Leicester General Hospital

Objectives To describe new WHO 2020 guidelines on physical activity and sedentary behaviour. Methods The guidelines were developed in accordance with WHO protocols. An expert Guideline Development Group reviewed evidence to assess associations between physical activity and sedentary behaviour for an agreed set of health outcomes and population groups. The assessment used and systematically updated recent relevant systematic reviews; new primary reviews addressed additional health outcomes or subpopulations. Results The new guidelines address children, adolescents, adults, older adults and include new specific recommendations for pregnant and postpartum women and people living with chronic conditions or disability. All adults should undertake 150–300 min of moderate-intensity, or 75–150 min of vigorous-intensity physical activity, or some equivalent combination of moderate-intensity and vigorous-intensity aerobic physical activity, per week. Among children and adolescents, an average of 60 min/day of moderate-to-vigorous intensity aerobic physical activity across the week provides health benefits. The guidelines recommend regular muscle-strengthening activity for all age groups. Additionally, reducing sedentary behaviours is recommended across all age groups and abilities, although evidence was insufficient to quantify a sedentary behaviour threshold. Conclusion These 2020 WHO guidelines update previous WHO recommendations released in 2010. They reaffirm messages that some physical activity is better than none, that more physical activity is better for optimal health outcomes and provide a new recommendation on reducing sedentary behaviours. These guidelines highlight the importance of regularly undertaking both aerobic and muscle strengthening activities and for the first time, there are specific recommendations for specific populations including for pregnant and postpartum women and people living with chronic conditions or disability. These guidelines should be used to inform national health policies aligned with the WHO Global Action Plan on Physical Activity 2018–2030 and to strengthen surveillance systems that track progress towards national and global targets.

The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the prior position statements, published in 2012 and 2015, on the management of type 2 diabetes in adults. A systematic evaluation of the literature since 2014 informed new recommendations. These include additional focus on lifestyle management and diabetes self-management education and support. For those with obesity, efforts targeting weight loss, including lifestyle, medication, and surgical interventions, are recommended. With regards to medication management, for patients with clinical cardiovascular disease, a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist with proven cardiovascular benefit is recommended. For patients with chronic kidney disease or clinical heart failure and atherosclerotic cardiovascular disease, an SGLT2 inhibitor with proven benefit is recommended. GLP-1 receptor agonists are generally recommended as the first injectable medication.

BACKGROUND AND AIMS: Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS: A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS: The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2-4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). CONCLUSIONS: Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.

CONTEXT: Morbidity and mortality rates in patients with eating disorders are thought to be high, but exact rates remain to be clarified. OBJECTIVE: To systematically compile and analyze the mortality rates in individuals with anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS). DATA SOURCES: A systematic literature search, appraisal, and meta-analysis were conducted of the MEDLINE/PubMed, PsycINFO, and Embase databases and 4 full-text collections (ie, ScienceDirect, Ingenta Select, Ovid, and Wiley-Blackwell Interscience). STUDY SELECTION: English-language, peer-reviewed articles published between January 1, 1966, and September 30, 2010, that reported mortality rates in patients with eating disorders. DATA EXTRACTION: Primary data were extracted as raw numbers or confidence intervals and corrected for years of observation and sample size (ie, person-years of observation). Weighted proportion meta-analysis was used to adjust for study size using the DerSimonian-Laird model to allow for heterogeneity inclusion in the analysis. DATA SYNTHESIS: From 143 potentially relevant articles, we found 36 quantitative studies with sufficient data for extraction. The studies reported outcomes of AN during 166 642 person-years, BN during 32 798 person-years, and EDNOS during 22 644 person-years. The weighted mortality rates (ie, deaths per 1000 person-years) were 5.1 for AN, 1.7 for BN, and 3.3 for EDNOS. The standardized mortality ratios were 5.86 for AN, 1.93 for BN, and 1.92 for EDNOS. One in 5 individuals with AN who died had committed suicide. CONCLUSIONS: Individuals with eating disorders have significantly elevated mortality rates, with the highest rates occurring in those with AN. The mortality rates for BN and EDNOS are similar. The study found age at assessment to be a significant predictor of mortality for patients with AN. Further research is needed to identify predictors of mortality in patients with BN and EDNOS.

