Reecha sofat

INTRODUCTION: Free-of-charge (FoC) medicine schemes are increasingly available and allow access to investigational treatments outside clinical trials or in advance of licensing or NHS commissioning. METHODS: We retrospectively reviewed FoC medicine schemes evaluated between 2013 and 2019 by a single NHS trust and a regional drug and therapeutics committee (DTC). The details of each locally reviewed FoC scheme, and any nationally available Medicines and Healthcare products Regulatory Agency Early Access to Medicines Scheme (MHRA EAMS) in the same period, were recorded and categorised...

Background: We aimed to evaluate atrial fibrillation occurrence, reasons for healthcare visits, mortality, causes of death and examined patterns by relative deprivation in the UK. Methods: To study the atrial fibrillation (AF) incidence, mortality and case-fatality, we implemented a prospective cohort study with the linked electronic health records of 5.6 million population in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. A matched case-control study was used to investigate causes of hospitalisation and death comparing individuals with and without incident AF...

With over 117 million COVID-19-positive cases declared and the death count approaching 3 million, we would expect that the highly digitalized health systems of high-income countries would have collected, processed, and analyzed large quantities of clinical data from patients with COVID-19. Those data should have served to answer important clinical questions such as: what are the risk factors for becoming infected? What are good clinical variables to predict prognosis? What kinds of patients are more likely to survive mechanical ventilation? Are there clinical subphenotypes of the disease? All these, and many more, are crucial questions to improve our clinical strategies against the epidemic and save as many lives as possible...

Reducing the burden of late-life morbidity requires an understanding of the mechanisms of ageing-related diseases (ARDs), defined as diseases that accumulate with increasing age. This has been hampered by the lack of formal criteria to identify ARDs. Here, we present a framework to identify ARDs using two complementary methods consisting of unsupervised machine learning and actuarial techniques, which we applied to electronic health records (EHRs) from 3,009,048 individuals in England using primary care data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care dataset between 1 April 2010 and 31 March 2015 (mean age 49...

No abstract text is available yet for this article.

BACKGROUND: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. METHODS: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies. RESULTS: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins...

OBJECTIVE: To monitor hospital activity for presentation, diagnosis and treatment of cardiovascular diseases during the COVID-19) pandemic to inform on indirect effects. METHODS: Retrospective serial cross-sectional study in nine UK hospitals using hospital activity data from 28 October 2019 (pre-COVID-19) to 10 May 2020 (pre-easing of lockdown) and for the same weeks during 2018-2019. We analysed aggregate data for selected cardiovascular diseases before and during the epidemic...

Host immunity is required to clear SARS-CoV-2, and inability to clear the virus because of host or pathogen factors renders those infected at risk of poor outcomes. Estimates of those who are able to clear the virus with asymptomatic or paucisymptomatic COVID-19 remain unclear, and dependent on widespread testing. However, evidence is emerging that in severe cases, pathological mechanisms of hyperinflammation and coagulopathy ensue, the former supported by results from the RECOVERY trial demonstrating a reduction in mortality with dexamethasone in advanced COVID-19...

OBJECTIVES: To report on a retrospective study of individual funding request (IFR) submissions from a large tertiary hospital and describe gaps in current mechanisms for funding of high-cost medicines in England. METHODS: Data on the number and outcome of IFR submissions submitted to commissioners between 2014/15 and 2018/19 was extracted from the electronic patient health record and a local high-cost drug database. RESULTS: In total 230 IFRs were submitted; 112 to NHS England and 118 to a CCG...

There is an increasing awareness that polypharmacy - the use of multiple medicines by one individual - may bring harm as well as benefit. This has been termed 'problematic polypharmacy' and is associated with increased risk of admission to hospital, decreased quality of life and psychological harm. This article addresses the factors that may be contributing to the global rise of polypharmacy (the whys), the problems it can cause (the so whats), and some opportunities and strategies for improving and avoiding problematic polypharmacy in the future (the what nexts)...

There is increasing national and international interest in overprescribing and polypharmacy, and the burden that the inappropriate use of multiple medicines can place on individual patients and on society as a whole. This paper explores the challenges faced by prescribers and pharmacists wishing to reduce polypharmacy, including the uncertainties about the risks and benefits of continuing or stopping individual drugs. We discuss the factors influencing us to prescribe-which may lead to overprescribing-including the increasing number of guidelines, perceived patient pressure and advertising...

In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto-inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings.

Lack of efficacy in the intended disease indication is the major cause of clinical phase drug development failure. Explanations could include the poor external validity of pre-clinical (cell, tissue, and animal) models of human disease and the high false discovery rate (FDR) in preclinical science. FDR is related to the proportion of true relationships available for discovery (γ), and the type 1 (false-positive) and type 2 (false negative) error rates of the experiments designed to uncover them. We estimated the FDR in preclinical science, its effect on drug development success rates, and improvements expected from use of human genomics rather than preclinical studies as the primary source of evidence for drug target identification...

BACKGROUND: Clinical guidelines and public health authorities lack recommendations on scalable approaches to defining and monitoring the occurrence and severity of bleeding in populations prescribed antithrombotic therapy. METHODS: We examined linked primary care, hospital admission and death registry electronic health records (CALIBER 1998-2010, England) of patients with newly diagnosed atrial fibrillation, acute myocardial infarction, unstable angina or stable angina with the aim to develop algorithms for bleeding events...

OBJECTIVES: To assess the transfer of patients treated with originator biological therapies to biosimilar products in a large UK tertiary referral hospital reflecting practice within the National Health Service (NHS) using prospectively collected data by a hospital based registry administered by the Biologics Steering Group (BSG). METHODS: We analysed data collected prospectively in a hospital-based registry in a large NHS tertiary referral hospital in the United Kingdom...

Background: To effectively prevent, detect, and treat health conditions that affect people during their lifecourse, health-care professionals and researchers need to know which sections of the population are susceptible to which health conditions and at which ages. Hence, we aimed to map the course of human health by identifying the 50 most common health conditions in each decade of life and estimating the median age at first diagnosis. Methods: We developed phenotyping algorithms and codelists for physical and mental health conditions that involve intensive use of health-care resources...

No abstract text is available yet for this article.

INTRODUCTION: Lung cancer screening (LCS) by low-dose computed tomography (LDCT) offers an opportunity to impact both lung cancer and coronary heart disease mortality through detection of coronary artery calcification (CAC). Here, we explore the value of CAC and cardiovascular disease (CVD) risk assessment in LCS participants in the Lung Screen Uptake Trial (LSUT). METHODS: In this cross-sectional study, current and ex-smokers aged 60-75 were invited to a 'lung health check'...

Objectives. Determine the optimal, licensed, first-line anticoagulant for prevention of ischemic stroke in patients with non-valvular atrial fibrillation (AF) in England and Wales from the UK National Health Service (NHS) perspective and estimate value to decision making of further research. Methods. We developed a cost-effectiveness model to compare warfarin (international normalized ratio target range 2-3) with directly acting (or non-vitamin K antagonist) oral anticoagulants (DOACs) apixaban 5 mg, dabigatran 150 mg, edoxaban 60 mg, and rivaroxaban 20 mg, over 30 years post treatment initiation...

BACKGROUND: Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example. METHODS: We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality...