Apparent discrimination in the provision of biologic therapy to patients with Crohn's disease according to ethnicity.

OBJECTIVES: The objective of the study was to investigate whether patients from a South Asian ethnic background who had Crohn's disease received equivalent access to therapy with biologics compared to patients with an English background. STUDY DESIGN: The study was retrospective and covered the period 2008 to 2012. It was based on a register of all patients with Crohn's disease in Leicestershire who are treated with biologics. The prevalence of Crohn's disease in Leicestershire amongst South Asian and English patients was known from earlier studies and from these data it was possible to make corrections to allow for the difference in frequency of the condition between the two communities. METHODS: All adult patients who received biologics for treatment of Crohn's disease in Leicestershire between 2008 and 2012 were reviewed and their gender and ethnicity noted as well as whether they had received infliximab or adalumimab. The expected numbers of patients who should have received these therapies were calculated in two ways: RESULTS: One hundred and twenty six patients with Crohn's disease who received treatment with biologics were European and 13 South Asian. The patients' gender was also noted and 67 European patients (53%) were female as were six Asians (46%). Based on prevalence data, the expected distribution of the treatment would have been for 97 of the patients to have been European and 42 to have been South Asian. If 126 European patients warranted treatment, on this basis the expected number of South Asian patients in need of biologic therapy would have been 55. Based on the smaller predicted number of South Asian patients (42) the difference is significant at P < 0.0001 [Proportion difference=0.69 (95% confidence interval=0.539278-0.809576]. For the difference to be extinguished the number of English patients who should have received biologic therapy would have been as low as between 30 and 39 cases (based on the calculated proportion of 97 and the actual figure of 126 European patients respectively). Based on a population composition, rather than prevalence data, in which 24% of the Leicester community should have been of South Asian origin, 33 patients would have received biologics compared with 92 patients of English origin (66%). This is significantly different to the 13 patients who did receive treatment (z=-3.2, P < 0.001). CONCLUSIONS: Suggested reasons for these differences have included concerns about the animal origins of infliximab as well as difficulties associated with accessing the service, such as the provision of information in an appropriate language through appropriate media. For those who come from groups with significant social deprivation there is often a readiness to accept more limited clinical services. However, such differences themselves, are examples of discrimination in clinical practice.

Microscopic colitis: a review.

AIM: In recent years, microscopic colitis has been increasingly diagnosed. This review was carried out to evaluate demographic factors for microscopic colitis and to perform a systematic assessment of available treatment options. METHOD: Relevant publications up to December 2013 were identified following searches of PubMed and Google Scholar using the key words 'microscopic colitis', 'collagenous colitis' and 'lymphocytic colitis'. Two-hundred and forty-eight articles were identified. RESULTS: The term microscopic colitis includes lymphocytic colitis and collagenous colitis. Both have common clinical symptoms but are well defined histopathologically. The clinical course is usually benign, but serious complications, including death, may occur. A peak incidence from 60 to 70 years of age with a female preponderance is observed. Although most cases are idiopathic, associations with autoimmune disorders, such as coeliac disease and hypothyroidism, as well as with exposure to nonsteroidal anti-inflammatory drugs and proton-pump inhibitors, have been observed. The incidence and prevalence of microscopic colitis is rising and good-quality epidemiological research is needed. Treatment is currently largely based on anecdotal evidence and on results from limited clinical trials of budesonide. Long-term follow-up of these patients is not well established. CONCLUSION: The review synthesizes work on the definition of microscopic colitis and the relationship between collagenous and lymphocytic colitis. It reviews the international epidemiology and work on aetiology. In addition, it critically considers the efficacy of a range of treatments.

The development of medical education in Eastern Europe during the 20th century and the emergence of 'English parallel' courses.