BACKGROUND: Conventional systematic review techniques have limitations when the aim of a review is to construct a critical analysis of a complex body of literature. This article offers a reflexive account of an attempt to conduct an interpretive review of the literature on access to healthcare by vulnerable groups in the UK METHODS: This project involved the development and use of the method of Critical Interpretive Synthesis (CIS). This approach is sensitised to the processes of conventional systematic review methodology and draws on recent advances in methods for interpretive synthesis. RESULTS: Many analyses of equity of access have rested on measures of utilisation of health services, but these are problematic both methodologically and conceptually. A more useful means of understanding access is offered by the synthetic construct of candidacy. Candidacy describes how people's eligibility for healthcare is determined between themselves and health services. It is a continually negotiated property of individuals, subject to multiple influences arising both from people and their social contexts and from macro-level influences on allocation of resources and configuration of services. Health services are continually constituting and seeking to define the appropriate objects of medical attention and intervention, while at the same time people are engaged in constituting and defining what they understand to be the appropriate objects of medical attention and intervention. Access represents a dynamic interplay between these simultaneous, iterative and mutually reinforcing processes. By attending to how vulnerabilities arise in relation to candidacy, the phenomenon of access can be better understood, and more appropriate recommendations made for policy, practice and future research. DISCUSSION: By innovating with existing methods for interpretive synthesis, it was possible to produce not only new methods for conducting what we have termed critical interpretive synthesis, but also a new theoretical conceptualisation of access to healthcare. This theoretical account of access is distinct from models already extant in the literature, and is the result of combining diverse constructs and evidence into a coherent whole. Both the method and the model should be evaluated in other contexts.

BACKGROUND: Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs has been estimated for the Global Burden of Disease Study 2010 (GBD 2010). The aims of this study were to develop global and regional prevalence models and estimate the global burden of disease of ASDs. METHOD: A systematic review was conducted for epidemiological data (prevalence, incidence, remission and mortality risk) of autistic disorder and other ASDs. Data were pooled using a Bayesian meta-regression approach while adjusting for between-study variance to derive prevalence models. Burden was calculated in terms of years lived with disability (YLDs) and disability-adjusted life-years (DALYs), which are reported here by world region for 1990 and 2010. RESULTS: In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons. After accounting for methodological variations, there was no clear evidence of a change in prevalence for autistic disorder or other ASDs between 1990 and 2010. Worldwide, there was little regional variation in the prevalence of ASDs. Globally, autistic disorders accounted for more than 58 DALYs per 100 000 population and other ASDs accounted for 53 DALYs per 100 000. CONCLUSIONS: ASDs account for substantial health loss across the lifespan. Understanding the burden of ASDs is essential for effective policy making. An accurate epidemiological description of ASDs is needed to inform public health policy and to plan for education, housing and financial support services.

BACKGROUND: Asthma and eosinophilic bronchitis are characterized by similar inflammatory infiltrates in the submucosa of the lower airway. However, eosinophilic bronchitis differs from asthma in that there is no variable airflow obstruction or airway hyperresponsiveness in the former condition. We tested the hypothesis that there were differences between the two conditions in the microlocalization of mast cells within the airway smooth muscle. METHODS: Immunohistochemical analysis of bronchial-biopsy specimens was completed in 17 subjects with asthma, 13 subjects with eosinophilic bronchitis, and 11 normal controls recruited from two centers. RESULTS: Both groups with disease had a similar degree of submucosal eosinophilia and thickening of the basement membrane and lamina reticularis. By contrast, the number of tryptase-positive mast cells in the bundles of airway smooth muscle from subjects with asthma (median, 5.1 mast cells per square millimeter of smooth muscle [range, 0 to 33.3]) was substantially higher than that in subjects with eosinophilic bronchitis (median, 0 mast cells per square millimeter; range, 0 to 4.8) and that in normal controls (median, 0 mast cells per square millimeter [range, 0 to 6.4]; P<0.001 for the comparison among the three groups). T cells and eosinophils were not usually seen in the airway smooth muscle in any of the groups. CONCLUSIONS: The infiltration of airway smooth muscle by mast cells is associated with the disordered airway function found in asthma.

Importance: The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown. Objective: To compare continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly. Design, Setting, and Participants: Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes. Interventions: A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups. Main Outcomes and Measures: The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version [SF-36]). Results: Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 [SD, 12] years; 634 [79%] women; mean body weight, 107.2 kg [SD, 22.7 kg]), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 [95% CI, -16.0 to -13.5] percentage points; P < .001). Waist circumference (-9.7 cm [95% CI, -10.9 to -8.5 cm]), systolic blood pressure (-3.9 mm Hg [95% CI, -5.8 to -2.0 mm Hg]), and SF-36 physical functioning score (2.5 [95% CI, 1.6-3.3]) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%). Conclusions and Relevance: Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT03548987.

