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OBJECTIVE: To investigate Covid-19 vaccination as a potential secondary public health benefit of case management for Medicaid beneficiaries with health and social needs. DATA SOURCES AND STUDY SETTING: The CommunityConnect case management program for Medicaid beneficiaries is run by Contra Costa Health, a county safety net health system in California. Program enrollment data were merged with comprehensive county vaccination records. STUDY DESIGN: Individuals with elevated risk of hospital and emergency department use were randomized each month to a case management intervention or usual care. Interdisciplinary case managers offered coaching, community referrals, healthcare connections, and other support based on enrollee interest and need. Using survival analysis with intent-to-treat assignment, we assessed rates of first-dose Covid-19 vaccination from December 2020 to September 2021. In exploratory sub-analyses we also examined effect heterogeneity by gender, race/ethnicity, age, and primary language. DATA COLLECTION AND EXTRACTION METHODS: Data were extracted from county and program records as of September 2021, totaling 12,866 interventions and 25,761 control enrollments. PRINCIPAL FINDINGS: Approximately 58% of enrollees were female and 41% were under age 35. Enrollees were 23% White, 12% Asian/Pacific Islander, 20% Black/African American, and 36% Hispanic/Latino, and 10% other/unknown. Approximately 35% of the intervention group engaged with their case manager. Approximately 56% of all intervention and control enrollees were vaccinated after 9 months of analysis time. Intervention enrollees had a higher vaccination rate compared to control enrollees (adjusted hazard ratio [aHR]: 1.06; 95% confidence interval [CI]: 1.02-1.10). In sub-analyses, the intervention was associated with stronger likelihood of vaccination among males and individuals under age 35. CONCLUSIONS: Case management infrastructure modestly improved Covid-19 vaccine uptake in a population of Medicaid beneficiaries that over-represents social groups with barriers to early Covid-19 vaccination. Amidst mixed evidence on vaccination-specific incentives, leveraging trusted case managers and existing case management programs may be a valuable prevention strategy.

ImportanceHousing deposits and tenancy supports have become new Medicaid benefits in multiple states; however, evidence on impacts from these specific housing interventions is limited.ObjectiveTo evaluate the association of rental housing deposits and health care use among Medicaid beneficiaries receiving social needs case management as part of a Whole-Person Care (Medicaid 1115 waiver) pilot program in California.Design, setting, and participantsThis cohort study compared changes in health care use among a group of adults who received a housing deposit between October 2018 and December 2021 along with case management vs a matched comparison group who received case management only in Contra Costa County, California, a large county in the San Francisco Bay Area. All participants were enrolled in health and social needs case management based on elevated risk of acute care use. Data analysis took place from March 2023 to June 2024.ExposureRental housing deposit funds that covered 1-time moving transition costs. Funds averaged $1750 per recipient.Main outcomes and measuresChanges in hospitalizations, emergency department visits, primary care visits, specialty care visits, behavioral health visits, psychiatric emergency services, or detention intakes during the 6 months before vs 6 months after deposit receipt. Changes 12 months before and after deposit receipt were examined as a sensitivity analysis.ResultsOf 1690 case management participants, 845 received a housing deposit (362 [42.8%]

Significant human gut microbiome changes during adolescence suggest that microbial community evolution occurs throughout important developmental periods including the transition to college, a typical life phase of weight gain. In this observational longitudinal study of 139 college freshmen living in on-campus dormitories, we tracked changes in the gut microbiome via 16S amplicon sequencing and body weight across a single academic year. Participants were grouped by weight change categories of gain (WG), loss (WL), and maintenance (WM). Upon assessment of the community structure, unweighted and weighted UniFrac metrics revealed significant shifts with substantial variation explained by individual effects within weight change categories. Genera that positively contributed to these associations with weight change included Bacteroides, Blautia, and Bifidobacterium in WG participants and Prevotella and Faecalibacterium in WL and WM participants. Moreover, the Prevotella/Bacteroides ratio was significantly different by weight change category, with WL participants displaying an increased ratio. Importantly, these genera did not display co-dominance nor ease of transition between Prevotella- and Bacteroides-dominated states. We further assessed the overall taxonomic variation, noting the increased stability of the WL compared to the WG microbiome. Finally, we found 30 latent community structures within the microbiome with significant associations with waist circumference, sleep, and dietary factors, with alcohol consumption chief among them. Our findings highlight the high level of individual variation and the importance of initial gut microbiome community structure in college students during a period of major lifestyle changes. Further work is needed to confirm these findings and explore mechanistic relationships between gut microbes and weight change in free-living individuals.

BACKGROUND: Identifying community characteristics associated with firearm assault could facilitate prevention. We investigated the effect of community firearm dealer and alcohol outlet densities on individual risk of firearm assault injury. METHODS: In this density-sampled case-control study of Californians, January 2005-September 2015, cases comprised all residents with a fatal or nonfatal firearm assault injury. For each month, we sampled controls from the state population in a 4:1 ratio with cases. Exposures were monthly densities of county-level pawn and nonpawn firearm dealers and ZIP code-level off-premises alcohol outlets and bars and pubs (bars/pubs). We used case-control-weighted G-computation to estimate risk differences (RD) statewide and among younger Black men, comparing observed exposure densities to hypothetical interventions setting these densities to low. We estimated additive interactions between firearm and alcohol retailer density. Secondary analyses examined interventions targeted to high exposure density or outcome burden areas. RESULTS: There were 67,850 cases and 268,122 controls. Observed (vs. low) densities of pawn firearm dealers and off-premises alcohol outlets were individually associated with elevated monthly risk of firearm assault per 100,000 people (RD pawn dealers : 0.06, 95% CI: 0.05, 0.08; RD off-premises outlets : 0.01, 95% CI: 0.01, 0.03), but nonpawn firearm dealer and bar/pub density were not; models targeting only areas with the highest outcome burden were similar. Among younger Black men, estimates were larger. There was no interaction between firearm and alcohol retailer density. CONCLUSIONS: Our results are consistent with the hypothesis that limiting pawn firearm dealers and off-premises alcohol outlet densities can reduce interpersonal firearm violence.

Abstract Binding-activated optical sensors are powerful tools for imaging, diagnostics, and biomolecular sensing. However, biosensor discovery is slow and requires tedious steps in rational design, screening, and characterization. Here we report on a platform that streamlines biosensor discovery and unlocks directed nanosensor evolution through genetically encodable fluorogenic amino acids (FgAAs). Building on the classical knowledge-based semisynthetic approach, we engineer ~15 kDa nanosensors that recognize specific proteins, peptides, and small molecules with up to 100-fold fluorescence increases and subsecond kinetics, allowing real-time and wash-free target sensing and live-cell bioimaging. An optimized genetic code expansion chemistry with FgAAs further enables rapid (~3 h) ribosomal nanosensor discovery via the cell-free translation of hundreds of candidates in parallel and directed nanosensor evolution with improved variant-specific sensitivities (up to ~250-fold) for SARS-CoV-2 antigens. Altogether, this platform could accelerate the discovery of fluorogenic nanosensors and pave the way to modify proteins with other non-standard functionalities for diverse applications.

IntroductionContinuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative.MethodsThe Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, association of fluid balance and timing of CRRT initiation, and CRRT prescription with outcomes.ResultsWe included children (n = 996, 0-25 years) admitted to an intensive care unit (ICU) and treated with CRRT for AKI or FO at 32 centers (in 7 countries) from 2018 to 2021. Demographics and clinical characteristics before CRRT initiation, during the first 7 days of both CRRT, and liberation were collected. Outcomes include the following: (i) major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction), and (ii) functional outcomes (functional stats scale).ConclusionThe retrospective WE-ROCK study represents the largest international registry of children receiving CRRT for AKI or FO. It will serve as a broad and invaluable resource for the field of pediatric critical care nephrology that will improve our understanding of practice heterogeneity and the association of CRRT with clinical and patient-centered outcomes. This will generate preliminary data for future interventional trials in this area.

Respondent-driven sampling (RDS) is a potential strategy for addressing challenges in accurate estimation of abortion incidence, but it relies on often untested assumptions. We conducted an RDS study to estimate the cumulative lifetime incidence of abortion in Soweto, Johannesburg, South Africa (April-December 2018), to evaluate whether RDS assumptions were met, and to compare RDS estimates of incidence with estimates adjusted for employment and age based on census data. A total of 849 participants were recruited from 11 seed participants between April and December 2018. The assumption that individuals can identify target population members and the assumption of approximation of sampling with replacement was met. There were minor violations of the assumptions of seed independence from the final sample and reciprocity of ties. Assumptions of accurate degree reporting and random recruitment were not met. Failure to meet assumptions yielded a study sample with different employment characteristics than those of the target population; this could not be resolved by standard RDS methods. The RDS estimate of cumulative lifetime abortion incidence was 12.1% (95% confidence interval: 9.8, 14.3), and the employment-adjusted estimate was 16.9% (95% confidence interval: 12.8, 22.1). We caution researchers in using RDS for representative estimates of abortion incidence. Use of postsurvey weights to adjust for differences in characteristics between the sample and the target population may yield more representative results.

Using individuals' genetic data researchers can generate Polygenic Scores (PS) that are able to predict risk for diseases, variability in different behaviors as well as anthropomorphic measures. This is achieved by leveraging models learned from previously published large Genome-Wide Association Studies (GWASs) associating locations in the genome with a phenotype of interest. Previous GWASs have predominantly been performed in European ancestry individuals. This is of concern as PS generated in samples with a different ancestry to the original training GWAS have been shown to have lower performance and limited portability, and many efforts are now underway to collect genetic databases on individuals of diverse ancestries. In this study, we compare multiple methods of generating PS, including pruning and thresholding and Bayesian continuous shrinkage models, to determine which of them is best able to overcome these limitations. To do this we use the ABCD Study, a longitudinal cohort with deep phenotyping on individuals of diverse ancestry. We generate PS for anthropometric and psychiatric phenotypes using previously published GWAS summary statistics and examine their performance in three subsamples of ABCD: African ancestry individuals (n = 811), European ancestry Individuals (n = 6703), and admixed ancestry individuals (n = 3664). We find that the single ancestry continuous shrinkage method, PRScs (CS), and the multi ancestry meta method, PRScsx Meta (CSx Meta), show the best performance across ancestries and phenotypes.

