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.

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.

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.

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.

Sex hormone status and bone metabolism in men with Crohn's disease.

BACKGROUND: Men with Crohn's disease (CD) are at risk of osteoporosis, but the factors contributing to low bone mineral density and its optimum treatment have not been established. AIM: To investigate the sex hormone status of men with CD, and to establish the influence of sex hormones on their bone metabolism. METHODS: Bone density was measured by dual energy X-ray absorptiometry at the hip and lumbar spine in 48 men with CD. Total serum testosterone and gonadotrophins were measured in all subjects and the free androgen index calculated in men with low or borderline total testosterone. Serum osteocalcin, pro-collagen carboxy-terminal peptide, bone specific alkaline phosphatase and urinary deoxypyridinoline were measured as markers of bone turnover. RESULTS: Eight (17%) men had osteoporosis, and a further 14 (29%) had osteopenia. Three (6%) men had a low free androgen index and normal gonadotrophins consistent with secondary hypogonadism, two of whom had osteopenia of the hip and spine. Age (P = 0.002) and small bowel Crohn's disease (P = 0.02) were the only independent predictors of serum testosterone. There was a significant association between total testosterone and osteocalcin (r = 0.53, 95%, CI: 0.29-0.71, P = 0.0001) which was independent of age and current steroid use (P = 0.0001). CONCLUSIONS: Previously undiagnosed hypogonadism is an uncommon cause of low bone density in men with CD. The independent association between testosterone and the bone formation marker osteocalcin suggests sex hormone status influences bone metabolism in men with CD. The results suggest testosterone replacement might be effective treatment for some men with osteoporosis and Crohn's disease.

Increased bone resorption in patients with Crohn's disease.

BACKGROUND: Patients with Crohn's disease are at risk of osteoporosis and premature fracture. However, the pathophysiology underlying bone loss remains poorly understood and the optimum treatment has not been established. AIM: To investigate mechanisms of bone loss in Crohn's disease using biochemical markers of bone turnover. METHODS: Bone mineral density was measured at the hip and spine using dual-energy X-ray absorptiometry in 117 patients (48 male) with Crohn's disease. Bone turnover was assessed by measuring serum osteocalcin (BGP), pro-collagen carboxy-terminal propeptide (PICP), bone specific alkaline phosphatase (BALP) and urinary deoxypyridinoline (DPD); and compared to age-matched healthy controls (n = 28). RESULTS: Bone mineral density was reduced (z-score < -1) in 48 (41%) patients with Crohn's disease. Mean values for bone formation markers in patients with Crohn's disease were all within the normal reference range (BGP 8.92 (+/- 3.23) ng/mL (normal range 3.4-10.0), BALP 17.6 (+/- 12.6) U/L (normal range 11.6-43.3), PICP 95.1 (+/- 46.5) ng/mL (normal range 69-163)) and were not significantly different to the control population. However, mean urinary DPD was significantly higher in patients with Crohn's disease compared to healthy controls (10.97 (+/- 9.22) nM DPD/mM creatinine vs. 5.02 (+/- 1.03) nM DPD/mM creatinine, difference in means = 5.95, 95% CI: -9.6 to -2.3, P = 0.00001) and compared to the UK reference range DPD levels were increased in 74 (63%) patients. CONCLUSIONS: Bone resorption as evidenced by urinary DPD was frequently increased in patients with Crohn's disease and was significantly higher than in an age-matched control population. The high levels of urinary DPD suggest increased bone collagen degradation may contribute to osteoporosis in patients with Crohn's disease. These results suggest anti-resorptive agents such as the bisphosphonates may be effective treatment for osteoporosis in Crohn's disease.

The effect of rectally administered steroids on bone turnover: a comparative study.

BACKGROUND: Oral glucocorticoids contribute significantly to the risk of osteoporosis in patients with inflammatory bowel disease. Less well established are the effects of rectally administered steroids on bone metabolism. AIM: To investigate the effects of two widely used rectal foam preparations (prednisolone metasulphobenzoate and hydrocortisone acetate) on biochemical markers of bone turnover. METHODS: Twenty-four patients with active inflammatory bowel disease randomly received a standard course of either prednisolone metasulphobenzoate or hydrocortisone acetate for 2 weeks. Biochemical markers of bone turnover were measured before, during and after treatment. Bone formation markers measured were serum osteocalcin (BGP) and bone-specific alkaline phosphatase (BALP). Urinary deoxypyridinoline (DPD) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 3.4, 95% CI: 2.0-4.8, P < 0.0001) and were similar in both hydrocortisone and prednisolone-treated groups. There was no significant reduction in BALP or BGP during treatment with either steroid preparation, and urinary DPD did not change significantly during treatment. CONCLUSIONS: During a 2-week course of rectal hydrocortisone acetate or prednisolone metasulphobenzoate, there was no significant change in biochemical markers of bone formation or resorption. These results suggest that pharmacological doses of rectal steroid foam preparations do not significantly impair bone turnover in patients with inflammatory bowel disease.

Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced. AIM: To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel. METHODS: The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks. RESULTS: Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores. CONCLUSIONS: Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.

Preliminary report of an association between measles virus and achalasia.

Complement fixation tests were performed on sera from 18 patients with achalasia and 12 age- and sex-matched controls against a number of bacterial and viral agents in an attempt to ascertain any association with previous infection or any evidence of an altered immune response. There was a statistically significant increase of antibody titre against measles virus in the sera of 21 patients with achalasia compared with age- and sex-matched controls and this was confirmed by haemagglutination inhibition.

Agglutinins to anaerobic bacteria in Crohn's disease and in Indian patients with diarrhoea.

Agglutinins to certain species of Eubacterium and Peptostreptococcus have been reported in sera from a high proportion of patients with Crohn's disease. Because this might be a non-specific finding common to patients with diarrhoea associated with damaged intestinal mucosa, we have compared the incidence of such agglutinins in patients with Crohn's disease with that seen in patients in North-East India with acute or chronic diarrhoea. The incidence of agglutinins in Crohn's disease was 44%, compared with 11% in acute and 17% in chronic diarrhoea. These figures suggest that mucosal damage alone does not explain the high incidence of agglutinins in Crohn's disease.