Association between use of sodium-glucose co-transporter-2 inhibitor and the risk of incident dementia: a population-based cohort study.

Objectives: To assess the association between sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use and the risk of incident dementia compared with dipeptidyl peptidase-4 inhibitors (DPP-4i) use among individuals with type 2 diabetes.

Design: A population-based retrospective cohort study.

Setting: The Clinical Practice Research Datalink (CPRD) Aurum database from the UK.

Penalized G-estimation for effect modifier selection in a structural nested mean model for repeated outcomes.

Effect modification occurs when the impact of the treatment on an outcome varies based on the levels of other covariates known as effect modifiers. Modeling these effect differences is important for etiological goals and for purposes of optimizing treatment. Structural nested mean models (SNMMs) are useful causal models for estimating the potentially heterogeneous effect of a time-varying exposure on the mean of an outcome in the presence of time-varying confounding.

Impact of the COVID-19 pandemic on primary care for hypertension in the UK: a population-based cohort study.

Objectives: To describe the impact of the COVID-19 pandemic on hypertension diagnosis and management in UK primary care.

Design: Population-based cohort study.

Setting: Over 2000 general practices across the UK contributing to the Clinical Practice Research Datalink.

Molecular dissection of laboratory contamination between two schistosome populations.

Background: Genomic analysis has revealed extensive contamination among laboratory-maintained microbes including malaria parasites, Mycobacterium tuberculosis, and Salmonella spp. Here, we provide direct evidence for recent contamination of a laboratory schistosome parasite population, and we investigate its genomic consequences. The Brazilian Schistosoma mansoni population SmBRE has several distinctive phenotypes, showing poor infectivity, reduced sporocyst number, low levels of cercarial shedding and low virulence in the intermediate snail host, and low worm burden and low fecundity in the vertebrate rodent host.

PTSD Coach as an early mobile intervention to improve cancer-related anxiety and psychosocial oncology uptake in patients newly diagnosed with head and neck cancer: pilot randomized controlled trial.

Background: This pilot study aimed to provide supportive evidence for the feasibility of conducting a full-scale intervention trial with patients newly diagnosed with head and neck cancer (HNC). This included assessing the acceptability and potential usefulness of the PTSD Coach mobile app as an early self-management intervention that gives information about anxiety symptoms, offers self-assessment of symptoms with feedback, tools to self-manage anxiety, and connects to support.

Methods: A three-arm randomized controlled trial was conducted.

Metformin and risk of adverse pregnancy outcomes among pregnant women with gestational diabetes in the United Kingdom: A population-based cohort study.

Aims: Metformin is increasingly used off-label as the treatment of gestational diabetes (GDM). Our objective was to determine if metformin versus insulin initiation is associated with the adverse pregnancy outcomes.

Materials And Methods: We conducted a retrospective cohort study using data from the Clinical Practice Research Datalink, its pregnancy register, and Hospital Episode Statistics from 1998 to 2018.

Modern Sources of Controls in Case-Control Studies.

In 1992, Wacholder and colleagues developed a theoretical framework for case-control studies to minimize bias in control selection. They described three comparability principles (study base, deconfounding, and comparable accuracy) to reduce the potential for selection bias, confounding, and information bias in case-control studies. Wacholder et al.

Multimodal scanning of genetic variants with base and prime editing.

Mutational scanning connects genetic variants to phenotype, enabling the interrogation of protein functions, interactions and variant pathogenicity. However, current methodologies cannot efficiently engineer customizable sets of diverse genetic variants in endogenous loci across cellular contexts in high throughput. Here, we combine cytosine and adenine base editors and a prime editor to assess the pathogenicity of a broad spectrum of variants in the epithelial growth factor receptor gene (EGFR).

Abundant genetic variation is retained in many laboratory schistosome populations.

Schistosomes are obligately sexual blood flukes that can be maintained in the laboratory using freshwater snails as intermediate and rodents as definitive hosts. The genetic composition of laboratory schistosome populations is poorly understood: whether genetic variation has been purged due to serial inbreeding or retained is unclear. We sequenced 19 - 24 parasites from each of five laboratory populations and compared their genomes with published exome data from four field populations.

Addressing bias due to measurement error of an outcome with unknown sensitivity in database epidemiological studies.

In epidemiological database studies, the occurrence of an event is measured with error through an indicator whose specificity is often maximised, at the expense of sensitivity. However, if the indicator has low sensitivity, measures of occurrence are underestimated. In association studies, risk difference is biased, and risk ratio may be biased as well, in either direction, if the sensitivity is differential across exposure groups.

High-Risk Medications in Persons Living With Dementia: A Randomized Clinical Trial.

Importance: Individuals with Alzheimer disease (AD) and Alzheimer disease-related dementias (ADRD) may be at increased risk for adverse outcomes relating to inappropriate prescribing of certain high-risk medications, including antipsychotics, sedative-hypnotics, and strong anticholinergic agents.

Objective: To evaluate the effect of a patient/caregiver and prescriber-mailed educational intervention on potentially inappropriate prescribing to patients with AD or ADRD.

Design, Setting, And Participants: This prospective, open-label, pragmatic randomized clinical trial, embedded in 2 large national health plans, was conducted from April 2022 to June 2023.

Engineered allogeneic T cells decoupling T-cell-receptor and CD3 signalling enhance the antitumour activity of bispecific antibodies.

Bispecific antibodies (biAbs) used in cancer immunotherapies rely on functional autologous T cells, which are often damaged and depleted in patients with haematological malignancies and in other immunocompromised patients. The adoptive transfer of allogeneic T cells from healthy donors can enhance the efficacy of biAbs, but donor T cells binding to host-cell antigens cause an unwanted alloreactive response. Here we show that allogeneic T cells engineered with a T-cell receptor that does not convert antigen binding into cluster of differentiation 3 (CD3) signalling decouples antigen-mediated T-cell activation from T-cell cytotoxicity while preserving the surface expression of the T-cell-receptor-CD3 signalling complex as well as biAb-mediated CD3 signalling and T-cell activation.

Development of a Canadian Guidance for reporting real-world evidence for regulatory and health-technology assessment (HTA) decision-making.

Background And Objective: Real-world evidence (RWE) can complement and fill knowledge gaps from randomized controlled trials to assist in health-technology assessment (HTA) for regulatory decision-making. However, the generation of RWE is an intricate process with many sequential decision points, and different methods and approaches may impact the quality and reliability of evidence. Standardization and transparency in reporting these decisions is imperative to appraise RWE and incorporate it into HTA decision-making.

Exposure to Valsartan Products Containing Nitrosamine Impurities in the United States, Canada, and Denmark.

Background: Following the mass recall of valsartan products with nitrosamine impurities in July 2018, the number of patients exposed to these products, the duration of exposure, and the potential for cancer remains unknown. Therefore, we assessed the extent and duration of use of valsartan products with a nitrosamine impurity in the United States, Canada, and Denmark.

Methods: We conducted a retrospective cohort study using administrative healthcare data from the US FDA Sentinel System, four Canadian provinces that contribute to the Canadian Network for Observational Drug Effect Studies (CNODES), and the Danish National Prescription Registry.

Mothers and Babies Virtual Group (MBVG) for perinatal Latina women: study protocol for a hybrid type-1 effectiveness-implementation randomized controlled trial.

Background: Immigrant Latinas (who are foreign-born but now reside in the USA) are at greater risk for developing postpartum depression than the general perinatal population, but many face barriers to treatment. To address these barriers, we adapted the Mothers and Babies Course-an evidence-based intervention for postpartum depression prevention-to a virtual group format. Additional adaptations are inclusion of tailored supplemental child health content and nutrition benefit assistance.

Molecular programs guiding arealization of descending cortical pathways.

Layer 5 extratelencephalic (ET) neurons are present across neocortical areas and send axons to multiple subcortical targets. Two cardinal subtypes exist: (1) Slco2a1-expressing neurons (ET), which predominate in the motor cortex and project distally to the pons, medulla and spinal cord; and (2) Nprs1- or Hpgd-expressing neurons (ET), which predominate in the visual cortex and project more proximally to the pons and thalamus. An understanding of how area-specific ET and ET emerge during development is important because they are critical for fine motor skills and are susceptible to spinal cord injury and amyotrophic lateral sclerosis.

Microbes and metabolites in immunity.

The immune system has a vital, albeit complex, relationship with the microbes residing within us, one that we are only beginning to understand. We asked investigators what they felt were the fundamental challenges we currently face in unraveling the impacts of microbes and their metabolites on host immunity and to discuss key opportunities toward achieving future insights and innovation.