Tropical cyclones models have long used nesting to achieve higher resolution of the inner core than was feasible for entire model domains. These high resolution nests have been shown to better capture storm structures and improve forecast accuracy. The Hurricane Analysis and Forecast System (HAFS) is the new-generation numerical model embedded within NOAA’s Unified Forecast System (UFS). The document highlights the importance of high horizontal resolution (2 km or finer) in accurately simulating the small-scale features of tropical cyclones, such as the eyewall and eye. To meet this need, HAFS was developed by NOAA leveraging a high-resolution, storm-following nest. This nest moves with the cyclone, allowing better representation of small-scale features and more accurate feedback between the cyclone’s inner core and the larger environment. This hurricane following nest capability, implemented in the Finite-Volume Cubed-Sphere (FV3) dynamical core within the UFS framework, can be run both within the regional as well as global forecast systems. A regional version of HAFS with a single moving nest went into operations in 2023. HAFS also includes the first ever moving nest implemented within a global model which is currently being used for research. In this document we provide details of the implementation of moving nests and provide some of the results from both global and regional simulations. For the first time NOAA P3 flight data was used to evaluate the inner core structure from the global run.

IntroductionThe veterinary yearling pre-sale repository radiographs have the potential to impact both vendor and prospective purchaser. The primary aim of this study was to determine inter-observer agreement for orthopaedic lesions identified in thoroughbred yearling repository radiographs. A secondary goal was to determine agreement when using a pre-defined risk rating classification.MethodsThree experienced specialist equine surgeons (2 ACVS & 1 FANZCVS) interpreted thirty repository radiographs once each for radiographic abnormalities. Each radiographic abnormality was given an associated risk assessment for future racing performance.ResultsThe use of a pre-defined risk rating grading scale resulted in good to excellent agreement as observers reached a consensus on risk ratings for lesions 97.1% of the time. The highest agreement was for the proximal interphalangeal joint and distal interphalangeal joint, with 99.9 and 98.2% agreement, respectively. The tarsal region was the joint with the highest disagreement with respect to pathology, with observers disagreeing 5.2% of the time.DiscussionThis study found that experienced veterinary surgeons reliably agreed on the absence of lesions but showed disagreement on the specific risk rating of common lesions.

OBJECTIVES:. Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults. DESIGN:. Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study. SETTING:. Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021. PATIENTS/SUBJECTS:. Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1–2), and late (days 3–7). INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20–2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17–6.11; p = 0.02) compared with early initiation. CONCLUSIONS:. Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin.

Radiographs underestimate the extent of bone injury in horses with third carpal bone (C3) fractures (Fx). We aimed to describe bone pathologies identified using computed tomography (CT) and compare the diagnostic value of digital radiography (DR) and CT in horses with C3 Fx. CT images of 15 racehorses with C3 Fx and 10 controls were reviewed (Part 1) then DR and CT images of 26 racehorses (24 Thoroughbred, 2 Standardbred) with C3 Fx (Part 2) were evaluated. Agreement on fracture geometry and concomitant bone lesions was tested between DR and CT using the kappa statistic (Part 2). For agreement analysis, 38 limbs were used (27 Fx carpi from 26 horses and 11 contralateral carpi). Intermodality agreement was good for recognition of displacement, fair for comminution, articular surface bone loss and osseous fragmentation, and poor-slight for recognition of whether the Fx was complete, additional fissures and lucencies. CT provides more detailed information than DR regarding bone pathology and fracture configuration in horses with C3 fracture. Correlation of CT findings with clinical information and outcome needs to be explored; however, the more accurate diagnosis possible with CT is likely valuable when deciding on the most appropriate management and for surgical planning.

Interest in using internet search data, such as that from the Google Health Trends Application Programming Interface (GHT-API), to measure epidemiologically relevant exposures or health outcomes is growing due to their accessibility and timeliness. Researchers enter search term(s), geography, and time period, and the GHT-API returns a scaled probability of that search term, given all searches within the specified geographic-time period. In this study, we detailed a method for using these data to measure a construct of interest in 5 iterative steps: first, identify phrases the target population may use to search for the construct of interest; second, refine candidate search phrases with incognito Google searches to improve sensitivity and specificity; third, craft the GHT-API search term(s) by combining the refined phrases; fourth, test search volume and choose geographic and temporal scales; and fifth, retrieve and average multiple samples to stabilize estimates and address missingness. An optional sixth step involves accounting for changes in total search volume by normalizing. We present a case study examining weekly state-level child abuse searches in the United States during the coronavirus disease 2019 pandemic (January 2018 to August 2020) as an application of this method and describe limitations.

