Meta-Analysis of Cardiovascular Efficacy of Empagliflozin Versus Dapagliflozin in Type 2 Diabetes: Unveiling Key Insights

The favorable safety profile of sodium-glucose cotransporter 2 inhibitors, notably empagliflozin and dapagliflozin, makes them a suitable treatment option for type 2 diabetes. However, the comparative cardiovascular (CV) benefits of empagliflozin versus dapagliflozin require further investigation. A comprehensive search of electronic databases was conducted from inception till November 7, 2024. Studies reporting CV outcomes of empagliflozin and dapagliflozin were included in the meta-analysis. The random-effects model was used to pool the risk ratio (RR) along with the corresponding 95% confidence intervals (CIs) for all outcomes. We pooled 8 studies with a total of 428,940 participants. The evaluation of pooled results demonstrated that empagliflozin was associated with a nonsignificant association in reducing all-cause death (RR: 0.91, 95% CI: 0.68-1.20), CV death (RR: 1.12, 95% CI: 0.81-1.55), major adverse cardiovascular events (RR: 1.03, 95% CI: 0.86-1.23), myocardial infarction (RR: 1.01, 95% CI: 0.84-1.22), stroke (RR: 0.90, 95% CI: 0.79-1.04), and heart failure-related events (RR: 1.07, 95% CI: 0.87-1.32). This study does not suggest a clear CV benefit of using empagliflozin over dapagliflozin, or vice versa, as an add-on therapy for type 2 diabetes. If both medications have similar safety profiles, differences in their costs are likely to impact their cost-effectiveness in CV risk reduction.Unknow

Interleukin-1β Stimulates Matrix Metalloproteinase 10 Secretion: A Possible Mechanism in Trophoblast-Dependent Spiral Artery Remodeling

Maternal uterine spiral arteries (SpA) undergo significant structural changes in early pregnancy, resulting in increased blood flow to the developing fetus. Endothelial cells (EC) and vascular smooth muscle cells (VSMC) are lost from the SpA wall and are replaced by trophoblasts. We have previously shown that matrix metalloproteinase 10 (MMP-10) and Heparin binding-EGF like growth factor (HB-EGF) gene expression is increased in a 3D EC/VSMC co-culture system in response to trophoblast secreted factors. This study investigated trophoblast mediated MMP-10 and HB-EGF expression and determined if there was a relationship between the secretion of MMP-10 and the release of soluble HB-EGF (sHB-EGF) from EC. MMP-10 was widely expressed in first trimester decidual tissue including trophoblast, and EC, but not VSMC. MMP-10 expression was significantly lower in decidual tissue from pregnancies at increased risk of developing pre-eclampsia compared to low-risk pregnancies. In vitro, SGHEC-7 cells, a human EC line, but not SGHVMC-9, a human VSMC cell line, secreted MMP-10 in response to trophoblast conditioned medium (TCM). TCM contains several growth factors and cytokines, but only interleukin-1β (IL1β) significantly stimulated MMP-10 secretion by SGHEC-7 cells. Interleukin-1 receptor antagonist (IL-1Ra) significantly inhibited TCM-induced MMP-10 secretion. Interrogation of intracellular pathways established the involvement of MEK and JNK in TCM and IL-1β stimulated MMP-10 secretion. Although IL-1β also significantly increased sHB-EGF, inhibition of MMP-10 activity using a broad spectrum MMP inhibitor had no effect on sHB-EGF. Western blot analysis indicated that MMP-10 secreted by EC in response to IL-1β stimulation was the enzymatically inactive pro form.CC BY 4.0 (Creative Commons Attribution

Higher surgeon volume reduces early failure in first time revision of non-infected total knee arthroplasty: An analysis using data from the United Kingdom National Joint Registry

