Highly diastereoselective oxy-Michael additions of enantiopure δ-lactol anions to nitroalkenes: Asymmetric synthesis of 1,2-amino alcohols

The "naked" alkoxide 1 of (S)-6-methyl-δ-lactol acts as an excellent chiral hydroxide equivalent in highly diastereoselective oxy-Michael additions to nitroalkenes (see scheme). The excellent stereoinduction arises from what becomes a superb protecting group in the resulting 1,2-amino alcohol products. R1 = alkyl, aryl, furanyl, thiophenyl; R2,R 3 = -(CH2)3CHCH3O-

The time to inflammatory bowel disease diagnosis for patients presenting with abdominal symptoms in primary care and its association with emergency hospital admissions and surgery:a retrospective cohort study

Background: Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed to evaluate this and assess whether time to diagnosis is associated with clinical outcomes.Methods: A retrospective cohort study using English primary care data from 1st January 2010 to 31st December 2019 linked to hospital admission data was undertaken. Patients were followed from the first IBD related presentation in primary care to IBD diagnosis. Associations of time to diagnosis exceeding a year were assessed using a Robust Poisson regression model. Associations between time to diagnosis and IBD-related emergency hospital admissions and surgery were assessed using Poisson and Cox proportional hazards models respectively. Results: Of 28,092 IBD patients, 60% had ulcerative colitis (UC) and 40% had Crohn’s disease (CD). Median age was 43 years (interquartile range 30-58) and 51.9% were female. Median time to diagnosis was 15.6 months (IQR 4.3- 28.1). Factors associated with more than a year to diagnosis included: female sex (adjusted risk ratio 1.23, 95% CI 1.21-1.26), older age (1.05, 1.01-1.10, comparing &gt;70 years to 18-30), obesity (1.03, 1.00-1.06), smoking (1.05, 1.02-1.08), CD compared to UC (1.13, 1.11-1.16) and a faecal calprotectin over 500 μg/g (0.89(0.82-0.95)). The highest quartile of time to diagnosis compared to the lowest was associated with IBD-related emergency admissions (incidence rate ratio 1.06,1.01-1.11).Conclusion: Longer times to IBD diagnoses were associated with being female, advanced age, obesity, smoking, and Crohn’s disease. More IBD related emergency admissions were observed in patients with a prolonged time to diagnosis.<br/

Cardiovascular and Renal Morbidity in Takayasu Arteritis: A Population-Based Retrospective Cohort Study From the United Kingdom.

OBJECTIVE Cardiovascular disease (CVD) is a major complication and cause of mortality in Takayasu arteritis (TAK), but population-based controlled studies from the UK are lacking. We undertook the present study to investigate the frequency of morbidity and mortality related to CVD, as well as to cerebrovascular and kidney disease, among patients with TAK in the UK. METHODS Yearly cohort and cross-sectional studies were performed from 2000 to 2017 to estimate annual incidence and prevalence, respectively, of TAK. Using a UK primary care database (IQVIA Medical Research Data), an open retrospective matched cohort study was conducted to estimate risk of hypertension, diabetes, cardiovascular morbidity, chronic kidney disease (CKD), and all-cause mortality in TAK. Risk (adjusted hazard ratio [HR]) of the assessed comorbidities among patients with TAK compared to age- and sex-matched controls was estimated. Changes in medication prescription over time were examined in both groups. RESULTS One hundred forty-two patients with TAK (median age 53.4 years [interquartile range 33.8-70.7]) and 1,371 matched controls were included. The annual incidence and prevalence of TAK were 0.8 per million and 7.5 per million respectively. All-cause mortality was increased in TAK (adjusted HR 1.88 [95% confidence interval 1.29-2.76]). Patients with TAK had an increased risk of developing ischemic heart disease, stroke/transient ischemic attack, combined CVD, and peripheral vascular disease compared to controls, but no increase in risk of hypertension, CKD, heart failure, or diabetes. Only ~50% of patients with TAK requiring secondary CVD prevention were prescribed statins or antiplatelet agents within 1 year after study entry. CONCLUSION Cardiovascular morbidity was increased among patients with TAK receiving primary care services in the UK. Treatment with statins and antiplatelet agents in these patients was suboptimal

Allergic Diseases and Long Term Risk of Autoimmune Disorders: .