This paper will explore the development of medical education in the Soviet Union, its underlying principles and the subsequent migration of this format into the countries of the Soviet Bloc following World War II. The impact of Perestroika and the collapse of the Warsaw Pact on university training and medical education in particular will be reviewed. The need for external funding as a factor in the emergence of English Parallel courses in Hungary, Czechoslovakia and subsequently in other countries will also be considered.

Khan v Meadows [2021] UKSC 21 and its potential impact on clinical negligence cases.

Khan v Meadows, which was decided recently by the Supreme Court, will have a profound effect on day-to-day clinical practice and future clinical negligence cases. It has clarified the scope of duty of care and to a significant extent links it to the questions being asked by patients of their doctors and by doctors of their colleagues. Will courts now consider that when a patient consults a doctor, he or she is seeking an answer to a specific question or a more general question hidden within that specific question? Clearly the onus will be on clinicians to define exactly what is wanted by the patient or by a colleague.

NHS Trust Boards and Health and Well-being Boards: Do they play any role in the management of disparate levels of care for South Asian patients with Inflammatory Bowel Disease?

Aims: There is evidence of disparate levels of care for members of ethnic minority communities with inflammatory bowel disease in various NHS Trusts and Health Boards in England and Scotland. The purpose of this study was to investigate whether there was any association between the existence of disparate levels of care and the ethnic composition of the management boards of NHS Trusts and Health Boards. It also examined the ethnic composition of Health and Wellbeing Boards associated with these Trusts in England. Method: NHS Trusts in England and Health Boards in Scotland, which had been involved in previous studies of disparate levels of care, were identified through a review of the relevant published papers. Health and Wellbeing Boards associated with these Trusts were then identified. Executive and non-executive membership of the NHS Trust, Health Boards and Health and Wellbeing Boards was determined through scrutiny of their web pages. Results: The proportion of Asians, who were executive officers, was significantly lower than the proportion who were non-executive board members both for trusts who offered disparate care (z = 2.22; p < 0.03) and those which did not (z = 2.24; p < 0.03). There was no significant difference in the proportion of Asians who were non-executive board members between the two types of trust. The proportion of ethnic minority members of English Health and Well-Being Boards, where there was evidence of disparate levels of care received by South Asian patients was significantly greater than on Boards where this was not the case. (z = 2.8. p < 0.005). Conclusions: The relation of these findings to disparate levels of care is unclear. However, it may point to a culture of tokenism, where either the members are not truly representative of underserved communities or they are unable to have any influence on local policy decisions. In either case there is an urgent need to develop better links with minority communities who are underserved so that issues can be effectively identified and remedied.

Randomized clinical trial of metronidazole ointment versus placebo in perianal Crohn's disease.

BACKGROUND: The potential for metronidazole 10 per cent ointment to exert therapeutic benefit in perianal Crohn's disease, while minimizing the adverse effects found with oral metronidazole, was evaluated in a randomized placebo-controlled study. METHODS: Subjects with perianal Crohn's disease were randomized to metronidazole 10 per cent ointment, 0.7 g applied perianally three times daily, or placebo ointment. The Perianal Crohn's Disease Activity Index (PCDAI) was scored at baseline and after 4 weeks of treatment. Perianal pain was assessed on a visual analogue scale. RESULTS: Seventy-four subjects (33 metronidazole, 41 placebo) were evaluated. The mean(s.e.m.) reduction in PCDAI score at 4 weeks was 2.4(0.5) in the metronidazole group and 2.2(0.4) in the placebo group (P = 0.660). More subjects in the metronidazole group than the placebo group showed a reduction in PCDAI score of at least 5 points (10 of 27 versus 4 of 34; P = 0.031). Perianal discharge was reduced significantly in metronidazole-treated subjects (P = 0.012). A greater reduction in perianal pain was seen in the metronidazole group, which approached statistical significance (P = 0.059). No serious adverse events were reported. CONCLUSION: Metronidazole 10 per cent ointment was not effective in the reduction of PDCAI score, but some secondary outcomes showed improvement suggestive of a treatment effect. It is well tolerated, with minimal adverse effects, and has potential as treatment for pain and discharge associated with perianal Crohn's disease. REGISTRATION NUMBER: NCT00509639 (http://www.clinicaltrials.gov).