PURPOSE: Revision total knee replacement (RevKR) is an increasingly common procedure. It is hypothesised that higher surgical volume is linked to lower levels of adverse outcomes. The aim was to estimate the association of surgical volume on patient outcomes following first single-stage RevKR for non-infected indications. METHODS: This population-based cohort study used data from the United Kingdom National Joint Registry, Hospital Episode Statistics and National Patient Reported Outcome Measures. Patients undergoing procedures between 1 January 2009 and 30 June 2019 were included. The primary outcome measure was re-revision within 2 years; chosen to reflect the quality of the surgical provision. Fixed effect multivariable regression models were used to examine the association between surgeon and surgical unit annual caseload and the risk of adverse outcomes. RESULTS: A total of 8695 patients underwent first time single stage revision for aseptic loosening, instability, or malalignment across 389 surgical units and 1204 surgeons. Following adjustment for age, gender, ASA grade, year of surgery and operation funder, higher surgeon volume was associated with a lower risk of re-revision at 2 years. The risk of re-revision decreased amongst surgeons performing ≥9 annual revisions (OR 0.77, 95% CI 0.62-0.95, p-value = 0.02) compared to those performing <9 annual revisions. CONCLUSIONS: Annual surgeon case volume of ≥9 first single-stage RevKR for non-infected indications is independently associated with reductions in early re-revision. This evidence supports the setting of minimum volume targets to improve outcomes for patients. LEVEL OF EVIDENCE: Level III, retrospective cohort study of prospectively collected data.CC BY 4.0 (Creative Commons Attribution

Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal (UNIVERSAL) study: a prospective observational cohort study protocol

BACKGROUND: Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develop effective treatment strategies. The Understanding Infection, Viral Exacerbation and Respiratory Symptoms at Admission-Longitudinal Study is an observational study which addresses this need by investigating the heterogeneity of RVIs in hospitalised adults, aiming to identify clinical and biological predictors of adverse outcomes. This study aims to bridge critical knowledge gaps in the clinical course and the economic impact of RVIs by characterising the phenotypic diversity of these infections and their recovery patterns following hospital admission and thus assisting with the optimal design of future interventional studies. METHODS AND ANALYSIS: This prospective longitudinal observational study (V.6, 20 September 2023) will be conducted across multiple UK secondary care sites from August 2022 onwards, with an aim to enrol 1000 participants testing positive for RVI. Adults admitted with respiratory symptoms who test positive for RVIs via the BioFire® FilmArray® System or other validated diagnostic PCR tests will be enrolled. The data collected include patient demographics, clinical history, comorbidities and symptoms experienced prior to, during and after hospitalisation with follow-up after discharge at weeks 1, 2, 4, 8, 12 and 26. In addition, biological samples are collected at multiple time points during the hospital stay. The primary endpoints are to study the impact of different RVIs and identify predictors of disease progression and length of stay. Secondary endpoints include time to recovery and healthcare cost. Exploratory endpoints focus on biomarker profiles associated with virus type and clinical outcomes. ETHICS AND DISSEMINATION: The study protocol received ethical approval from the relevant committees (English Ethics Reference Number: 22/WM/0119; Scottish Ethics Reference Number: 22-SS-0101, 20/09/2023). For patients who lack the capacity to consent, the study complies with the Mental Capacity Act 2005, using a consultee process where a family member, carer or an independent clinician may provide assent on behalf of the patient. Data from all the study centres will be analysed together and disseminated through peer-reviewed journals, conference presentations and workshops. The study group will ensure that participants and their families are informed of the study findings promptly and in an accessible format. TRIAL REGISTRATION NUMBER: ISRCTN49183956.CC BY 4.0 (Creative Commons Attribution

A face-to-face survey on the practice of ophthalmic clinicians in the management of dry eye disease in patients undergoing cataract surgery

INTRODUCTION: Dry eye disease (DED) can impact the accuracy of biometry measurements prior to cataract surgery (CS), influence visual performance post-CS, and can be exacerbated by CS. We performed a survey to evaluate the DED practice of clinicians directly caring for CS patients. DESIGN: Prospective face-to-face survey. METHOD: Face-to-face survey consisting of 12 questions relating to CS clinicians' estimations of DED pre- and post-CS, dry eye tests performed, and the management of DED. RESULT: There were one hundred and twenty-seven responders (39% consultants, 37% trainees/fellows, 8% associate specialists, 6% specialty doctors, 8% optometrists, 2% nurse specialists), with a 100% response rate. Sixty-seven percent routinely assessed for DED pre-CS, with 81% anticipating mild to moderative negative effects of CS on DED. Approximately 75% estimated that over 10% of pre-operative patients had asymptomatic DED, with another 10% or more suffering symptomatic DED. Almost 80% estimated that 10% or more of patients suffered DED post-CS. More DED tests were performed pre- compared to post-operatively (p = 0.02). More consultants performed dry eye tests post-operatively compared to non-consultants (p = 0.02). Most common treatment options included lubricating drops (95%), lid hygiene (75%) and night ointment/gels (54%). Seventy-six percent of surgeons performing CS stated they coated the ocular surface with an ophthalmic visco-surgical device and 34% limited intra-operative light exposure peri-operatively to limit DED. DISCUSSION: Despite the anticipated negative effects of CS on DED, 1 in 3 clinicians in our survey were not assessing routinely for DED prior to CS, and fewer dry eye tests were performed post-operatively compared to pre-surgery.This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data

