Phyo Kyaw Myint

BACKGROUND: The COVID-19 pandemic has placed unprecedented strain on health-care systems. Frailty is being used in clinical decision making for patients with COVID-19, yet the prevalence and effect of frailty in people with COVID-19 is not known. In the COVID-19 in Older PEople (COPE) study we aimed to establish the prevalence of frailty in patients with COVID-19 who were admitted to hospital and investigate its association with mortality and duration of hospital stay. METHODS: This was an observational cohort study conducted at ten hospitals in the UK and one in Italy. All adults (≥18 years) admitted to participating hospitals with COVID-19 were included. Patients with incomplete hospital records were excluded. The study analysed routinely generated hospital data for patients with COVID-19. Frailty was assessed by specialist COVID-19 teams using the clinical frailty scale (CFS) and patients were grouped according to their score (1-2=fit; 3-4=vulnerable, but not frail; 5-6=initial signs of frailty but with some degree of independence; and 7-9=severe or very severe frailty). The primary outcome was in-hospital mortality (time from hospital admission to mortality and day-7 mortality). FINDINGS: Between Feb 27, and April 28, 2020, we enrolled 1564 patients with COVID-19. The median age was 74 years (IQR 61-83); 903 (57·7%) were men and 661 (42·3%) were women; 425 (27·2%) had died at data cutoff (April 28, 2020). 772 (49·4%) were classed as frail (CFS 5-8) and 27 (1·7%) were classed as terminally ill (CFS 9). Compared with CFS 1-2, the adjusted hazard ratios for time from hospital admission to death were 1·55 (95% CI 1·00-2·41) for CFS 3-4, 1·83 (1·15-2·91) for CFS 5-6, and 2·39 (1·50-3·81) for CFS 7-9, and adjusted odds ratios for day-7 mortality were 1·22 (95% CI 0·63-2·38) for CFS 3-4, 1·62 (0·81-3·26) for CFS 5-6, and 3·12 (1·56-6·24) for CFS 7-9. INTERPRETATION: In a large population of patients admitted to hospital with COVID-19, disease outcomes were better predicted by frailty than either age or comorbidity. Our results support the use of CFS to inform decision making about medical care in adult patients admitted to hospital with COVID-19. FUNDING: None.

OBJECTIVE: Glycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Medline and Embase were searched (2004-2015) for studies describing associations between HbA1c variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA1c variability, method of analysis, and diabetes type. RESULTS: Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c variability with renal disease (risk ratio 1.56 [95% CI 1.08-2.25], two studies), cardiovascular events (1.98 [1.39-2.82]), and retinopathy (2.11 [1.54-2.89]). Thirteen studies evaluated HbA1c variability among patients with type 2 diabetes. Higher HbA1c variability was associated with higher risk of renal disease (1.34 [1.15-1.57], two studies), macrovascular events (1.21 [1.06-1.38]), ulceration/gangrene (1.50 [1.06-2.12]), cardiovascular disease (1.27 [1.15-1.40]), and mortality (1.34 [1.18-1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA1c variability. CONCLUSIONS: HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment.

OBJECTIVES: To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia. DESIGN: Case-control study. SETTING: General practices in the UK contributing to the Clinical Practice Research Datalink. PARTICIPANTS: 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia. INTERVENTIONS: Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia. MAIN OUTCOME MEASURES: Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates. RESULTS: 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis. CONCLUSIONS: A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure. TRIAL REGISTRATION: Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.

A high rate of polypharmacy is, in part, a consequence of the increasing proportion of multimorbidity in the ageing population worldwide. Our understanding of the potential harm of taking multiple medications in an older, multi-morbid population, who are likely to be on a polypharmacy regime, is limited. This is a narrative literature review that aims to appraise and summarise recent studies published about polypharmacy. We searched MEDLINE using the search terms polypharmacy (and its variations, e.g. multiple prescriptions, inappropriate drug use, etc.) in titles. Systematic reviews and original studies in English published between 2003 and 2018 were included. In this review, we provide current definitions of polypharmacy. We identify the determinants and prevalence of polypharmacy reported in different studies. Finally, we summarise some of the findings regarding the association between polypharmacy and health outcomes in older adults, with a focus on frailty, hospitalisation and mortality. Polypharmacy was most often defined in terms of the number of medications that are being taken by an individual at any given time. Our review showed that the prevalence of polypharmacy varied between 10% to as high as around 90% in different populations. Chronic conditions, demographics, socioeconomics and self-assessed health factors were independent predictors of polypharmacy. Polypharmacy was reported to be associated with various adverse outcomes after adjusting for health conditions. Optimising care for polypharmacy with valid, reliable measures, relevant to all patients, will improve the health outcomes of older adult population.

OBJECTIVE: hip fracture is a common and serious condition associated with high mortality. This study aimed to identify pre-operative characteristics which are associated with an increased risk of mortality after hip fracture surgery. DESIGN: systematic search of published and unpublished literature databases, including EMBASE, MEDLINE, AMED, CINAHL, PubMed and the Cochrane Library, was undertaken to identify all clinical studies on pre-operative predictors of mortality after surgery in hip fracture with at least 3-month follow-up. Data pertaining to the study objectives was extracted by two reviewers independently. Where study homogeneity was evidence, a meta-analysis of pooled relative risk and 95% confidence intervals was performed for mortality against pre-admission characteristics. RESULTS: fifty-three studies including 544,733 participants were included. Thirteen characteristics were identified as possible pre-operative indicators for mortality. Following meta-analysis, the four key characteristics associated with the risk of mortality up to 12 months were abnormal ECG (RR: 2.00; 95% CI: 1.45, 2.76), cognitive impairment (RR: 1.91; 95% CI: 1.35, 2.70), age >85 years (RR: 0.42; 95% CI: 0.20, 0.90) and pre-fracture mobility (RR: 0.13; 95% CI: 0.05, 0.34). Other statistically significant pre-fracture predictors of increased mortality were male gender, being resident in a care institution, intra-capsular fracture type, high ASA grade and high Charlson comorbidity score on admission. CONCLUSIONS: this review has identified the characteristics of patients with a high risk of mortality after a hip fracture surgery beyond the peri-operative period who may benefit from comprehensive assessment and appropriate management. PROSPERO REGISTRATION NUMBER: CRD42012002107.