Adverse pregnancy and perinatal outcomes (APPOs), including pre-term birth, pre-eclampsia and gestational diabetes, can result in maternal and neonatal morbidity and mortality, parental anxiety and increased healthcare costs. A better understanding of the causes of APPOs is essential to inform lifestyle and pharmaceutical interventions for their prevention and management. Given the difficulty of undertaking randomised controlled trials in pregnant women, triangulating evidence from across methods with different sources of bias may improve causal inference for APPOs. The purpose of the Mendelian randomisation in pregnancy (MR-PREG) collaboration is to support such triangulation using genetic (eg, Mendelian randomisation (MR)) and non-genetic (eg, partner negative controls) approaches to investigate the causal effects of maternal exposures on a comprehensive set of APPOs.

The MR-PREG collaboration includes individual participant data from three birth cohorts (two from the UK and one from Norway) and UK Biobank, as well as summary data from FinnGen and publicly available genome-wide association studies (GWAS). Data have been harmonised across studies and currently include information on up to 35 APPOs in up to 707 797 women.

The main aims of MR-PREG are to strengthen the evidence base for (1) prevention, by advancing understanding of maternal lifestyle factors on APPOs, (2) the role of pre-conceptional health, by improving understanding of the effect of maternal pre-existing conditions on APPOs, and (3) treatments, by evaluating the efficacy and safety of existing medications used for pre-existing conditions, and by identifying and testing novel or repurposed therapies for APPOs. To date, our published work has mainly addressed aims 1 and 3. Examples include triangulation of evidence from MR, conventional multivariable regression and paternal negative control, showing that higher maternal body mass index increases the risk of multiple APPOs, as well as the identification of maternal circulating metabolites and proteins that may influence birth weight.

Future priorities include increasing diversity within the MR-PREG collaboration by expanding representation of participants from non-European ancestries. We are also integrating molecular data, including circulating protein levels and placental transcriptomics, to better characterise the molecular mechanisms underlying APPOs. Additionally, we are using whole-exome and whole-genome sequencing to identify novel causal genes and to inform the prioritisation of candidate therapeutic targets for APPOs.

To investigate the potential long-term impacts of adult growth hormone deficiency (GHD).

Observational, retrospective matched cohort.

UK Clinical Practice Research Datalink (CPRD) Aurum database of primary care records with linkage to deprivation, secondary care and mortality data.

Adults registered with CPRD between 31/03/2002 and 29/03/2021. Individuals with GHD were exact matched up to 1:4 with unaffected controls on sex, age group (by decade) and general practice with propensity score matching on age, ethnicity and deprivation.

Mortality, cardiovascular disease (CVD), osteoporosis, fractures, depression, time off work and unemployment were investigated using Cox proportional hazards modelling.

1573 adults with GHD were matched to 6234 unaffected controls. Median follow-up was 5.2 years for cases (IQR 2.2, 10.6) and 5.1 years for controls (IQR 2.2, 10.3). Adult GHD was associated with an increased risk of premature mortality (adjusted HR (aHR) 1.61; 95% CI 1.27, 2.03), CVD (aHR 2.38; 95% CI 1.84 to 3.07) and osteoporosis (aHR 4.03; 95% CI 2.88 to 5.65), but there was no evidence for an increased risk of fractures. A higher rate of depression (aHR 1.72; 95% CI 1.23 to 2.40) and unemployment (aHR 2.06; 95% CI 1.56 to 2.71) was also seen in adults with GHD, although there was no evidence for increased time off work.

GHD in adults is associated with increased risk of premature mortality, CVD, osteoporosis, depression and socioeconomic challenges such as unemployment. Timely diagnosis, appropriate treatment and comprehensive support are critical to mitigating these adverse outcomes.

The Veterans Health Administration (VA) integrated mental and physical health services to better detect and treat depression. Primary care nurses conduct screening annually. Clinicians, including Primary Care Mental Health Integration (PCMHI) specialists, follow-up as needed for treatment. Depression detection and management processes are complex, involve multilevel stakeholders, and are subject to significant disruption from COVID-19 and from the resulting expansion of telehealth, aiming to preserve care access. This study aimed to examine whether the COVID-19 pandemic worsened depression-related care quality and/or patient outcomes (eg, suicide).

