Photoreceptor Layer Thinning as Biomarker for Circulatory Premature Mortality: UK Biobank Cohort Study.

Purpose: To explore associations between optical coherence tomography (OCT) parameters and mortality risk.

Methods: This study used data from the UK Biobank participants with eligible OCT data. Feature selection was conducted with the least absolute shrinkage and selection operator.

Seamless monotherapy-combination phase I dose-escalation model-based design.

Phase I dose-escalation studies for a single-agent and combination of anti-cancer agents have explored various model-based designs to guide identification of a maximum tolerated dose and recommended phase II dose. This work describes a parallel approach to dose escalation to expedite identification of maximum tolerated doses both for an anti-cancer agent as monotherapy and in combination with another agent. We develop a three-parameter Bayesian logistic regression model that allows for more efficient use of information between monotherapy and combination parts of the study.

A Trial of Semicircular Canal Plugging vs. Intratympanic Gentamicin for Menière's Disease.

Background: Menière's disease (MD) can lead to disabling vertigo attacks with hearing loss. Triple semicircular canal plugging (TSCP) surgery is a new treatment for MD, but high-quality evidence is scarce. This study aimed to assess the long-term efficacy and safety of TSCP.

Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial.

Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity.

Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.

Purpose: The purpose was to investigate combined PARP and androgen inhibition in primary prostate cancer and understand the biological mechanisms underlying clinical efficacy, especially in the absence of mutations in homologous recombination (HR) repair pathways.

Patients And Methods: The primary objective was to measure PARP inhibition, and the secondary objectives were to assess safety and feasibility. Participants received olaparib for 2 weeks before prostatectomy and were randomly assigned or not assigned (1:1) to degarelix.

A comprehensive evaluation on the associations between hearing and vision impairments and risk of all-cause and cause-specific dementia: results from cohort study, meta-analysis and Mendelian randomization study.

Background: Epidemiological studies show inconsistent links between hearing/vision impairment and dementia risk. Using multisource data, we investigated how single or combined sensory impairments relate to risks of all-cause and specific types of dementia.

Methods: We employed a triangulation approach combining three methodologies.

Sample size determination for prediction models via learning-type curves.

This article is concerned with sample size determination methodology for prediction models. We propose to combine the individual calculations via learning-type curves. We suggest two distinct ways of doing so, a deterministic skeleton of a learning curve and a Gaussian process centered upon its deterministic counterpart.

The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer.

PARTNER is a prospective, phase II-III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer, who were germline BRCA1 and BRCA2 wild type. Here we report the results of the trial. Patients (n = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin-paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery.

Global evolving patterns and cross-country inequalities of inflammatory bowel disease burden from 1990 to 2019: a worldwide report.

Aims: Inflammatory bowel disease (IBD) is a global disease. We aim to summarize the latest epidemiological patterns of IBD at the national, regional and global levels to give well-deserved attention and outline facilitating measures to reduce the disease burden.

Methods: We collected the incidence, prevalence, mortality and disability-adjusted life years (DALYs) of IBD in 204 countries and territories from 1990 to 2019 using data from the Global Burden of Disease Study 2019.

Retinal Vascular Measurements and Mortality Risk: Evidence From the UK Biobank Study.

Purpose: This study aimed to investigate the association between quantitative retinal vascular measurements and the risk of all-cause and premature mortality.

Methods: In this population-based cohort study using the UK Biobank data, we employed the Retina-based Microvascular Health Assessment System to assess fundus images for image quality and extracted 392 retinal vascular measurements per fundus image. These measurements encompass six categories of vascular features: caliber, density, length, tortuosity, branching angle, and complexity.

A randomised phase 2 study of intermittent versus continuous dosing of dabrafenib plus trametinib in patients with BRAF mutant advanced melanoma (INTERIM).