Abstract Introduction Patients with hormone receptor positive breast cancer are recommended at least five years of adjuvant endocrine therapy, but adherence to this treatment is often suboptimal. We investigated longitudinal trends in adjuvant endocrine therapy (AET) adherence among premenopausal breast cancer patients and identified clinical characteristics, including baseline comorbidities and non-cancer chronic medication use, associated with AET adherence. Methods We included stage I–III premenopausal breast cancer patients diagnosed during 2002–2011 and registered in the Danish Breast Cancer Group clinical database who initiated AET. We used group-based trajectory modeling to describe AET adherence patterns. We also linked patients to Danish population-based registries and fit multinomial logistic models to compute odds ratios (ORs) and 95% confidence intervals (95% CIs) associating clinical characteristics with AET adherence patterns. Results We identified three adherence patterns among 4,353 women—high adherers (57%), slow decliners (36%), and rapid decliners (6.9%). Women with stage I disease (vs. stage II; OR: 1.9, 95% CI 1.5, 2.5), without chemotherapy (vs. chemotherapy; OR: 4.3, 95% CI 3.0, 6.1), with prevalent comorbid disease (Charlson Comorbidity Index score ≥ 1 vs. 0; OR: 1.6, 95% CI 1.1, 2.3), and with a history of chronic non-cancer medication use (vs. none; OR: 1.3, 95% CI 1.0, 1.8) were more likely to be rapid decliners compared with high adherers. Conclusions Women with stage I cancer, no chemotherapy, higher comorbidity burden, and history of chronic non-cancer medication use were less likely to adhere to AET. Taking steps to promote adherence in these groups of women may reduce their risk of recurrence.

Abstract Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under‐construction proton therapy facility in Adelaide, other potential proton centres and an under‐evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide‐ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

In 2011, a historic Supreme Court decision mandated that the state of California substantially reduce its prison population to alleviate overcrowding, which was deemed so severe as to preclude the provision of adequate healthcare. To comply, California passed the Public Safety Realignment Act (Assembly Bill [AB] 109), representing the largest ever court-ordered reduction of a prison population in U.S. history. AB109 was successful in reducing the state prison population; however, although the policy was precipitated by inadequate healthcare in state prisons, no studies have examined its effects on prisoner health. As other states grapple with overcrowded prisons and look to Californias experience with this landmark policy, understanding how it may have impacted prisoner health is critical. We sought to evaluate the effects of AB109 on prison mortality and assess the extent to which policy-induced changes in the age distribution of prisoners may have contributed to these effects. To do so, we used prison mortality data from the Bureau of Justice Statistics and the California Deaths in Custody reporting program and prison population data from the National Corrections Reporting Program to examine changes in overall prison mortality, the age distribution of prisoners, and age-adjusted prison mortality in California relative to other states before and after the implementation of AB109. Following AB109, California prisons experienced an increase in overall mortality relative to other states that attenuated within three years. Over the same period, California experienced a greater upward shift in the age distribution of its prisoners relative to other states, suggesting that the states increase in overall mortality may have been driven by this change in age distribution. Indeed, when accounting for this differential change in age distribution, mortality among California prisoners exhibited a greater reduction relative to other states in the third year after implementation. As other states seek to reduce their prison populations to address overcrowding, assessments of Californias experience with AB109 should consider this potential improvement in age-adjusted mortality.

Firearm availability has been linked to firearm self-harm, but the joint relationship with alcohol availability, while supported by theory, has not been examined. This study sought to quantify the separate and joint relations of community firearm and alcohol availability with individual-level risk of (fatal and nonfatal) firearm self-harm. We conducted a case-control study of California residents, 2005-2015, using statewide mortality, hospital, firearm transfer, and alcohol license data. We estimated monthly marginal risk differences per 100,000 in the overall population and in white men aged 50+ under various hypothetical changes to firearm and alcohol availability and assessed additive interactions using case-control-weighted g-computation. In the overall population, non-pawn shop firearm dealer density was associated with firearm self-harm (RD: 0.02, 95% CI: 0.003, 0.04) but pawn shop firearm dealer and alcohol outlet densities were not. Secondary analyses revealed a relationship between firearm sales density and firearm self-harm (RD: 0.07, 95% CI: 0.04, 0.10). There were no additive interactions between measures of firearm and alcohol availability. Among older white men, generally the same exposures were related to self-harm as in the overall population, but point estimates were substantially larger. Findings suggest community-level approaches to reducing firearm sales may help mitigate suicide risk.

