Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

End-to-end deep-learning model for the detection of coronary artery stenosis on coronary CT images.

Purpose: We examined whether end-to-end deep-learning models could detect moderate (≥50%) or severe (≥70%) stenosis in the left anterior descending artery (LAD), right coronary artery (RCA) or left circumflex artery (LCX) in iodine contrast-enhanced ECG-gated coronary CT angiography (CCTA) scans.

Methods: From a database of 6293 CCTA scans, we used pre-existing curved multiplanar reformations (CMR) images of the LAD, RCA and LCX arteries to create end-to-end deep-learning models for the detection of moderate or severe stenoses. We preprocessed the images by exploiting domain knowledge and employed a transfer learning approach using EfficientNet, ResNet, DenseNet and Inception-ResNet, with a class-weighted strategy optimised through cross-validation.

What is the risk of transfusing group O RhD-positive red blood cells to female service personnel of childbearing potential?

The traditional approach to resuscitating injured women of childbearing potential (WCBP) with an unknown RhD type is to transfuse RhD-negative blood products. This is to prevent alloimmunisation to the RhD antigen and ultimately prevent haemolytic disease of the fetus and newborn (HDFN) in future pregnancies should she survive. RhD-negative blood products are scarce in both military and civilian blood stocks.

Whole body vibrations and lower back pain: a systematic review of the current literature.

Introduction: Whole body vibration (WBV) is thought to be associated with low back pain (LBP). To mitigate against this the International Organisation for Standardisation (ISO) have created the ISO 2631 standard, recommending safe dose limits. The aim of this research is to conduct a systematic review of available literature addressing the question, is WBV associated with LBP?

Methods: A literature search was performed from January 1970 until April 2022, including studies focusing on LBP and sciatica in association with WBV, looking specifically for ones reporting on military populations.

Safe Implementation of Treatments in Stroke: a study on intravenous thrombolysis in patients over 80 years of age with acute ischaemic stroke.

Objectives: To investigate the safety and efficacy outcomes of intravenous thrombolysis (IVT) in patients aged >80 years with acute ischaemic stroke (AIS) after IVT was approved in this patient population in several European and non-European countries during 2018-2019.

Design: This is an observational registry study using prospectively collected data from the Safe Implementation of Treatment in Stroke (SITS) registry. Comparisons will be performed between patients treated post-approval (July 2018 to December 2021) period with those treated pre-approval (June 2015 to June 2018) period using propensity score matching (PSM).

Engaging with young professionals in transfusion medicine: Insights from a needs assessment survey targeting an international cohort.

Background And Objectives: Professionals who work or study in transfusion medicine under 40 years of age are considered young professionals (YPs) by the International Society of Blood Transfusion (ISBT). While the ISBT provides opportunities for YPs, their needs have to be assessed to customize initiatives in a way that could potentially improve their engagement. This survey aimed to assess the needs of YPs in transfusion medicine and understand their perspectives on future ISBT initiatives.

Integration of a specialist pharmacist-led multidisciplinary team in primary care: preventing strokes in people with atrial fibrillation across North East London.

Public Health England outlines a national ambition of anticoagulating 90% of eligible patients with atrial fibrillation (AF) by 2029. In 2019/2020, two out of three boroughs reviewed in this study were in the bottom 10% of boroughs compared with others within England. Stroke National Audit data for these three boroughs from 2019 to 2020 identified that in patients with known AF admitted to hospital with strokes, 37% were not anticoagulated.

Evolution and effectiveness of bilateral and multilateral development assistance for health: a mixed-methods review of trends and strategic shifts (1990-2022).

Background: Development assistance for health (DAH) plays a vital role in supporting health programmes in low- and middle-income countries. While DAH has historically focused on infectious diseases and maternal and child health, there is a lack of comprehensive analysis of DAH trends, strategic shifts and their impact on health systems and outcomes. This study aims to provide a comprehensive review of DAH from 1990 to 2022, examining its evolution and funding allocation shifts.

Stewarding COVID-19 health systems response in Pakistan: what more can be done for a primary health care approach to future pandemics?

We apply a primary healthcare (PHC) perspective to gauge Pakistan's health systems response to COVID-19, to identify stewardship lessons for integrating the PHC pandemic response. Analysis of Pakistan's response against the Astana PHC framework shows that the imperative for national survival helped mobilise an agile response across a fragmented health security context. The findings show effective multisector governance in responding to the health and social aspects of the pandemic, as well as the rapid roll-out of several public health functions and emergency care.

Cataract surgery has minimal effect on corneal shape.

Purpose: To quantify the effect of cataract surgery on cornea shape.

Methods: Patients undergoing cataract surgery with standardised 2.75 mm surgical incisions at 110 degrees with a side port at 50 degrees were included.

Prevalence of visually significant cataract and cataract surgical coverage in Indigenous and non-Indigenous Australians: a systematic review and meta-analysis.

Aims: Compare the prevalence of age-related cataract and the cataract surgical coverage rate between Indigenous and non-Indigenous Australians and explore differences in these estimates across location and time.

Methods: The Joanna Briggs Institute guidance for systematic reviews of prevalence studies was followed. A systematic search of Medline, Embase, Web of Science and grey literature from database inception to June 2022 was performed.

A survey of NHS nurses' delivery of treatments to prevent recurrence of venous leg ulcers.

Preventing recurrence of venous leg ulcers can be achieved through strongest tolerated compression and endo-venous ablation surgery, but it is not clear how often this is done in practice. This study explores (1) nurses' awareness of strongest tolerated compression and endo-venous ablation surgery as prophylactic treatments for venous leg ulcer, (2) how often these treatments are offered, and (3) assessment of the barriers and enablers to deploying those treatments using the capabilities, opportunities and motivations model of behaviour change. An online cross-sectional survey was conducted among nurses who treat and manage venous leg ulcers across the United Kingdom.

Early Years Practitioners' and Public Health Consultants' Perspectives on the Use of Interactive Electronic Devices in Young Children: A Qualitative Study.

Background: Interactive electronic devices (IEDs) are ubiquitous in young children's lives. However, research on their impact on learning and development is still limited. The aim of this study was to understand the perspectives of early years practitioners (EYPs) and public health consultants (PHCs) on the use of IEDs in children aged 3-5.

A qualitative exploration of the barriers and facilitators to early lower limb assessment and onward referral for specialist treatment for patients with venous ulceration.

Guidance for venous leg ulceration (VLU) recommends compression therapy and early referral for specialist vascular assessment within two weeks. Few patients receive timely assessment and referral. Reasons for this are unclear.

Conference report from the abstracts of the canine section at The 9th International Conference on Canine and Equine Locomotion, Utrecht 2023.

This conference report summarises the abstracts on canine locomotion research presented in The 9th International Conference on Canine and Equine Locomotion, discusses the most relevant literature in relation to the topics presented in the meeting and highlights the importance of canine locomotion in veterinary medicine.

Predicting Elevated Postvoid Residual Urine Volume Following OnabotulinumtoxinA Treatment for Overactive Bladder: A Pilot Study.

Objectives: To evaluate possible predictors of elevated postvoid residual volume (PVR) following onabotulinumtoxinA administration in patients with idiopathic overactive bladder (OAB), a condition that may include urinary urgency, frequency, and nocturia, without any identifiable cause or underlying neurological or metabolic condition.

Methods: Adults who had been treated with 100-200 U onabotulinumtoxinA for OAB and had previous failure of other OAB treatments were identified by retrospective review of medical chart data from three urology clinics in the United States treating patients with a variety of urological conditions. A total of 211 patients were allocated to cohorts based on posttreatment PVR < 200 mL (n = 173) and ≥ 200 mL (n = 38).

Incidence Trends in Head and Neck Cancer Subsites: A National Population-Based Study (2001-2020).

Objectives: This descriptive epidemiological study aims to investigate trends in head and neck cancer (HNC) within the anatomical divisions of laryngeal, oropharyngeal, and oral cavity cancers over the past two decades.

Design: Retrospective population-based observational study.

Setting: Scotland, a constituent country of the United Kingdom, with a population of 5.

