Flexible quantitative bias analysis for unmeasured confounding in subject-level indirect treatment comparisons with proportional hazards violation.

Background: Indirect treatment comparisons can provide evidence of relative efficacy for novel therapies when implementation of a randomised controlled trial is infeasible. However, such comparisons are vulnerable to unmeasured confounding bias due to incomplete data collection and non-random treatment assignment. Quantitative bias analysis (QBA) is a framework used to assess the sensitivity of a study's conclusions to unmeasured confounding.

The association between 25-hydroxyvitamin D and parathyroid hormone in adolescents living with HIV in southern Africa: a cross-sectional study.

Low vitamin D associated with high parathyroid hormone (PTH) is common in HIV infection. We determined the association between total 25(OH)D and PTH in adolescents living with HIV, in Zambia and Zimbabwe. Adolescents (11-19 years) perinatally infected with HIV and established on antiretroviral therapy for ≥ 6 months were recruited into a cross-sectional study.

Patterns of linear growth among children and adolescents living with HIV on antiretroviral therapy in Zimbabwe and Zambia.

Background: Adolescents with HIV (AWH) frequently exhibit impaired growth, which manifests as stunting and wasting. We studied trajectories in leg-length (appendicular), sitting (axial), and standing height among AWH on antiretroviral therapy (ART), determining peak height velocity (PHV) and age at PHV (aPHV).

Methods: Analyses used VITALITY trial data from Zimbabwe and Zambia (PACTR20200989766029), which recruited AWH (11-19 years) established on ART to determine whether vitamin D/calcium supplementation improves bone health.

The determinants of handwashing in humanitarian crisis setting during the COVID-19 pandemic: a multi-country analysis.

The Wash'Em process was developed to improve the design of handwashing behaviour change programmes during outbreaks and humanitarian crises. It aims to rapidly create evidence-based, contextualized handwashing programmes. Wash'Em was widely used during the COVID-19 pandemic.

Effects of cladribine on intrathecal and peripheral B and plasma cells.

Introduction: Cladribine is a deoxyadenosine analogue that can penetrate the blood-brain barrier. It is used to treat multiple sclerosis (MS). However, the mechanistic understanding of the effect of this highly effective therapy on B cells and plasma cells in the central nervous system compartment is limited.

The role of vitamin D metabolism in regulating bone turnover in adolescents with perinatally-acquired HIV in Southern Africa: a cross-sectional study in Zimbabwe and Zambia.

Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis, and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in Southern Africa. A pre-planned secondary analysis was performed of baseline data from the vitamin D for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology trial (PACTR20200989766029) which enrolled ALWH (11-19 yr) taking antiretroviral therapy for ≥6 mo, and recorded socio-demographic, clinical and dietary data.

Improved water supply infrastructure to reduce acute diarrhoeal diseases and cholera in Uvira, Democratic Republic of the Congo: Results and lessons learned from a pragmatic trial.

Background: Safely managed drinking water is critical to prevent diarrhoeal diseases, including cholera, but evidence on the effectiveness of piped water supply in reducing these diseases in low-income and complex emergency settings remains scarce.

Methods: We conducted a trial of water supply infrastructure improvements in Uvira (DRC). Our primary objective was to estimate the relationship between a composite index of water service quality and the monthly number of suspected cholera cases admitted to treatment facilities and, as a secondary analysis, the number of cases confirmed by rapid diagnostic tests.

Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia.

Introduction: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD).

Methods: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD-NM scale. This was assessed in 522 mutation carriers and 310 mutation-negative controls from the Genetic Frontotemporal dementia Initiative (GENFI).

Associations between Shared Sanitation, Stunting and Diarrhoea in Low-Income, High Density Urban Neighbourhoods of Maputo, Mozambique - a Cross-Sectional Study.

Introduction: Shared sanitation facilities are used by over 500 million people around the world. Most research evidence indicates that shared sanitation conveys higher risk than household sanitation for many adverse health outcomes. However, studies often fail to account for variation between different types of shared facilities.

Predicting progression to Alzheimer's disease dementia using cognitive measures.

Objectives: It is important to determine if cognitive measures identified as being prognostic in dementia research cohorts also have utility in memory clinics. We aimed to identify measures with the greatest power to predict future Alzheimer's disease (AD) dementia in a clinical setting where expensive biomarkers are not widely available.

Methods: This study utilized routine Memory Clinic data collected over 18 years.

Disease activity 4.5 years after starting cladribine: experience in 264 patients with multiple sclerosis.

Background: Cladribine is an effective immunotherapy for people with multiple sclerosis (pwMS). Whilst most pwMS do not require re-treatment following standard dosing (two treatment courses), disease activity re-emerges in others. The characteristics of pwMS developing re-emerging disease activity remain incompletely understood.

A cluster-randomised controlled equivalence trial of the Surprise Soap handwashing intervention among older children living in a refugee settlement in Sudan.

Introduction: Increasing handwashing with soap (HWWS) among older children in emergency settings can have a large public health impact, however, evidence on what works is limited. One promising approach is the 'Surprise Soap' intervention in which a novel soap with an embedded toy is delivered to children in a short, participatory household session that includes a glitter game and HWWS practice. Here, we evaluate this intervention against a standard intervention in a complex emergency setting.

Prodromal language impairment in genetic frontotemporal dementia within the GENFI cohort.

Objective: To identify whether language impairment exists presymptomatically in genetic frontotemporal dementia (FTD), and if so, the key differences between the main genetic mutation groups.