Given hypothesised care disruption (lowered care quality) during COVID-19, we will first assess the VA population’s trajectory from a new positive depression (and suicide risk) screen to appropriate treatment (ie, medication, therapy) in the Fiscal Year 2019–2323. We will also examine the changing mix of virtual and in-person depression care delivered. Second, we will use interrupted time series analyses to explore the extent to which psychiatric emergency visits and hospitalisations may be mitigated by clinician detection of depression. As well as compare mental health-related mortality rates between patients detected and not detected to have depression. Subanalyses will reveal where (eg, clinics with low PCMHI access) and for whom (eg, minorities) detection does not systematically occur, and downstream negative sequelae, to guide future intervention. Finally, we will interview 40 veterans, half of whom were detected and half not detected to have depression and 40 VA primary care and PCMHI providers about changes brought on by the pandemic and the expansion of virtual care across three VA facilities. In addition to contextualising disrupted care findings, qualitative data will help identify best practices on patient-to-provider and provider-to-provider interactions in hybrid in-person/telehealth depression care models.

Ethics approval was granted by the VA Greater Los Angeles Healthcare System Institutional Review Board. Alongside journal publications, dissemination activities include briefings to our policy and operational partners, and presentations to clinical, research and policy-oriented audiences.

Cystic fibrosis-related diabetes (CFRD) is one of the most clinically impactful comorbidities associated with cystic fibrosis (CF). Current recommended management with insulin therapy is challenging due to variable daily insulin requirements and adds to the significant burden of self-management. This study aims to determine if hybrid closed-loop insulin delivery can improve glucose outcomes compared with standard insulin therapy with continuous glucose monitoring (CGM) in young people (≥16 years) and adults with CFRD.

This open-label, multicentre, randomised, two-arm, single-period parallel design study aims to randomise 114 young people (≥16 years) and adults with CFRD. Following a 2–3 weeks’ run-in period, during which time participants use a masked CGM, participants with time in target glucose range (3.9–10.0 mmol/L) 10.0 mmol/L), mean glucose and HbA1c. Other secondary efficacy outcomes include glucose and insulin metrics, change in forced expiratory volume in 1 s and body mass index. Safety, utility, participant experiences and participant-reported outcome measures will also be evaluated. The trial is funded by the National Institute for Health and Care Research.

Ethics approval has been obtained from East of England–Cambridge South Research Ethics Committee. Results will be disseminated by peer-reviewed publications and conference presentations, and findings will be shared with people living with CF, healthcare providers and relevant stakeholders.

NCT05562492.

Inherited retinal diseases (IRDs) are a broad range of diseases associated with abnormalities/degeneration of retinal cells. We aimed to identify the top 10 Australian research priorities for IRDs to ultimately facilitate more meaningful and potentially cost-effective research.

We conducted a James Lind Alliance priority setting partnership that involved two Australian-wide surveys and online workshops.

Australia-wide.

Individuals aged 16 years or older were eligible to participate if they had an IRD, were caregivers of an individual with an IRD or were health professionals providing care to this community.

In Survey 1, we gathered participants’ unanswered questions about IRDs. We grouped these into summary questions and undertook a literature review to verify if they were truly unanswered (ie, evidence uncertainties). In Survey 2, participants voted for the uncertainties that they considered a priority. Top-ranked uncertainties progressed for discussion and final prioritisation in two workshops.

In Survey 1, we collected 223 questions from 69 participants. We grouped these into 42 summary questions and confirmed 41 as evidence uncertainties. In Survey 2, 151 participants voted, with the 16 uncertainties progressing to final prioritisation. The top 10 priorities, set by the 24 workshop participants, represented (1) treatment/cure; (2) symptoms and disease progression; (3) psychosocial well-being and (4) health service delivery. The #1 priority was for treatment to prevent, slow down or stop vision loss, followed by the #2 priority to address the psychological impact of having an IRD.

The top 10 research priorities highlight the need for IRD research that takes a whole-person, systems approach. Collaborations to progress priorities will accelerate the translation of research into real-world benefits.