissociation, prolonged disability of traumatic events, lack of social support and inadequate coping strategies ^12-15. Even though the previous research on consequences of amputation has focused primarily on relationships among demographic variables, coping mechanisms, and outcome measures; there is lack of literature on prevalence of various specific psychiatric disorders post-amputation ^{16, 17}. Most of the literature and research on prevalence of specific psychiatric morbidity has largely focused on symptoms of depression¹⁸.

1. To study various socio-demographic variables of amputees.
2. To find prevalence of psychiatric disorders in amputees from the out-patient population of the bones and joint surgery hospital, Srinagar which also has an artificial limb rehabilitation centre attached with it.

1. Informed consent from the patients under study
2. Amputation of more than one year duration
3. Age more than 14 years and less than 60 years
4. Patients were included in the study irrespective of their sex

1. Those who do not give consent
2. Those persons who have history of any DSM-IV axis I or axis II disorder before the development of amputation.
3. Presence of disabling medical or neurological conditions like motor neuron disease, Parkinson disease, etc.
4. Age less than 14 years
5. Age more than 60 years

Introduction

Currently, peripheral vascular disease (PVD), causing an inadequate oxygen supply to the limbs, globally affects no less than 3–10% of the population¹. Peripheral vascular disease, including diabetic foot, arteriosclerosis obliterans, and thromboangitis obliterans, commonly affect the arteries supplying the leg. Based on the severity of the symptoms, usually two clinical presentations are distinguished: intermittent claudication (IC) is characterised by pain upon walking while critical limb ischaemia (CLI) is a more severe form in which pain occurs at rest and which is accompanied by necrosis and ulceration.

Although several clinical studies show promising results, larger randomised, blinded, placebo-controlled trials are needed to provide definite proof of the clinical effects of adult stem cell therapy in these patients. In addition, questions regarding the cell population(s) to be used, optimal dose, and routes of administration will have to be addressed. If doctors and scientists can establish safe protocols for stem cell use, everyone can benefit from the full potential of the remarkable and possibly life-saving stem cell therapies.

Introduction

The legal high ‘Ivory Wave’, also known as ‘Ivory Coast’, ‘Purple Wave’ or ‘Vanilla Sky’, is a designer drug that has become popular among clubbers in the United Kingdom (UK) after mephedrone was banned in April 2010.¹ Ivory Wave is advertised as a relaxing bath salt and has been freely available on the Internet for about £15 a packet (200mg).² Three different versions have been on the market, namely, Ivory Wave, Ivory Wave Ultra (also known as Ivory Wave 2), and Ivory Wave 3, although their differences are unknown.³ Studies have shown that Ivory Wave contains cathinone-derived stimulants and, when snorted in high doses, bring similar effects to those of amphetamine and ecstasy.⁴ 

Introduction 

‘On the job training’- what does that mean?