Background: BRAF+MEK inhibitors extend life expectancy of patients with BRAF mutant advanced melanoma. Acquired resistance limits duration of benefit, but preclinical and case studies suggest intermittent dosing could overcome this limitation. INTERIM was a phase 2 trial evaluating an intermittent dosing regimen.

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma.

Background: Pembrolizumab is approved for the treatment of advanced and resected melanoma and was originally licensed as a three-weekly infusion (Q3W). In April 2019, a six-weekly infusion schedule (Q6W) was also approved. We retrospectively reviewed pembrolizumab prescribing for patients with melanoma across multiple United Kingdom (UK) centres to compare the safety and efficacy of Q6W with Q3W in real-world clinical practice.

Refining the Intraoperative Identification of Suspected High-Grade Glioma Using a Surgical Fluorescence Biomarker: GALA BIDD Study Report.

Background: Improving intraoperative accuracy with a validated surgical biomarker is important because identifying high-grade areas within a glioma will aid neurosurgical decision-making and sampling.

Methods: We designed a multicentre, prospective surgical cohort study (GALA-BIDD) to validate the presence of visible fluorescence as a pragmatic intraoperative surgical biomarker of suspected high-grade disease within a tumour mass in patients undergoing 5-aminolevulinic acid (5-ALA) fluorescence-guided cytoreductive surgery.

Results: A total of 106 patients with a suspected high-grade glioma or malignant transformation of a low-grade glioma were enrolled.

Association of SCN1A, SCN2A, and UGT2B7 Polymorphisms with Responsiveness to Valproic Acid in the Treatment of Epilepsy.

Purpose: The efficacy of valproic acid (VPA) varies widely in clinical treatment of epileptic patients. Our study is aimed at exploring a potential association between polymorphisms of SCN1A, SCN2A, and UGT2B7 genetic factors and VPA responses.

Methods: In this observational study, a total of 114 epileptic patients only treated with VPA for at least 1 year were included to explore the genetic polymorphisms of drug responses (mean follow-up time: 3.

Long-term functional outcomes of hearing and speech rehabilitation efficacy among paediatric cochlear implant recipients in Shandong, China.

Purpose: To evaluate the auditory performance and speech intelligibility of 100 children with bilateral profound sensorineural hearing loss up to 3 years after cochlear implantation.

Methods: A cohort study was established consisting of 100 children who received cochlear implantation at Shandong Ear Nose and Throat Hospital from 2012 to 2015. Children were examined after 1 month, 1, 2, and 3 years of implantation to assess auditory performance and speech intelligibility using standard tools.

Trajectories of Haemoglobin and incident stroke risk: a longitudinal cohort study.

Background: Studies have demonstrated that high or low haemoglobin increases the risk of stroke. Previous studies, however, performed only a limited number of haemoglobin measurements, while there are dynamic haemoglobin changes over the course of a lifetime. This longitudinal cohort study aimed to classify the long-term trajectory of haemoglobin and examine its association with stroke incidence.

Trajectories of Lipids Profile and Incident Cardiovascular Disease Risk: A Longitudinal Cohort Study.

Background The association between low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides with cardiovascular disease (CVD) has been well studied. No previous studies considered trajectory of these lipids jointly. This study aims to characterize longitudinal trajectories of lipid profile jointly and examine its impact on incident CVD.

Small-area spatial statistical analysis of malaria clusters and hotspots in Cameroon;2000-2015.

Background: Malaria prevalence in Cameroon is a major public health problem both at the regional and urban-rural geographic scale. In 2016, an estimated 1.6 million confirmed cases, and 18,738 cases were reported in health facilities and communities respectively, with about 8000 estimated deaths.

[Association between hematocrit and risk of incident hypertension: a cohort study].

To explore the association between hematocrit level and risk of incident hypertension. Subjects who participated at least two times routine health check-up in Health Management Center of Shandong Province Hospital between January 2005 and January 2010 were eligible for inclusion. After excluding participants with known hypertension and other related diseases, a prospective cohort with 20 606 subjects (female: 8 218, male: 12 388) was established.