Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice.

Purpose: As part of the 100,000 Genomes Project, we set out to assess the potential viability and clinical impact of reporting genetic variants associated with drug-induced toxicity for patients with cancer recruited for whole-genome sequencing (WGS) as part of a genomic medicine service.

Methods: Germline WGS from 76,805 participants was analyzed for pharmacogenetic (PGx) variants in four genes (, , , ) associated with toxicity induced by five drugs used in cancer treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking genomic data with prescribing and hospital incidence records, a phenome-wide association study (PheWAS) was performed to identify whether phenotypes indicative of adverse drug reactions (ADRs) were enriched in drug-exposed individuals with the relevant PGx variants.

Public health management of pertussis in adults: Practical challenges and future strategies.

A panel of 24 international experts met in July 2022 to discuss challenges associated with pertussis detection, monitoring, and vaccination in adults; conclusions from this meeting are presented. There has been a shift in the epidemiology of pertussis toward older children and adults. This shift has been attributed to the waning of infection- or vaccine-induced immunity, newer detection techniques causing detection bias, and possibly the replacement of whole-cell pertussis with acellular vaccines in high-income countries, which may lead to immunity waning more quickly.

Expression of Dystrophin Dp71 Splice Variants Is Temporally Regulated During Rodent Brain Development.

Dystrophin Dp71 is the major product of the Duchenne muscular dystrophy (DMD) gene in the brain, and its loss in DMD patients and mouse models leads to cognitive impairments. Dp71 is expressed as a range of proteins generated by alternative splicing of exons 71 to 74 and 78, classified in the main Dp71d and Dp71f groups that contain specific C-terminal ends. However, it is unknown whether each isoform has a specific role in distinct cell types, brain regions, and/or stages of brain development.

Features and behaviours for weight loss in the Chilean cohort with obesity from the ACTION study.

In Latin America, obesity rates are among the highest in the world. Currently, people with obesity (PWO) receive suboptimal care due to several challenges and barriers. The international ACTION-IO study aimed to identify perceptions, attitudes and behaviours of PWO and healthcare providers (HCP), and to assess potential barriers to effective obesity care.

AAV-Mediated Restoration of Dystrophin-Dp71 in the Brain of Dp71-Null Mice: Molecular, Cellular and Behavioral Outcomes.

A deficiency in the shortest dystrophin-gene product, Dp71, is a pivotal aggravating factor for intellectual disabilities in Duchenne muscular dystrophy (DMD). Recent advances in preclinical research have achieved some success in compensating both muscle and brain dysfunctions associated with DMD, notably using exon skipping strategies. However, this has not been studied for distal mutations in the gene leading to Dp71 loss.

An Online Decision Aid for Patients With Metastatic Melanoma—Results of the Randomized Controlled Trial “PEF-Immun”.

Background: Treatment decisions in metastatic melanoma (MM) are highly dependent on patient preferences and require the patients' involvement. The complexity of treatment options with their individual advantages and disadvantages is often overwhelming. We therefore developed an online patient decision aid (PtDA) to facilitate shared decision making (SDM).

Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme.

The Cancer Programme of the 100,000 Genomes Project was an initiative to provide whole-genome sequencing (WGS) for patients with cancer, evaluating opportunities for precision cancer care within the UK National Healthcare System (NHS). Genomics England, alongside NHS England, analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types.

Clinical Evaluation of a Hydrophobic Intraocular Lens Using a Preloaded Automated Injector in a Korean Population.

Purpose: This study assessed post-market clinical outcomes of the Clareon monofocal intraocular lens (IOL) preloaded in the AutonoMe Delivery System in a real-world setting of Korean patients.

Methods: This prospective, multicenter, single-arm study in Korea was conducted from July 2020 to December 2021. Patients were ≥20 years old with unilateral or bilateral cataracts who received Clareon IOLs (CNA0T0) preloaded in an automated injector system.

Patient-reported outcome measures after periodontal surgery.

Objectives: The present study aimed to explore the impact of different periodontal surgical treatments on the quality of life and postoperative morbidity.

Materials And Methods: The present study is a single-center, prospective, observational cohort trial. One hundred fifty-five patients, referred to the Periodontal Department of Bologna University who needed periodontal surgical treatment, were recruited.

Comparison of CD4+/CD8+ Lymphocytic Subpopulations Pre- and Post-Antituberculosis Treatment in Patients with Diabetes and Tuberculosis.

Is there a CD4+ and CD8+ immunity alteration in patients with pulmonary tuberculosis (TB) and diabetes (DM) that does not recover after antituberculosis treatment? This prospective comparative study evaluated CD4+ and CD8+ lymphocytic subpopulations and antituberculosis antibodies in patients with diabetes and tuberculosis (TB-DM), before and after antituberculosis treatment. CD4+ T cell counts were lower in patients with TB-DM compared to those with only TB or only DM, and these levels remained low even after two months of anti-TB treatment. Regarding the CD8+ T cell analysis, we identified higher blood values in the DM-only group, which may be explained by the high prevalence of latent tuberculosis (LTBI) in patients with DM.

Association between weight loss and health care resource utilization in adults living with obesity: Evidence from a UK primary care database.

Aims: We investigated the impact of intentional weight loss on health care resource utilization (HCRU) and costs among people with obesity.

Materials And Methods: This retrospective, observational cohort study used data from the Clinical Practice Research Datalink (CPRD) GOLD database. Adults >18 years at index date [first recorded body mass index (BMI) of 30-50 kg/m between 2006 and 2015 with a further BMI record 4 years later] were assigned to an intentional weight loss cohort (-25% to -10% BMI change) or a stable weight cohort (-3% to +3%), based on their BMI change during a 4-year baseline period from index date.

DElaying Disease Progression In COPD with Early Initiation of Dual Bronchodilator or Triple Inhaled PharmacoTherapy (DEPICT): A Predictive Modelling Approach.

Introduction: Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade 2) versus severe and very severe COPD (GOLD grades 3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD.

Methods: The modelling approach used data on decline in forced expiratory volume in 1 s (FEV) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy.

Avoiding errors and complications related to immediate implant placement in the esthetic area with a mucogingival approach.

Immediate implant placement is considered the treatment of choice for single tooth replacement in the esthetic area. However, this treatment is associated with several critical drawbacks related to the inadequate assessment/management of the soft and hard peri-implant tissues and their subsequent remodeling, resulting in peri-implant soft-tissue defects that can lead to impaired esthetic outcomes in time. We describe in detail how the mucogingival approach to immediate implant placement ensures a standard result regardless of the baseline soft-hard tissue situation.

Clinical standards for the management of adverse effects during treatment for TB.

Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE. 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.

Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease.

Background And Aims: Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD.

Methods: The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin.