Treatment outcomes with oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c diabetes): A population-based cohort study.

Aims: To assess outcomes of oral anti-hyperglycaemic therapies in people with diabetes secondary to a pancreatic condition (type 3c), where specific treatment guidance is limited.

Materials And Methods: Using hospital-linked UK primary care records (Clinical Practice Research Datalink; 2004-2020), we identified 7084 people with a pancreatic condition (acute pancreatitis, chronic pancreatitis, pancreatic cancer and haemochromatosis) preceding diabetes diagnosis (type 3c cohort), initiating oral glucose-lowering therapy (metformin, sulphonylureas, SGLT2-inhibitors, DPP4-inhibitors or thiazolidinediones), and without concurrent insulin treatment. We stratified by pancreatic exocrine insufficiency [PEI] (n = 5917 without PEI, 1167 with PEI) and matched to 97 227 type 2 diabetes (T2D) controls.

Safety and effectiveness of SGLT2 inhibitors in a UK population with type 2 diabetes and aged over 70 years: an instrumental variable approach.

Aims/hypothesis: Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in people with type 2 diabetes aged over 70 years using causal analysis.

Methods: Hospital-linked UK primary care data (Clinical Practice Research Datalink, 2013-2020) were used to compare adverse events and effectiveness in individuals initiating SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i).

Gonadal hormone deprivation regulates response to tibolone in neurodegenerative pathways.

Gonadal hormone deprivation (GHD) and decline such as menopause and bilateral oophorectomy are associated with an increased risk of neurodegeneration. Yet, hormone therapies (HTs) show varying efficacy, influenced by factors such as sex, drug type, and timing of treatment relative to hormone decline. We hypothesize that the molecular environment of the brain undergoes a transition following GHD, impacting the effectiveness of HTs.

Phenotype-based targeted treatment of SGLT2 inhibitors and GLP-1 receptor agonists in type 2 diabetes.

Aims/hypothesis: A precision medicine approach in type 2 diabetes could enhance targeting specific glucose-lowering therapies to individual patients most likely to benefit. We aimed to use the recently developed Bayesian causal forest (BCF) method to develop and validate an individualised treatment selection algorithm for two major type 2 diabetes drug classes, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA).

Methods: We designed a predictive algorithm using BCF to estimate individual-level conditional average treatment effects for 12-month glycaemic outcome (HbA) between SGLT2i and GLP1-RA, based on routine clinical features of 46,394 people with type 2 diabetes in primary care in England (Clinical Practice Research Datalink; 27,319 for model development, 19,075 for hold-out validation), with additional external validation in 2252 people with type 2 diabetes from Scotland (SCI-Diabetes [Tayside & Fife]).

Risk factor associations for severe COVID-19, influenza and pneumonia in people with diabetes to inform future pandemic preparations: UK population-based cohort study.

Objective: This study aimed to compare clinical and sociodemographic risk factors for severe COVID-19, influenza and pneumonia, in people with diabetes.

Design: Population-based cohort study.

Setting: UK primary care records (Clinical Practice Research Datalink) linked to mortality and hospital records.

Recent UK type 2 diabetes treatment guidance represents a near whole population indication for SGLT2-inhibitor therapy.

Recent type 2 diabetes guidance from the UK's National Institute for Health and Care Excellence (NICE) proposes offering SGLT2-inhibitor therapy to people with established atherosclerotic cardiovascular disease (ASCVD) or heart failure, and considering SGLT2-inhibitor therapy for those at high-risk of cardiovascular disease defined as a 10-year cardiovascular risk of > 10% using the QRISK2 algorithm. We used a contemporary population-representative UK cohort of people with type 2 diabetes to assess the implications of this guidance. 93.

Data-Resource Profile: United Kingdom Optimum Patient Care Research Database.

Introduction: Electronic medical records (EMRs) maintained in primary care in the UK and collected and stored in EMR databases offer a world-leading resource for observational clinical research. We aimed to profile one such database: the Optimum Patient Care Research Database (OPCRD).

Methods And Participants: The OPCRD, incepted in 2010, is a growing primary care EMR database collecting data from 992 general practices within the UK.

Precision medicine in type 2 diabetes: A systematic review of treatment effect heterogeneity for GLP1-receptor agonists and SGLT2-inhibitors.

Background: A precision medicine approach in type 2 diabetes requires identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy.

Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes.

Studies are needed to support optimal insulin dose titration in gestational diabetes mellitus: A systematic review.

Background And Aims: We aimed to summarise the existing literature on insulin dose titration in gestation diabetes.

Methods: Databases: Medline, EMBASE, CENTRAL and CINAHL were systematically searched for trials and observational studies comparing insulin titration strategies in gestational diabetes.

Results: No trials comparing insulin dose titration strategies were identified.

Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Novel Heterobifunctional Small Molecule Therapeutic Strategy for Killing Cancer Cells Selectively.