A re-appraisal of lactose intolerance.

BACKGROUND: Lactose, beta-galactose-1,4-glucose, is hydrolysed by the enzyme lactase. Lactose intolerance occurs when lactase deficiency causes clinical symptoms. AIMS: To provide an overview of lactose intolerance, including definition, aetiology and epidemiology, the clinical symptoms and diagnostic testing and management. METHODS: A literature review was carried out to meet the aims of this paper. This resulted in the analysis of a database of patients tested for lactose intolerance to provide examples of the consequences of problems of terminology identified. CONCLUSIONS: The terminology relating to lactose intolerance is confusing for clinicians and researchers. Clinicians need to ensure that these problematic terms do not cause diagnostic mistakes and inappropriate treatment. Researchers should be aware of inconsistent terminology in studies and resultant problems with the interpretation of results.

Meta-analysis: mortality in Crohn's disease.

AIM: To perform a meta-analysis is of published literature reporting standardized mortality ratios (SMR) for Crohn's patients from 1970 to date. METHODS: Medline search identified relevant papers. Exploding references identified additional papers. When two papers reviewed mortality of one patient group at different times, the later publication was used. RESULTS: Of 13 papers identified, three studies reported SMR below 1.0, two others had confidence intervals including 1.0. All other studies reported mortality higher than the general population. Meta-analysis using a random effects model shows the pooled estimate for SMR in Crohn's disease is 1.52 (95% CI: 1.32 to 1.74 [P < 0.0001]). Meta-regression shows the SMR for these patients has decreased slightly over the past 30 years, but this decrease is not statistically significant (P = 0.08). CONCLUSION: Assessing evidence from original studies and conducting a meta-analysis shows age-adjusted mortality risk from Crohn's disease is over 50% greater than the general population. Whilst mortality has improved since the condition was first recognized, further evaluation of the patients studied in the cohorts included here is necessary to assess more recent changes in clinical practice.

Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis.

BACKGROUND: The cancer risk of low-grade dysplasia (LGD) in chronic ulcerative colitis is variable and its management remain contentious. AIM: To determine the risk of cancer or any advanced lesion once LGD is diagnosed. METHODS: A MEDLINE, EMBASE and Pub Med search was conducted using the key words 'surveillance', 'colorectal cancer', 'low-grade dysplasia' and 'ulcerative colitis'. A random effects model of meta-analysis was used. RESULTS: Twenty surveillance studies had 508 flat LGD or LGD with dysplasia-associated lesion or mass. An average of 4.3 colonoscopies was performed/patient post-LGD diagnosis (range: 3-7.6). An average of 18 biopsies taken per colonoscopy (range: 9-24) detected 73 advanced lesions (cancer or high-grade dysplasia) pre-operatively. The cancer incidence was 14 of 1000 (95% CI: 5.0-34) person years duration (pyd) and the incidence of any advanced lesion was 30 of 1000 pyd (95% CI: 12-76). When LGD is detected on surveillance there is a ninefold risk of developing cancer (OR: 9.0, 95% CI: 4.0-20.5) and 12-fold risk of developing any advanced lesion (OR: 11.9, 95% CI: 5.2-27). CONCLUSIONS: The risk of developing cancer in patients with LGD is high. These estimates are valuable for decision-making when LGD is encountered on surveillance.

Long-term prognosis in Crohn's disease: An epidemiological study of patients diagnosed more than 20 years ago in Cardiff.

AIM: To investigate the incidence of death in patients diagnosed with Crohn's disease in Cardiff over 20 years ago. METHODS: The Cardiff database of patients with Crohn's disease contains data on all patients diagnosed there since 1934. Patients (394) diagnosed before 1 January 1985 were traced and their mortality status on 31 December 2004 was established. RESULTS: The overall standardized mortality ratio (SMR) was 1.29 (95% CI 1.12-1.45) and it has not significantly changed since the 1970s. SMR decreases with age, from 16.95 (95% CI 14.99-18.91) for patients aged 10-19 years (although only one death) to 0.92 (95% CI 0.65-1.19) in those over 75 years. Kaplan-Meier analysis of age at death shows that patients diagnosed aged 10-26 years have median age at death of 58 years, those aged 27-52 years of 66 years, those aged 53-58 years of 74 years, and those over 59 years of 79 years. CONCLUSIONS: It shows a significantly raised SMR, not statistically changed since the 1970s and similar to other chronic conditions. Patients diagnosed younger have worse prognosis than those diagnosed later in life and a reduced life expectancy compared with the general population.

Duration of treatment with 5-aminosalicylic acid compounds.

The development of 5-aminosalicylic acid (5-ASA) therapy as a life long treatment for ulcerative colitis is reviewed from its origins in the 1940s to the present day. The drug was designed to treat rheumatoid arthritis, but was found helpful in the management of nine patients with ulcerative colitis. This discovery preceded the emergence of the clinical trial as a tool for assessing a new drug's efficacy; as a result it lacked scientific rigour and was selective in its presentation of results. Nevertheless it identified the future cornerstone of therapy in ulcerative colitis. In 1962, the first double blind controlled trial of sulphasalazine was conducted on 40 patients. Outcome measures were subjective and included symptoms and an assessment of the rectal mucosa. In 1973, the first two papers on the role of sulphasalazine in maintenance of remission were published. Both used placebo controls and had a stratified design. Outcomes were measured using "an intention to treat" approach. The British study of 64 patients used both subjective and objective criteria to assess outcomes. Patients on placebo had a relapse rate four times patients on active treatment and this founded the basis for a life long approach to therapy with 5-ASA compounds in ulcerative colitis. However, in 1985, a small "on demand" study of 32 patients suggested this approach might be as effective as continuous treatment. Some support for this view came from an Italian study which showed no benefit to continued treatment for those in remission for two years or more. The central problem these studies identify is that of adherence to treatment in the long-term. Few studies have considered patients' attitudes to continuous therapy and it is an area that needs further investigation.

Views of specialist registrars on specialty care in the community: employment prospects and the need for additional training.

AIM: To obtain the views of specialist registrars on specialty care in the community. METHOD: Specialist registrars from five Deaneries in England completed an online questionnaire about their views on employment prospects, the role of specialty care in the community, and the need for additional training in this area. RESULTS: One hundred and twenty seven replies were received over a four week period. Thirty (24%) viewed their future employment prospects as consultants as poor or very worrying. Seventy seven (61%) specialist registrars considered that as consultants they will need to work directly in the community. Thirty nine of these (51%) considered the need to work close to patients directly in the community as either a "bad" or "very bad" development. However, 102 (80%) specialist registrars believed that they should receive training on the delivery of specialty care in the community and 96 (76%) wanted this in the form of a university based degree.

Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease.

BACKGROUND: Crohn's disease is associated with small bowel cancer whilst risk of colorectal cancer is less clear. AIM: To ascertain the combined estimates of relative risk of these cancers in Crohn's disease. METHODS: MEDLINE was searched to identify relevant papers. Exploding references identified additional publications. When two papers reviewed the same cohort, the later study was used. RESULTS: Meta-analysis showed overall colorectal cancer relative risk in Crohn's disease as 2.5 (1.3-4.7), 4.5 (1.3-14.9) for patients with colonic disease and 1.1 (0.8-1.5) in ileal disease. Meta-regression showed reduction in relative risk over the past 30 years. Subgroup analysis showed Scandinavia had significantly lower colorectal cancer relative risk than the UK and North America. Cumulative risk analysis showed 10 years following diagnosis of Crohn's disease relative risk of colorectal cancer is 2.9% (1.5%-5.3%). Meta-analysis showed small bowel cancer relative risk in Crohn's disease is 33.2 (15.9-60.9). Small bowel cancer relative risk has not significantly reduced over the last 30 years. CONCLUSION: Relative risk of colorectal and small bowel cancers are significantly raised in Crohn's disease. Cumulative risk of colorectal cancer of 2.9% at 10 years suggests a potential benefit from routine screening. However, the value of screening requires rigorous appraisal.

Long-term prognosis in Crohn's disease: factors that affect quality of life.

BACKGROUND: There are many studies investigating quality of life in recently diagnosed patients and following surgery for Crohn's disease, but there are none investigating quality of life changes with disease duration. The response shift model suggests quality of life improves with time following diagnosis. AIM: To assess how well the model applies to patients with Crohn's disease. METHODS: The Cardiff Crohn's disease database contains data on all patients diagnosed there since 1934. Three hundred and ninety four patients diagnosed before 1 January 1985 were traced and the mortality status on 31 December 2004 established. Two hundred and eleven still living were sent quality of life questionnaires. Two hundred and eighty five questionnaires were sent to patients with varying disease duration attending out-patient clinics in Leicester. RESULTS: Eighty-nine valid replies were received from Cardiff, 63 from Leicester patients diagnosed over 20 years, 69 from Leicester patients diagnosed <10 years. There was no difference in quality of life between newly diagnosed and established patients. Of greatest concern was possible need for ostomy, uncertain nature of disease, and lack of energy. Stepwise regression showed that increased disease severity, older age and smoking adversely affect quality of life. DISCUSSION: Quality of life is equally poor in patients with established disease as in those newly diagnosed, and directly correlates with disease severity. The response shift model may not be applicable in Crohn's disease.

Increased birth prevalence of cardiac defects in Yuma, Arizona.

A systematic study was undertaken to estimate the birth prevalence of congenital heart disease because there was a clinical impression that a disproportionate number of cases occurred in Yuma, Arizona. Control data were obtained from Sierra Vista, Arizona, a region with similar demographic characteristics, and from the Baltimore-Washington Infant Study. Patients with chromosomal or syndromal associations were excluded. In the Baltimore-Washington Infant Study only echocardiographic and invasively documented cases were included. From 1983 to 1988 the birth prevalence was significantly higher in Yuma (10.5/1,000) than in Sierra Vista (5.4/1,000, p less than 0.0001). As assessed only by invasive or echocardiographic diagnosis, there was a higher birth prevalence of congenital heart disease in the study population (6.7/1,000) compared with both the Baltimore-Washington Infant Study (3.7/1,000, p = 0.0008) and Sierra Vista (4.6/1,000, p = 0.04). Families were interviewed to exclude cases in which the mother did not spend the month before conception and the first trimester in Yuma or Sierra Vista. The birth prevalence for Yuma (6.0/1,000) remained significantly greater than that for Sierra Vista (3.8/1,000, p = 0.03). The exclusion of cases in which the mother resided elsewhere suggests, but does not prove, that an environmental influence may have played a role in the increased birth prevalence of congenital heart disease in this community.

Effects of selenium in vitro on human T-lymphocyte functions and K-562 tumor cell growth.