BACKGROUND The association between allergic diseases (ADs) and autoimmune disorders (AIDs) is not well established. OBJECTIVE To determine incidence rates of AIDs in allergic rhinitis/conjunctivitis (ARC), atopic eczema (AE) and asthma, and investigate for co-occurring patterns. METHODS : Retrospective cohort study (1990-2018) employing "The Health Improvement Network" (UK primary care database).: ARC, AE and asthma - all ages.: For each exposed patient, up to 2 randomly selected age- and gender-matched controls with no documented AD.Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters. RESULTS 782 320, 1 393 570 and 1 049 868 patients with ARC, AE and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), vitiligo, rheumatoid arthritis (RA), psoriasis, pernicious anaemia, inflammatory bowel disease (IBD), coeliac disease (CD) and autoimmune thyroid disease were uniformly higher in the 3 ADs compared to controls. Specifically, aIRRs of SLE (1.45) and SS (1.88) were higher in ARC; SLE (1.44), SS (1.61) and myasthenia (1.56) higher in asthma; SLE (1.86), SS (1.48), vitiligo (1.54) and psoriasis (2.41) higher in AE.There was no significant effect of the 3 ADs on multiple sclerosis and ARC and AE on myasthenia.ARM: ADs clustered with multiple AIDs. Three age- and gender-related clusters were identified, with relatively complex pattern in females ≥55 years. CONCLUSION The long-term risk of AIDs are significantly higher in patients with ADs. ADs and AIDs show age- and gender-related clustering patterns

Ethnicity-based differences in the incident risk of allergic diseases and autoimmune disorders: a UK-based retrospective cohort study of 4.4million participants.

The burden of allergic diseases (ADs) such as asthma and rhinitis and autoimmune disorders (AIDs) such as rheumatoid arthritis (RA) are relatively low/moderate in low and low-middle income countries and there is some evidence regarding higher incidence rates of these conditions amongst immigrant population settled in high income countries . The burden of ADs are particularly high in high income countries such as UK, Republic of Ireland and New Zealand . Studies in immigrants have been limited by several factors including relatively small sample size, shorter duration, and methodological issues such as selection bias, survey or questionnaire-based data, focus on a single or limited number of ADs or AIDs, and some not accounting for important disease confounders such as smoking history

The risk of later surgery at the anastomotic site following right hemicolectomy for Crohn's disease in a national cohort of 12 230 patients.

BACKGROUND Crohn's disease (CD) has a high-risk of bowel resection and later surgery for recurrent disease. Recent guidelines recommend colonoscopy 6-12 months following surgery to reduce further surgical intervention through medical therapy intensification. AIMS To investigate the risk of further surgery at the anastomosis following right hemicolectomy for CD. METHODS Hospital Episode Statistics were used to identify patients with CD and a right hemicolectomy between 2007 and 2016. Adherence to post-resection colonoscopy guidance timing and risk of further surgery at the anastomosis were examined. Cox proportional hazards models assessed risk factors for further surgery. RESULTS 12 230 patients were identified: 45% male; median age 36 (IQR 26-49) years. Median follow-up was 5.9 (IQR 3.6-8.6) years: totalling 74 960 person-years. Median time to further surgery was 2.9 (IQR 1.2-5.3) years. By 5 years 9% and by 10 years 16.9% of those with sufficient follow-up had at least one further surgery involving the anastomotic site. Older, less deprived patients and those whose index surgery took place on an elective admission had a reduced risk of further surgery. The annual number of right hemicolectomies increased over the study from 1063 to 1317, driven by the increasing prevalence of CD. Overall, 78% of patients did not have a colonoscopy, as recommended, within 6-12 months following index resection. CONCLUSIONS Further surgery involving the anastomotic site remains common following index right hemicolectomy for CD. Post-surgical colonoscopy was only undertaken in 22% of patients within suggested timeframes. Increased colonoscopy may lead to a reduced need for surgery if early optimisation of medical therapy is undertaken for recurrence