Background: Antimicrobial stewardship programs rely heavily on the electronic medical record (EMR) to carry out daily activities, make interventions, optimize patient care, and collect data. In 2019 the University of Vermont Medical Center transitioned from using a third party platform to the Epic (Verona, WI, www.epic.com) Bugsy module for antimicrobial stewardship. Method: We have spent the past 4 years optimizing the Epic foundation to match our institutional antimicrobial prescribing guidelines, susceptibility patterns, and build reports to extract actionable data. Result: During the build process, we readily identified three areas needed for customization: (1) Empiric, definitive, and prophylactic indications of use for all antimicrobials based on our hospital’s internally published books “Guide to Antimicrobial Therapy for Adults” and “Guide to Antimicrobial Therapy for Pediatrics” (figure 1); (2) An on-demand report to capture all patients with new administrations of antimicrobials in the preceding 72 hours, that includes ordering clinician, stop date of therapy, and indication (figure 2); and (3) A unique, custom-built slicer-dicer report to capture high-level data on how each antimicrobial is being prescribed by indication, dose, route of administration, ordering clinician, attending physician, and department (figure 3). Conclusion: We have built a system where we can readily identify patients that are receiving antimicrobials both within and outside of institutional guidelines and know the ordering clinician to contact to provide in-the-moment feedback. We can also collect retrospective data to know which antimicrobial agents were prescribed for all infectious syndromes. These three institutional customizations have provided invaluable information to improve patient care.

Background Breastfeeding impacts positively on multiple health outcomes, but < 50% of UK women breastfeed at 8 weeks. Women with long-term conditions face additional challenges in breastfeeding. Objectives To synthesise global and UK evidence to co-create an implementation and evaluation toolkit for cost-effective breastfeeding support in the NHS. Design Evidence syntheses with stakeholder engagement. Review methods Systematic reviews examined effectiveness of breastfeeding support for (1) healthy women and (2) women with long-term conditions using Cochrane Pregnancy and Childbirth Group methods. Mixed-methods systematic reviews synthesised process evaluations of effective breastfeeding support interventions for healthy women and experiences of receiving/providing support for breastfeeding women with long-term conditions. Cross-study synthesis integrated qualitative and quantitative findings. Systematic reviews synthesised evidence on the incremental costs and cost-effectiveness of breastfeeding support following National Institute for Health and Care Excellence guidance. All searches were conducted from May 2021 to October 2022. Stakeholder engagement and toolkit development comprised online discussions, a modified Delphi study, focus groups and four workshops. Participants were 23 stakeholders, 16 parents in the parents’ panels, 15 women in the focus groups and 87 stakeholders who attended the workshops. Results We found considerably more interventions designed for healthy women (review 1) than aimed at women with long-term conditions (reviews 1 and 4); approximately half of the studies were targeted at groups at higher risk of poor breastfeeding outcomes, and the impact of support may be different in these populations. Despite this, studies from review 2 found that women perceived the provision of support as positive, important and needed. Studies from review 5 echoed a range of suggestions from participants regarding potential strategies to improve breastfeeding support, with the most widely reported being the need to acknowledge the role and influence of other sources of support (e.g. partners, family, friends, peers, external professionals, web-based resources) and involving these sources in the provision of breastfeeding support for women with long-term conditions. In reviews 3 and 6, there was uncertainty about the cost-effectiveness of breastfeeding support interventions due to the limited number of studies and lack of good-quality evidence. Limitations There was a lack of evidence for the effectiveness and cost-effectiveness of breastfeeding interventions in the UK. There was often insufficient information reported about intervention characteristics. Conclusions ‘Breastfeeding only’ support probably reduces the number of women stopping any or exclusive breastfeeding. The evidence for ‘breastfeeding plus’ interventions is less consistent, but these may reduce the number of women stopping exclusive breastfeeding at 4–6 weeks and at 6 months. We found no evidence of differential intervention effects regarding mode of provision or provider. Cost-effectiveness is uncertain due to the lack of good-quality evidence. Key enablers of successful implementation were responsiveness and tailoring of interventions to both women’s and supporters’ needs. Breastfeeding support as delivered in the included studies probably has little to no effect on breastfeeding outcomes for women with long-term conditions. The mixed-methods synthesis and stakeholder work identified that existing interventions may not address the complex needs of these women. The main study output is a co-produced toolkit to guide implementation and evaluation of breastfeeding support services in the UK. Future work Evaluation of breastfeeding support for all women, particularly those at risk of poor breastfeeding outcomes (e.g. long-term conditions, deprivation). This could involve tailoring the toolkit to local contexts via implementation and effectiveness studies or using quality improvement studies. Study registration This study is registered as PROSPERO CRD42022337239, CRD42021229769 and CRD42022374509. The reviews of economic evidence were not registered; however, the review protocol can be accessed via the repository held by Queen’s University Belfast Research Portal (https://pure.qub.ac.uk/). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130995) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 20. See the NIHR Funding and Awards website for further award information. Plain language summary What was the question? We know that breastfeeding is good for the health of mothers and babies, yet many mothers experience difficulties and stop breastfeeding before they want to. This is noticeable among women living in disadvantaged areas where there are low rates of breastfeeding. Good support may help women overcome difficulties so that they can continue to breastfeed. Women with chronic illnesses such as diabetes and depression face additional challenges in breastfeeding. We wanted to understand how to improve breastfeeding support for UK women. What did we do? We brought together previous scientific studies to learn about what works. We also spoke with parents and service providers. We combined all our findings into a toolkit to help the NHS improve breastfeeding support for women. What did we find? We found that, for healthy women, some forms of breastfeeding support can probably help reduce the number of women stopping breastfeeding and help them breastfeed exclusively. For women with chronic illnesses, we found that the types of support used in the studies probably did not help women to breastfeed. Most of the evidence did not come from the UK. We identified barriers to providing breastfeeding support for all women, especially those who are disadvantaged. We identified strategies that could help the NHS overcome these barriers. There was a lack of evidence on how cost-effective these interventions are compared with usual care, but parents and providers saw the value of paying for breastfeeding support. What does this mean? Giving women targeted breastfeeding support will help them to breastfeed; however, we need to test if this support works in the NHS. We also need to develop additional services for women with chronic illnesses. The NHS could use our findings to improve support for all breastfeeding women by identifying specific barriers and using evidence-based strategies to overcome them. Scientific summary Background Breastfeeding impacts positively on multiple health outcomes across the lifespan. Global and UK infant recommendations are that infants should receive breastmilk exclusively for 6 months and as part of a mixed diet until 2 years. However, fewer than half of UK women are breastfeeding at 6–8 weeks, with a marked social gradient. Objectives This study aimed to synthesise global and UK evidence in order to co-create with stakeholders a framework to guide the implementation and evaluation of cost-effective breastfeeding support interventions in the NHS: Update the Cochrane review ‘Support for healthy breastfeeding mothers with healthy term babies’ (McFadden A, Gavine A, Renfrew MJ, Wade A, Buchanan P, Taylor JL, et al. Support for healthy breastfeeding mothers with healthy term babies. Cochrane Database Syst Rev 2017;2:CD001141). Synthesise process evaluations of breastfeeding support interventions. Conduct an economic evaluation of interventions to enable women to breastfeed. Conduct a systematic review of breastfeeding support interventions for women with long-term conditions (LTCs). Synthesise evidence of barriers to and facilitators of breastfeeding support for women with