The American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: 1) the decision to treat high-risk individuals with a glucagon-like peptide 1 (GLP-1) receptor agonist or sodium–glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalization for heart failure (hHF), cardiovascular death, or chronic kidney disease (CKD) progression should be considered independently of baseline HbA1c or individualized HbA1c target; 2) GLP-1 receptor agonists can also be considered in patients with type 2 diabetes without established cardiovascular disease (CVD) but with the presence of specific indicators of high risk; and 3) SGLT2 inhibitors are recommended in patients with type 2 diabetes and heart failure, particularly those with heart failure with reduced ejection fraction, to reduce hHF, MACE, and CVD death, as well as in patients with type 2 diabetes with CKD (estimated glomerular filtration rate 30 to ≤60 mL min–1 [1.73 m]–2 or urinary albumin-to-creatinine ratio &amp;gt;30 mg/g, particularly &amp;gt;300 mg/g) to prevent the progression of CKD, hHF, MACE, and cardiovascular death.

Abstract Objective To estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls. Design Systematic review and meta-analysis. Data sources Medline and Embase between January 2000 and December 2019, studies published in English and conducted on humans. Eligibility criteria for selecting studies Observational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group. Results This meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I 2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, P&lt;0.001). In populations of women with previous GDM, the cumulative incidence of T2DM was 16.46% (95% confidence interval 16.16% to 16.77%) in women of mixed ethnicity, 15.58% (13.30% to 17.86%) in a predominantly non-white population, and 9.91% (9.39% to 10.42%) in a white population. These differences were not statistically significant between subgroups (white v mixed populations, P=0.26; white v non-white populations, P=0.54). Meta-regression analyses showed that the study effect size was not significantly associated with mean study age, body mass index, publication year, and length of follow-up. Conclusions Women with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy. Systematic review registration PROSPERO CRD42019123079.

Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective: To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions: Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main Outcomes and Measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. Conclusions and Relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03611582.

The Tampa Scale for Kinesiophobia (TSK) is one of the most frequently employed measures for assessing pain-related fear in back pain patients. Despite its widespread use, there is relatively little data to support the psychometric properties of the English version of this scale. This study investigated the psychometric properties of the English version of the TSK in a sample of chronic low back pain patients. Item analysis revealed that four items possessed low item total correlations (4, 8, 12, 16) and four items had response trends that deviated from a pattern of normal distribution (4, 9, 12, 14). Consequently, we tested the psychometric properties of a shorter version of the TSK (TSK-11), having excluded the six psychometrically poor items. The psychometric properties of this measure were compared to those of the original TSK. Both measures demonstrated good internal consistency (TSK: alpha=0.76; TSK-11: alpha=0.79), test-retest reliability (TSK: ICC=0.82, SEM=3.16; TSK-11: ICC=0.81, SEM=2.54), responsiveness (TSK: SRM=-1.19; TSK-11: SRM=-1.11), concurrent validity and predictive validity. In respect of specific cut-off scores, a reduction of at least four points on both measures maximised the likelihood of correctly identifying an important reduction in fear of movement. Overall, the TSK-11 possessed similar psychometric properties to the original TSK and offered the advantage of brevity. Further research is warranted to investigate the utility of the new instrument and the cut-off scores in a wider group of chronic pain patients in different clinical settings.

Real-world studies have become increasingly important in providing evidence of treatment effectiveness in clinical practice. While randomized clinical trials (RCTs) are the "gold standard" for evaluating the safety and efficacy of new therapeutic agents, necessarily strict inclusion and exclusion criteria mean that trial populations are often not representative of the patient populations encountered in clinical practice. Real-world studies may use information from electronic health and claims databases, which provide large datasets from diverse patient populations, and/or may be observational, collecting prospective or retrospective data over a long period of time. They can therefore provide information on the long-term safety, particularly pertaining to rare events, and effectiveness of drugs in large heterogeneous populations, as well as information on utilization patterns and health and economic outcomes. This review focuses on how evidence from real-world studies can be utilized to complement data from RCTs to gain a more complete picture of the advantages and disadvantages of medications as they are used in practice.Funding: Sanofi US, Inc.

Abstract These guidelines for the management of patients up to 18 years with Langerhans cell histiocytosis (LCH) have been set up by a group of experts involved in the Euro Histio Net project who participated in national or international studies and in peer reviewed publications. Existing guidelines were reviewed and changed where new evidence was available in the literature up to 2012. Data and publications have been ranked according to evidence based medicine and when there was a lack of published data, consensus between experts was sought. Guidelines for diagnosis, initial clinical work‐up, and treatment and long‐term follow‐up of LCH patients are presented. Pediatr Blood Cancer 2013;60:175–184. © 2012 The Authors. Pediatric Blood &amp; Cancer , published by Wiley Periodicals, Inc.

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.

National Clinical Guidelines for Stroke. Intercollegiate Working Party for Stroke, Royal College of Physicians. (Pp 150; £15.95.) Lavenham Press, 2000. ISBN 1-86016-120-0.\***| Stroke is a common problem, being the third cause of mortality in the UK and the leading cause of adult disability with a resultant significant cost burden to the NHS and social services. The guidelines highlight the wide national variation in the implementation of evidence based practice as seen in the Stroke Association's National Survey and the Royal College of Physicians …

OBJECTIVE: To determine time to treatment intensification in people with type 2 diabetes treated with one, two, or three oral antidiabetes drugs (OADs) and associated levels of glycemic control. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study based on 81,573 people with type 2 diabetes in the U.K. Clinical Practice Research Datalink between January 2004 and December 2006, with follow-up until April 2011. RESULTS: In people with HbA1c ≥7.0, ≥7.5, or ≥8.0% (≥53, ≥58, or ≥64 mmol/mol), median time from above HbA1c cutoff to intensification with an additional OAD was 2.9, 1.9, or 1.6 years, respectively, for those taking one OAD and >7.2, >7.2, and >6.9 years for those taking two OADs. Median time to intensification with insulin was >7.1, >6.1, or 6.0 years for those taking one, two, or three OADs. Mean HbA1c at intensification with an OAD or insulin for people taking one, two, or three OADs was 8.7, 9.1, and 9.7%. In patients taking one, two, or three OADs, median time from treatment initiation to intensification with an OAD or insulin exceeded the maximum follow-up time of 7.2 years. The probability of patients with poor glycemic control taking one, two, or three OADs, intensifying at end of follow-up with an OAD, was 21.1-43.6% and with insulin 5.1-12.0%. CONCLUSIONS: There are delays in treatment intensification in people with type 2 diabetes despite suboptimal glycemic control. A substantial proportion of people remain in poor glycemic control for several years before intensification with OADs and insulin.

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 &lt; 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 &lt; 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.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general. METHODS: We included patients aged over 60 years undergoing major non-cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters. RESULTS: At 7 days, POCD was found in 37/188 patients (19.7%, [14.3-26.1%]) after general anaesthesia and in 22/176 (12.5%, [8.0-18.3%]) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5-20.4%]) after general anaesthesia vs. 23/165 (13.9%, [9.0-20.2%]) after regional anaesthesia, P = 0.93. The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%[15.0-28.4%]) vs. 20/158 (12.7%[7.9-18.9%]) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P < 0.05)). CONCLUSION: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long-term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery.

Postoperative cognitive function (POCD) has been subject to extensive research. In the literature, large differences are apparent in methodology such as the test batteries, the interval between sessions, the endpoints to be analysed, statistical methods, and how neuropsychological deficits are defined. Traditionally, intelligence tests or tests developed for clinical neuropsychology have been used. The tests for detecting POCD should be based on well-described sensitivity and suitability in relation to surgical patients. In tests using scores, floor/ceiling effects may compromise the evaluation if the tests are either too easy or to difficult. Uncontrolled testing facilities and change of test personnel may affect the test performance. Practice effects are pronounced in neuropsychological tests but have generally been ignored. The use of a suitable normative population is essential to allow correction for practice effects and variability between sessions. Missing follow-up may severely compromise valid conclusions since subjects unable or unwilling to be examined are particularly prone to suffer from POCD. In the statistical analysis of the test results, the evaluation should be based on differences between pre- and postoperative performance. Parametric statistical tests are not relevant unless the appropriate Gaussian distributions are present, perhaps after transformation of data. The definition of cognitive dysfunction should be restrictive and the criteria should be fulfilled in only a small proportion of volunteers. In the literature, these requirements often have not been fulfilled. This precludes a reasonable estimation of the incidence of POCD and the conclusions of comparative studies should be interpreted with great caution. In this review article, we present a number of recommendations for the design and execution of studies within this area. In addition, the critical reader may use these recommendations in the evaluation of the literature.