Methods: 682 participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 290 asymptomatic and 82 prodromal mutation carriers (with C9orf72, GRN, and MAPT mutations) as well as 310 mutation-negative controls. Language was assessed using items from the Progressive Aphasia Severity Scale, as well as the Boston Naming Test (BNT), modified Camel and Cactus Test (mCCT) and a category fluency task.

Effect of a novel hygiene intervention on older children's handwashing in a humanitarian setting in Kahda district, Somalia: A cluster-randomised controlled equivalence trial.

Introduction: Improving handwashing with soap (HWWS) among children in humanitarian emergencies has the potential to reduce the transmission of several important infectious diseases. However, there is limited evidence on which approaches are effective in increasing HWWS among children in humanitarian settings. One recent innovation - the "Surprise Soap" intervention - was shown to be successful in a small-scale efficacy trial in a humanitarian setting in Iraq.

High consumption of unhealthy commercial foods and beverages tracks across the complementary feeding period in rural/peri-urban Cambodia.

Consumption of unhealthy commercial foods and beverages (UCFB) is common among infants and young children living in low- and middle-income countries. Such foods can displace other nutritious foods, however, there is limited evidence on how this consumption tracks across time. This study assessed and tracked UCFB consumption of children living in rural/peri-urban Cambodia during the complementary feeding period, identified UCFB consumption patterns of these children, and explored the association between UCFB consumption and growth.

Neuropsychiatric symptoms in genetic frontotemporal dementia: developing a new module for Clinical Rating Scales.

Background: Current clinical rating scales in frontotemporal dementia (FTD) often do not incorporate neuropsychiatric features and may therefore inadequately measure disease stage.

Methods: 832 participants from the Genetic FTD Initiative (GENFI) were recruited: 522 mutation carriers and 310 mutation-negative controls. The standardised GENFI clinical questionnaire assessed the frequency and severity of 14 neuropsychiatric symptoms: visual, auditory, and tactile hallucinations, delusions, depression, anxiety, irritability/lability, agitation/aggression, euphoria/elation, aberrant motor behaviour, hypersexuality, hyperreligiosity, impaired sleep, and altered sense of humour.

Language impairment in the genetic forms of behavioural variant frontotemporal dementia.

Background: Behavioural variant fronto-temporal dementia (bvFTD) is characterised by a progressive change in personality in association with atrophy of the frontal and temporal lobes. Whilst language impairment has been described in people with bvFTD, little is currently known about the extent or type of linguistic difficulties that occur, particularly in the genetic forms.

Methods: Participants with genetic bvFTD along with healthy controls were recruited from the international multicentre Genetic FTD Initiative (GENFI).

Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales.

Objective: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD).

Methods: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands).

Predicting Cognitive Decline in Older Adults Using Baseline Metrics of AD Pathologies, Cerebrovascular Disease, and Neurodegeneration.

Background And Objectives: Dementia is a growing socioeconomic challenge that requires early intervention. Identifying biomarkers that reliably predict clinical progression early in the disease process would better aid selection of individuals for future trial participation. Here, we compared the ability of baseline, single time-point biomarkers (CSF amyloid 1-42, CSF ptau-181, white matter hyperintensities (WMH), cerebral microbleeds, whole-brain volume, and hippocampal volume) to predict decline in cognitively normal individuals who later converted to mild cognitive impairment (MCI) (CNtoMCI) and those with MCI who later converted to an Alzheimer disease (AD) diagnosis (MCItoAD).

Environmental and behavioural exposure pathways associated with diarrhoea and enteric pathogen detection in 5-month-old, periurban Kenyan infants: a cross-sectional study.

Objectives: The aim of this study was to test whether household environmental hygiene and behavioural conditions moderated associations between diarrhoea and enteric pathogen detection in infants 5 months of age in Kenya and pathogen sources, including latrine access, domestic animal co-habitation and public food sources.

Design: Cross-sectional study utilising enrolment survey data of households participating in the Safe Start cluster-randomised controlled trial .

Setting: Kisumu, Kenya.

Life course, genetic, and neuropathological associations with brain age in the 1946 British Birth Cohort: a population-based study.

Background: A neuroimaging-based biomarker termed the brain age is thought to reflect variability in the brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed to examine potential drivers and correlates of brain age.

Methods: Participants, born in a single week in 1946 in mainland Britain, have had 24 prospective waves of data collection to date, including MRI and amyloid PET imaging at approximately 70 years old.

Trajectories of early growth and subsequent lung function in cystic fibrosis: An observational study using UK and Canadian registry data.

Background: Understanding the pulmonary impact of changes in early life nutritional status over time in a paediatric CF population may help inform how to use nutritional assessment to guide clinical care. National registry data provides an opportunity to study patterns of weight gain over time at the level of the individual, and thus to gain detailed understanding of the relationship between early weight trajectories and later lung function in children with Cystic Fibrosis (CF).

Methods: Using data from the United Kingdom (UK) and Canadian CF Registries, a mixed effects linear regression model was used to describe children's weight and BMI z-score trajectories from age 1 to 5 years.

Seroconversion following COVID-19 vaccination: can we optimize protective response in CD20-treated individuals?

Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence coronavirus disease 2019 (COVID-19) severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following severe acute respiratory syndrome corona virus two (SARS-CoV-2) infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B-cell populations that may be instrumental in the control of relapsing MS.