BACKGROUND: Multimorbidity, the presence of two or more conditions in one person, is common but studies are often limited to observational data and single datasets. We address this gap by integrating large-scale primary-care and genetic data from multiple studies to interrogate multimorbidity patterns and producing digital resources to support future research. METHODS: We defined chronic, common, and heritable conditions in individuals aged ≥65 years, using two large primary-care databases [CPRD (UK) N = 2,425,014 and SIDIAP (Spain) N = 1,053,640], and estimated heritability using the same definitions in UK Biobank (N = 451,197). We used logistic regression to estimate the co-occurrence of pairs of conditions in the primary care data. Linkage disequilibrium score regression was used to estimate genetic similarity between pairs of conditions. Meta-analyses were conducted across databases, and up to three sources of genetic data, for each pair of conditions. We classified pairs of conditions as across or within-domain based on the international classification of disease. FINDINGS: We identified 72 chronic conditions, with 43.6% of 2546 pairs showing higher co-occurrence than chance in primary care and evidence of shared genetics. Many across-domain pairs exhibited substantial shared genetics (e.g., iron deficiency anaemia and peripheral arterial disease: genetic correlation R(g) = 0.45 [95% Confidence Intervals 0.27:0.64]). 33 pairs displayed negative genetic correlations, such as skin cancer and rheumatoid arthritis (R(g) = -0.14 [-0.21:-0.06]), due to potential adverse drug effects. Discordance between genetic and primary care data was also observed, e.g., abdominal aortic aneurysm and bladder cancer co-occurred in primary care but were not genetically correlated (Odds-Ratio = 2.23 [2.09:2.37], R(g) = 0.04 [-0.20:0.28]) and schizophrenia and fibromyalgia were less likely to co-occur together in primary care but were positively genetically correlated (OR = 0.84 [0.75:0.94], R(g) = 0.20 [0.11:0.29]). INTERPRETATION: Most pairs of chronic conditions show evidence of shared genetics, and co-occurrence in primary care, suggesting shared mechanisms. The identified patterns of shared genetics, negative correlations and discordance between genetic and observational data provide a foundation for future multimorbidity research. FUNDING: UK Medical Research Council [MR/W014548/1].This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo. Click on the 'Additional link' above to access the full-text

Widening Patient Engagement for Rare Disease Drug Trials: The Perspectives of Patients With Idiopathic Pulmonary Fibrosis on Participating in Clinical Drug Trials and Drug Trial Design