Separating the Effects of Early-Life and Adult Body Size on Chronic Kidney Disease Risk: A Mendelian Randomization Study.

Background: Whether there is a causal relationship between childhood obesity and increased risk of chronic kidney disease (CKD) remains controversial. This study sought to explore how body size in childhood and adulthood independently affects CKD risk in later life using a Mendelian randomization (MR) approach.

Methods: Univariate and multivariate MR was used to estimate total and independent effects of body size exposures.

In-depth Computational Analysis Reveals The Significant Dysregulation of Key Gap Junction Proteins (GJPs) Driving Thoracic Aortic Aneurysm Development.

Objective: Thoracic Aortic Aneurysm (TAA) represents an aortic pathology that is caused by the deranged integrity of the three layers of the aortic wall, and is related to severe morbidity and mortality. Consequently, it is crucial to identify the biomarkers implicated in the pathogenesis and biology of TAA. The aim of the current computational study was to assess the differential gene expression profile of the gap junction proteins (GJPs) in patients with TAA in order to identify novel potential biomarkers for the diagnosis and treatment of this disease.

The role of meal timing in appetitive responses to acute exercise in adolescents with and without obesity: A systematic review and meta-analysis.

Physical activity has been shown to improve various aspects of metabolic health and is frequently applied as an intervention in the management and prevention of overweight/obesity. Chrono-exercise can be studied in relation to time of day and timing in relation to a meal, which encompasses chronology and duration of the temporal interval, but the latter has received limited attention to date. This brief review and meta-analysis investigates whether the timing of a meal subsequent to acute exercise, in children and adolescents with and without overweight/obesity, moderates eating behaviour and appetite.

Genetic diversity and intercontinental dispersal of temperate and subarctic populations of Dibothriocephalus dendriticus (Cestoda; Diphyllobothriidea), a causative agent of dibothriocephalosis.

The diphyllobothriid tapeworm Dibothriocephalus dendriticus, one of the causative agents of the fish-borne zoonosis dibothriocephalosis, is mainly distributed in the Arctic/subarctic and temperate zones of the Northern Hemisphere (Europe, North America, and Asia), but also in the southern cone region of South America (Patagonia). The genetic structure and gene flow among 589 individuals of D. dendriticus, representing 20 populations, were studied using the mitochondrial cox1 gene as the first choice marker and 10 polymorphic nuclear microsatellite loci as a dominant molecular tool.

Burden of vascular risk factors by age, sex, ethnicity and deprivation in young adults with and without newly diagnosed type 2 diabetes.

Aims: Do associations between age at diagnosis of type 2 diabetes and vascular risk factors vary by ethnicity and deprivation?

Methods: Utilising the Clinical Practice Research Datalink, we matched 16-50-year-old individuals with newly diagnosed type 2 diabetes to ∼10 individuals without using sex, age and primary care practice. Differences in BMI, obesity, LDL-cholesterol, HbA1c, and hypertension between individuals with vs without type 2 diabetes across sex, age, ethnicity and deprivation quintiles were explored using generalised linear models.

Results: We included 108,061 individuals (45.

Growing up without violence (GWV): Study protocol for a cluster randomised trial and process evaluation of a school-based intervention preventing adolescent sexual exploitation in Brazil.

Background: Sexual exploitation of children and adolescents (SECA) is a mostly invisible phenomenon, having negative impacts on adolescents' health and well-being.. There is increasing awarenessof preventative strategies to reduce sexual exploitation of children and adolescents, but limited evidence on their effectiveness and mechanisms.

Evaluating student understanding of core pharmacokinetic concepts.

Both educators and graduates have expressed concern about a perceived pharmacology knowledge gap that includes difficulty applying fundamental principles to clinical and research problems. Consequently, we sought to determine the extent to which current students can explain the meaning of, and appropriately apply, a subset of core concepts, and to identify any misconceptions arising from the responses. Of the twenty-four pharmacology core concepts arising from the recent international collaboration, four pharmacokinetic concepts were chosen, namely drug bioavailability, drug clearance, volume of distribution, and steady-state concentration.