Cardiovascular disease (CVD) is the leading cause of mortality in people with type 2 diabetes mellitus (T2DM), yet a significant proportion of the disease burden cannot be accounted for by conventional cardiovascular risk factors. Hypertension occurs in majority of people with T2DM, which is substantially more frequent than would be anticipated based on general population samples. The impact of hypertension is considerably higher in people with diabetes than it is in the general population, suggesting either an increased sensitivity to its effect or a confounding underlying aetiopathogenic mechanism of hypertension associated with CVD within diabetes. In this contribution, we aim to review the changes observed in the vascular tree in people with T2DM compared to the general population, the effects of established anti-diabetes drugs on microvascular outcomes, and explore the hypotheses to account for common causalities of the increased prevalence of CVD and hypertension in people with T2DM.

SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

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Age is a primary risk factor for cardiovascular disease, and this is an increasingly important public health concern because of an increase in the absolute number and proportion of the population at an older age in many countries. A key component of cardiovascular ageing is reduced function of the vascular endothelium, and this probably contributes to the impaired microvessel function observed with ageing in multiple vascular beds. In turn, impaired microvessel function is thought to contribute to the pathophysiology of cardiovascular and metabolic diseases. Here we review evidence that the first signs of altered endothelial and microvessel function can appear in childhood and at all stages of the human lifespan; low-birth-weight babies have reduced endothelial function in skin microvessels at 3 months, and by age 10 years their brachial artery endothelial function is reduced in comparison with normal-birth-weight babies. In overweight/obese adolescent children with clustering of traditional cardiovascular disease risk factors, endothelial function is reduced compared with normal-weight children, and this appears to persist into early adulthood. Adult ageing is associated with impaired microvessel endothelial function and an increase in capillary blood pressure. Biological and lifestyle factors that influence microvessel function include body fat and visceral adiposity, sex hormone status, diet and physical activity. The mechanisms underlying age-associated changes in microvessel function are uncertain but may involve alterations in nitric oxide, prostanoid, endotheliumderived hyperpolarizing factor(s) and endothelin-1 pathways.

Introduction Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

The principal findings of this survey suggest that impairments in communication are at the heart of clinical inertia. This manuscript lays out four key principles that we believe are achievable in all environments and can improve the lives of people with diabetes.

Summary Background Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding British Heart Foundation.

background Despite simpler regimens than vitamin K antagonists (VKas) for stroke prevention in atrial fibrillation (aF), adherence (taking drugs as prescribed) and persistence (continuation of drugs) to direct oral anticoagulants are suboptimal, yet understudied in electronic health records (ehrs). Objective We investigated (1) time trends at individual and system levels, and (2) the risk factors for and associations between adherence and persistence. Methods in UK primary care ehr (The health information network 2011-2016), we investigated adherence and persistence at 1 year for oral anticoagulants (Oacs) in adults with incident aF. Baseline characteristics were analysed by Oac and adherence/persistence status. risk factors for nonadherence and non-persistence were assessed using cox and logistic regression. Patterns of adherence and persistence were analysed. results among 36 652 individuals with incident aF, cardiovascular comorbidities (median cha 2 Ds 2 Vasc[congestive heart failure, hypertension, age≥75 years, Diabetes mellitus, stroke, Vascular disease, age 65-74 years, sex category] 3) and polypharmacy (median number of drugs 6) were common. adherence was 55.2% (95% ci 54.6 to 55.7), 51.2% (95% ci 50.6 to 51.8), 66.5% (95% ci 63.7 to 69.2), 63.1% (95% ci 61.8 to 64.4) and 64.7% (95% ci 63.2 to 66.1) for all Oacs, VKa, dabigatran, rivaroxaban and apixaban.One-year persistence was 65.9% (95% ci 65.4 to 66.5), 63.4% (95% ci 62.8 to 64.0), 61.4% (95% ci 58.3 to 64.2), 72.3% (95% ci 70.9 to 73.7) and 78.7% (95% ci 77.1 to 80.1) for all Oacs, VKa, dabigatran, rivaroxaban and apixaban. risk of non-adherence and non-persistence increased over time at individual and system levels. increasing comorbidity was associated with reduced risk of non-adherence and non-persistence across all Oacs. Overall rates of 'primary non-adherence' (stopping after first prescription), 'non-adherent nonpersistence' and 'persistent adherence' were 3.5%, 26.5% and 40.2%, differing across Oacs. Conclusions adherence and persistence to Oacs are low at 1 year with heterogeneity across drugs and over time at individual and system levels. Better understanding of contributory factors will inform interventions to improve adherence and persistence across Oacs in individuals and populations.on July 10, 2020 by guest. Protected by copyright.