In vitro E-rosette formation, lymphocyte mitogenesis, and natural killer (NK) cell activity of human blood lymphocytes were strongly inhibited by high concentrations (10(-4) M) of sodium selenite, sodium selenate, and selenium dioxide. Lower concentrations (10(-5) or 10(-7) M) also inhibited E-rosette formation and natural killer cell activity against K-562 tumor cells. Lymphocyte transformation induced by concanavalin A (con A) or pokeweed mitogen (PWM) was also inhibited by all selenium compounds tested, but only at the highest concentrations (10(-5) and 10(-4) M). There was depression of the total number of viable lymphocytes following incubation with selenium dioxide only at a high concentration (10(-4) M). Interferon production was enhanced at lower levels (10(-9) to 10(-6)M) of selenium dioxide while a higher concentration (10(-5) and 10(-4)M) appeared to inhibit its production. The mechanism of inhibition by selenium compounds (10(-4) M) is due, in part, to the decrease of viable lymphocytes. It is unclear how other and lower concentrations (10(-7) or 10(-9) M) of selenium compounds inhibit E-rosette formation, NK activity, or K-562 tumor cell growth.

It is time to test low level laser therapy in Great Britain.

Low level laser therapy (LLLT) has been used in Eastern Europe and Asia for the treatment of a wide range of conditions for many years. Its continued acceptance in these populations reflects the efficacy with which it is regarded both by clinicians and their patients. Although there have been a substantial number of reports on its clinical benefit and some practitioners have used the technique in North America and Australasia it has yet to be subjected to detailed assessment through randomised clinical trials. The purpose of this review is to stimulate interest in the technique and to encourage rigorous research into its potential value.

Colorectal cancer prevention in ulcerative colitis: a case-control study.

BACKGROUND: The risk of colorectal cancer (CRC) in ulcerative colitis (UC) increases with extent and duration of disease. Identifying other risk factors would allow targeting of sub-groups at greatest risk, enabling more cost-effective surveillance. METHODS: We conducted a case-control study comparing 102 cases of CRC in UC with matched controls. Odds ratios (OR) for cancer risk were estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables. RESULTS: Regular 5-aminosalicylic acid (5-ASA) therapy reduces cancer risk by 75% (OR 0.25, 95% CI: 0.13-0.48, P < 0.00001). Adjusting for other variables, taking mesalazine regularly reduces risk by 81% (OR 0.19, 95% CI: 0.06-0.61, P=0.006) and visiting a hospital doctor more than twice a year also reduces risk (OR 0.16, 95% CI: 0.04-0.60, P=0.007). Considering variables independently, having a family history of sporadic CRC in any relative increases risk fivefold (OR 5.0, 95% CI: 1.10-22.82, P < 0.04). CONCLUSIONS: CRC risk among UC patients can be reduced by regular therapy with 5-ASA medication. Colonoscopic surveillance may be best targeted on those unable to take 5-ASAs (e.g. due to allergy) and those with a positive family history of CRC.

Rectal steroids suppress bone formation in patients with colitis.

BACKGROUND: The aetiology of bone loss in inflammatory bowel disease is multifactorial, but oral corticosteroids are an important contributory factor. Rectally administered steroids are widely used in patients with distal disease, but very little is known about their effect on bone metabolism. The aim of this study was to investigate the effect of a standard course of rectal prednisolone on biochemical markers of bone turnover. METHODS: In a longitudinal study of 10 patients, biochemical markers of bone turnover were measured before, during and after treatment with prednisolone metasulphobenzoate (Predfoam, Pharmax Ltd) 20 mg twice daily for 2 weeks. Bone formation markers measured were serum osteocalcin (BGP), bone-specific alkaline phosphatase (BALP) and procollagen carboxy-terminal propeptide (PICP). Urinary deoxypyridinoline (dPyr) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 2.3 (+/-13.1), 95% CI: 0.11-4.48, P = 0.04). There was a significant fall in BALP (P = 0.02) during treatment, and a rapid but non-significant fall in BGP (P = 0.19). PICP (0.42), and urinary dPyr (0.30) did not change significantly during treatment. CONCLUSIONS: Following a standard 2-week course of rectal prednisolone metasulphobenzoate, we observed a significant fall in bone-specific alkaline phosphatase activity. These results suggest that bone formation is suppressed in patients with distal colitis treated with pharmacological doses of rectal steroids.