BACKGROUND: Research about patient engagement for people with rare diseases has identified how the experiences of some members of the public are overlooked in relation to clinical trial design and trial participation. As part of a knowledge transfer partnership (KTP), the authors were granted access to patient insight reports about the needs of people with idiopathic pulmonary fibrosis (IPF), to inform clinical trial design and marketing strategy. These were contrasted with data from qualitative interviews, informed by and collected from people with IPF and the clinical staff who recruit them to trials. OBJECTIVE: To identify patient and professional perspectives for IPF drug trials to create opportunities for innovation in patient engagement. DESIGN: Ethnography. Qualitative researcher embedded in a pharmaceutical organisation. SETTING AND PARTICIPANTS: International patient insight reports to inform a clinical trial protocol (n = 1) and marketing strategy (n = 6), including the experiences of over 100 patients with IPF. In the United Kingdom, interviews with patients with IPF (n = 32) and the staff who support them clinically and recruit them to trials of new medicines (n = 19) at one specialist interstitial lung disease (ILD) centre. RESULTS: Methodological practices inherent in inpatient insight reports ensured the perspectives of some people with IPF were overlooked. Interviews with a more marginalised population of people with IPF, and the staff who support them, identified that some found trial information confusing, trial practices frustrating and the opportunities to engage in trial design absent. DISCUSSION: Current pharmaceutical practices of working with contract research organisations and patient organisations exclude the perspectives of patients with IPF who do not engage with either. Trial recruitment information needs to be tailored to the needs of individuals, and trial processes need to enable a wider group of patients to participate. CONCLUSIONS: People with IPF want the opportunity to participate in drug trials and trial science. However, methodological rigour and deliberative practices are required to enable a wider group of patients to have a stake in the design and conduct of drug trials for rare diseases. The challenge now is for regulators to mandate such inclusive practices and for pharmaceutical organisations to adopt them. PATIENT OR PUBLIC CONTRIBUTION: A Patient Advisory Group (PAG) comprising six people with IPF gave input on the research protocol and then on the scope and content of the ongoing research. Two patients from international patient organisations served as a Steering Group (SG). Members of these groups provided their interpretations of the study findings and gave insight on their experiences in clinical design and participation.CC BY 4.0 (Creative Commons Attribution

A Narrative Review of the Evolving Role of Robotic Surgery in Pediatrics: Innovations and Future Prospects

Robot surgery has significantly improved surgical interventions for pediatric patients by enhancing surgical precision, minimizing complications, and improving overall patient outcomes. Over the past few years, substantial advancements in technology and surgical techniques have facilitated the widespread adoption of robotic systems in pediatric surgical procedures across multiple specialties. These encompass specialties such as pediatric urology, general surgery, thoracic surgery, and oncology, contributing to its adoption and widespread implementation in clinical practice. The integration of robotic platforms has enabled surgeons to perform complex procedures with greater dexterity, improved visualization, and enhanced control. This comprehensive review aims to provide an in-depth analysis of the evolution of robotic surgery, its current applications in pediatric surgery, its advantages over conventional surgical techniques, and the potential limitations and challenges associated with its usage and generalization in clinical practice.CC BY 4.0 (Creative Commons Attribution

Developing an adaptive platform trial for evaluation of medical treatments for Crohn's disease

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The significance of isolated de novo red patches in the bladder in patients referred with suspected urinary tract cancer: Results from the IDENTIFY study

OBJECTIVES: To assess the contemporary malignancy rate in isolated de novo red patches in the bladder and associated risk factors for better selection of red patch biopsy. PATIENTS: Patients from the IDENTIFY dataset; Patients referred to secondary care with suspected urinary tract cancer and found to have isolated de novo red patches on cystoscopy. METHODS: We reported the unadjusted cancer prevalence in isolated de novo red patches that were biopsied; multivariable logistic regression was used to explore cancer-associated risk factors including age, sex, smoking, type of haematuria, LUTS, UTIs and a suspicious-looking red patch (as reported by the cystoscopist). Sub-analysis of these by clinical role and experience was performed. RESULTS: A total of 1110 patients with isolated de novo red patches were included. 41.5% (n = 461) were biopsied, with a malignancy rate of 12.8% (59/461), which was significantly higher in suspicious versus non-suspicious red patches (19.1% vs. 2.81%, p < 0.01). There was a significant association between bladder cancer and age (OR 1.04, 95% CI 1.01-1.07, p = 0.01), smoking history (OR 2.62, 95% CI 1.09-6.27, p = 0.03) and suspicious-looking patch (OR 6.50, 95% CI 2.47-17.1, p < 0.01). The majority of malignancies were in over 60-year-olds. Malignancy rates in suspicious versus non-suspicious red patches did not differ significantly between clinical roles or experiences.Limitations included subjectivity in classifying a suspicious patch and selection bias as not all patches were biopsied. CONCLUSIONS: Many patients still undergo unnecessary biopsies under general anaesthetic for isolated de novo red patches. Clinicians should consider the patient's age, smoking status and how suspicious-looking the patch is, before deciding on surveillance versus biopsy to improve cancer diagnostic yield.This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Journal content freely available via Open Access. Some content may be unavailable due to publisher embargo