While specific cell signaling pathway inhibitors have yielded great success in oncology, directly triggering cancer cell death is one of the great drug discovery challenges facing biomedical research in the era of precision oncology. Attempts to eradicate cancer cells expressing unique target proteins, such as antibody-drug conjugates (ADCs), T-cell engaging therapies, and radiopharmaceuticals have been successful in the clinic, but they are limited by the number of targets given the inability to target intracellular proteins. More recently, heterobifunctional small molecules such as Proteolysis Targeting Chimera (PROTACs) have paved the way for protein proximity inducing therapeutic modalities.

Effect of integrated exercise therapy and psychosocial interventions on self-efficacy in patients with chronic low back pain: A systematic review.

Objective: Investigate if integrated exercise and psychosocial (EP) interventions effect self-efficacy to manage pain and self-efficacy for physical functioning compared to alternate interventions, usual care, waitlists and attention controls for individuals with chronic low back pain (CLBP).

Methods: MEDLINE, Embase, CINAHL, Web of Science, PsychINFO, PEDro, and Cochrane Library were searched. Included randomized controlled trials utilized an EP intervention for CLBP and measured self-efficacy.

Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain.

The existence of sex differences in disease incidence is attributed, in part, to sex differences in metabolism. Uncovering the precise mechanism driving these differences is an extraordinarily complex process influenced by genetics, endogenous hormones, sex-specific lifetime events, individual differences and external environmental/social factors. In fact, such differences may be subtle, but across a life span, increase susceptibility to a pathology.

Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes: a retrospective cohort study.

Background: Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies.

Methods: In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD).

The impact of population-level HbA screening on reducing diabetes diagnostic delay in middle-aged adults: a UK Biobank analysis.

Aims/hypothesis: Screening programmes can detect cases of undiagnosed diabetes earlier than symptomatic or incidental diagnosis. However, the improvement in time to diagnosis achieved by screening programmes compared with routine clinical care is unclear. We aimed to use the UK Biobank population-based study to provide the first population-based estimate of the reduction in time to diabetes diagnosis that could be achieved by HbA-based screening in middle-aged adults.

Identifying type 1 and 2 diabetes in research datasets where classification biomarkers are unavailable: assessing the accuracy of published approaches.

Objectives: We aimed to compare the performance of approaches for classifying insulin-treated diabetes within research datasets without measured classification biomarkers, evaluated against two independent biological definitions of diabetes type.

Study Design And Setting: We compared accuracy of ten reported approaches for classifying insulin-treated diabetes into type 1 (T1D) and type 2 (T2D) diabetes in two cohorts: UK Biobank (UKBB) n = 26,399 and Diabetes Alliance for Research in England (DARE) n = 1,296. The overall performance for classifying T1D and T2D was assessed using: a T1D genetic risk score and genetic stratification method (UKBB); C-peptide measured at >3 years diabetes duration (DARE).

Sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: Are clinical trial benefits for heart failure reflected in real-world clinical practice? A systematic review and meta-analysis of observational studies.

Aim: To determine the absolute risk reduction (ARR) of heart failure events in people treated with sodium-glucose co-transporter-2 (SGLT2) inhibitors.

Materials And Methods: We searched PubMed, EMBASE, CINAHL and ISI Web of Science for observational studies published to 9 May 2022 that explored the association between SGLT2 inhibitors and any indication for heart failure (including new diagnosis or hospitalization for heart failure) in type 2 diabetes. Identified studies were independently screened by two reviewers and assessed for bias using the Newcastle-Ottawa scale.

Barriers and Facilitators to the Initiation of Injectable Therapies for Type 2 Diabetes Mellitus: A Mixed Methods Study.

Introduction: Initiation of injectable therapies in type 2 diabetes (T2D) is often delayed, however the reasons why are not fully understood.

Methods: A mixed methods study performed in sequential phases. Phase 1: focus groups with people with T2D (injectable naïve [n = 12] and experienced [n = 5]) and healthcare professionals (HCPs; nurses [n = 5] and general practitioners (GPs) [n = 7]) to understand their perceptions of factors affecting initiation of injectables.

Patient-led rapid titration of basal insulin in gestational diabetes is associated with improved glycaemic control and lower birthweight.

Aims: Elevated fasting blood glucose in gestational diabetes (GDM) is a key predictor of high birthweight babies and adverse pregnancy outcomes but is hard to treat. We implemented a simple, patient-led, insulin dose titration algorithm aiming to improve fasting glycaemic control in GDM.

Methods: In women with GDM, initiating basal insulin, we recommended a daily four-unit dose increase after every fasting glucose value ≥5.

Atopic dermatitis and risk of autoimmune conditions: Population-based cohort study.

Background: Atopic dermatitis (AD) is associated with immune dysregulation, but epidemiologic data on the pattern of autoimmune comorbidity in people with AD are limited.

Objective: We sought to determine the risk of autoimmune conditions in people newly diagnosed with AD.

Methods: Retrospective cohort analysis (January 2009 to December 2018), using the UK-based Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care database.