LTCs. Conduct a systematic review of economic evaluations of breastfeeding support interventions. Co-create a NHS-tailored implementation and evaluation strategy framework to increase breastfeeding rates in the UK. Contribute to methodological development on involving stakeholders in systematic reviews. Design The study comprised two meta-analyses of breastfeeding support interventions, two mixed-methods evidence syntheses and two economic evaluations with embedded stakeholder engagement, including parents’ panels, stakeholder working groups, focus groups and workshops. Stakeholders interpreted and adapted the international evidence to ensure its relevance to UK settings and co-produced the toolkit. Review methods Review 1: update of Cochrane review ‘Support for healthy breastfeeding mothers with healthy term babies’ The Cochrane Pregnancy and Childbirth Group’s Trials Register was searched in May 2021. Healthy women and babies were those who did not require additional medical care. Interventions could be delivered as standalone breastfeeding support interventions (‘breastfeeding only’) or as part of a wider maternal and newborn health intervention (‘breastfeeding plus’) where additional services (e.g. vaccination, intrapartum care) are provided. Primary outcomes were stopping any or exclusive breastfeeding at 6 months and 4–6 weeks postpartum. We used standard Cochrane methods for data extraction, risk-of-bias assessment and statistical analysis. We used meta-regression to investigate statistical heterogeneity. Review 2: mixed-methods review of process evaluations linked to effective breastfeeding support interventions Six electronic databases were searched in March 2022. Eligible studies reported the views and experiences of delivering or receiving effective breastfeeding support interventions. Qualitative and quantitative findings were synthesised separately and then integrated into a theoretically informed cross-study synthesis. Review 3: economic evaluation review This review, with searches conducted in February 2021, considered value for money by appraising and synthesising the evidence of incremental costs and cost-effectiveness in comparison with a control. The eligibility criteria were the same as those of review 1, with the addition of relevant economic outcomes such as incremental cost-effectiveness ratios (ICERs). Quality assessment followed National Institute for Health and Care Excellence (NICE) guidance. Consistency between studies in evidence of cost-effectiveness was reviewed. Review 4: effectiveness of breastfeeding support for women with long-term conditions Searches were conducted in August 2022. Included studies involved women with a long-term physical or mental health condition. Primary outcomes were stopping any or exclusive breastfeeding at 4–8 weeks and 6 months. We used standard Cochrane methods for data extraction, risk-of-bias assessment and statistical analysis. Review 5: mixed-methods review of experiences of breastfeeding support for women with long-term conditions Searches were conducted in October 2022. Included studies reported primary research on the views and experiences of breastfeeding women with LTCs and/or support providers. Qualitative and quantitative findings were synthesised separately and then integrated into a theoretically informed cross-study synthesis. Review 6: review of economic evidence for breastfeeding support for women with long-term conditions The search strategy for review 3 was used for this review, with modification of the inclusion criteria for women with LTCs. Searches were conducted in August 2022. Quality assessment followed the NICE guidance. Stakeholder engagement Stakeholder engagement and toolkit development comprised online discussions, a modified Delphi study, face-to-face focus groups and four workshops. Participants were 23 stakeholders (health service providers and representatives of third-sector organisations), 16 parents in the parents’ panels and 15 women from a deprived and diverse locality in the focus group discussions. Results We found considerably more interventions designed for healthy women (review 1) than aimed at women with LTCs (review 2). ‘Breastfeeding only’ interventions probably have a small effect in reducing the number of healthy women stopping breastfeeding. However, ‘breastfeeding plus’ and interventions for women with LTCs probably have little or no effect on breastfeeding outcomes. In both reviews, approximately half of the studies were targeted at groups at higher risk of poor breastfeeding outcomes, and it is possible that the impact of support is different in these populations. Despite this, studies from review 2 found that women perceived the provision of support as positive, important and needed. Studies from review 5 echoed participants’ suggestions of potential strategies to improve breastfeeding support, the most widely reported being the need to involve wider sources of support (e.g. partners, family, friends, peers, external professionals, web-based resources) in supporting women with LTCs to breastfeed. In reviews 3 and 6, there was uncertainty in the cost-effectiveness of breastfeeding support interventions due to the limited number of studies and lack of good-quality evidence. More specific findings from each review are presented below. Review 1 This updated review includes 125 interventions reported in 116 trials with more than 98,816 mother–infant pairs. Ninety-one interventions were ‘breastfeeding only’ and 34 were ‘breastfeeding plus’. The overall risk of bias of trials included in the review was mixed. Blinding of participants and personnel is not feasible in such interventions, and, as studies used self‐report breastfeeding data, there is also a risk of bias in outcome assessment. Moderate‐certainty evidence indicated that ‘breastfeeding only’ support probably reduced the number of women stopping breastfeeding for all primary outcomes: stopping any breastfeeding at 6 months [relative risk (RR) 0.93, 95% confidence interval (CI) 0.89 to 0.97]; stopping exclusive breastfeeding at 6 months (RR 0.90, 95% CI 0.88 to 0.93); stopping any breastfeeding at 4–6 weeks (RR 0.88, 95% CI 0.79 to 0.97); and stopping exclusive breastfeeding at 4–6 weeks (RR 0.83, 95% CI 0.76 to 0.90). The evidence for ‘breastfeeding plus’ was less consistent. Interventions may have a beneficial effect on reducing the number of women stopping exclusive breastfeeding at 4–6 weeks (RR 0.73, 95% CI 0.57 to 0.95, very uncertain evidence) and 6 months (RR 0.79, 95% CI 0.70 to 0.90, moderate-certainty evidence). However, ‘breastfeeding plus’ support probably results in little to no difference in other breastfeeding outcomes. We conducted meta‐regression to explore substantial heterogeneity for the primary outcomes. Minimal differential effects were found except for a schedule of four to eight visits possibly associated with more beneficial effects. There was a lack of evidence for UK effective interventions. Review 2 We included 16 studies linked to 10 effective interventions. The quality of the included studies was mixed, but all studies’ findings were judged to be at least fairly well supported by data. The synthesis identified 18 factors affecting implementation of interventions and data-driven analytical themes. Mapping to the Consolidated Framework for Implementation Research resulted in three overarching themes: (1) assessing the needs of those delivering and receiving breastfeeding support interventions, (2) assessing the context and optimising delivery and engagement with breastfeeding support interventions and (3) reflecting and evaluating the success of implementing and providing breastfeeding support. Included studies identified implementation challenges relating to the needs, preferences and priorities of intervention providers and recipients. Overall, breastfeeding women perceived support as positive, important and needed. Breastfeeding supporter training enabled implementation teams to address breastfeeding supporters’ needs. Studies reported contextual factors (e.g. alignment with local policies) affecting the implementation and delivery of breastfeeding support interventions as well as tailoring strategies (e.g. community involvement, use of lay language, responsive support content/information) to address contextual factors. Reports about implementation success focused on key implementation outcomes such as satisfaction, fidelity or usefulness. Review 3 We included 39 economic evaluations, nine of which were deemed directly or partially applicable to the UK system. For ‘breastfeeding only’ support, evidence from one study suggested that the intervention was unlikely to be cost-effective [£56,074.98 per quality-adjusted life-year gained at 2022 Great British pounds (GBP) prices]. There was evidence for the incremental cost per additional woman breastfeeding (any or exclusive), with ICERs ranging from £67 to £112 from 2 weeks up to 8 weeks postpartum, and from £2446 to £4226 up to 6 months postpartum. Without willingness-to-pay thresholds, value for money is unclear. Evidence for ‘breastfeeding plus’ support suggests that this is not cost-effective; however, there was a lack of good-quality evaluations, with inconsistency in results. Where evidence of sensitivity analysis was reported for handling uncertainty, ICERs were upheld. Scenario analyses from the base case did show changes in costing the intervention, which suggested that costs were sensitive. Eight studies were deemed to have potentially very serious limitations due to short time horizons and a lack of extrapolation beyond within-trial data. These limitations affect conclusions about cost-effectiveness. Review 4 Twenty-two studies of 23 interventions were included. The meta-analyses included 5048 mother–infant pairs. The most common condition, in nine studies, was overweight and obesity. A further three studies were of women with gestational diabetes mellitus. Five studies included women with human immunodeficiency virus (HIV). Two studies were of women with substance misuse problems, and one was of women with anxiety and depression. Interventions varied in whether they provided breastfeeding support only or if they also provided support for the LTC. The overall risk of bias of trials was generally high. Blinding of participants and personnel is not feasible in such interventions. About half of the studies were rated as being at high or unclear risk of allocation concealment and incomplete outcome data. All studies were rated as being at high or unclear risk of selective outcome reporting. There was little to no difference between intervention and control for any of the primary outcomes. We judged these outcomes to be of low and moderate certainty. Review 5 We included 24 studies. The health conditions covered were HIV, obesity and overweight, substance use, diabetes in pregnancy, disabilities and a rare genetic disorder. The overall quality of included studies was mixed. Four key themes were identified: (1) additional breastfeeding support needs for women with LTCs; (2) variable or insufficient availability of breastfeeding support for mothers with LTCs; (3) experiences of breastfeeding support of mothers with LTCs suggesting complex breastfeeding journeys; and (4) suggestions from participants of potential strategies to improve breastfeeding support. Review 6 We included five economic evaluations. The conditions assessed were HIV, obesity, prenatal opioid use and medically high risk (maternal hypertension and diabetes prior to birth). Each intervention assessed in full economic evaluations was deemed cost-effective for the base case. However, each study failed to meet one or more applicability criteria, which is likely to change the conclusions about cost-effectiveness. Embedded stakeholder engagement and patient and public involvement Two stakeholder working groups with 23 members and two parents’ panels with 16 members met virtually several times throughout. The main study stakeholder group and parents’ panel discussed the realities of breastfeeding, ranked intervention transferability criteria, highlighted barriers to accessing and providing breastfeeding support and prioritised implementation strategies to overcome barriers. Six focus group discussions involving 23 participants from an area of high socioeconomic disadvantage represented the perspectives of communities who are less likely to breastfeed. The other stakeholder working group and parents’ panel provided first-hand accounts of breastfeeding, and of providing breastfeeding support for women with multimorbidities. They discussed adapting interventions identified in the main study to meet the needs of women with LTCs. The views and suggestions of all stakeholders and parents guided all stages of the project and directly influenced the co-production workshops. Four workshops across the UK were attended by 87 participants representing parents and third-sector organisations, healthcare practitioners, service managers and commissioners, policy-makers and academics. The workshop output was a toolkit for implementing breastfeeding support interventions in the UK. The toolkit comprises evidence-based recommendations for breastfeeding support services, prioritised criteria for adapting the evidence-based recommendations to local services, and guidance on implementing new breastfeeding support services, planning the implementation strategy and evaluating the breastfeeding support services. A discrete choice experiment showed that participants valued additional breastfeeding support and were willing to pay £89.91 per woman to achieve a 1% reduction in the number of women stopping any breastfeeding at 6 weeks, and £105.04 for a 1% reduction in stopping exclusive breastfeeding. Conclusions ‘Breastfeeding only’ support can increase the duration and exclusivity of breastfeeding in healthy women. For ‘breastfeeding plus’ and interventions for women with LTCs the evidence is less certain and there is probably little effect on breastfeeding outcomes. As the mixed-methods synthesis and stakeholder work identified that women with LTCs face additional challenges when breastfeeding, more research is needed to develop effective and cost-effective support. Evidence for the effectiveness and cost-effectiveness of breastfeeding support interventions in the UK is lacking. Implications for health care Decision-makers and frontline practitioners can use the toolkit to inform implementation efforts, to overcome barriers specific to their settings and to tailor evidence-based interventions to their populations. Key to success will be addressing health system barriers and enhancing the skills, knowledge and confidence of practitioners. Regarding women with LTCs, stakeholder engagement suggested health services could integrate infant-feeding specialists with the multidisciplinary team to give infant feeding a higher profile in obstetric and medical care. Recommendations for research (numbered in priority order) Development and evaluation of breastfeeding support interventions for women with LTCs and multimorbidities, particularly mental health conditions, overweight/obesity and gestational diabetes. Focus on understanding the components of breastfeeding support interventions that make them effective, including which components would be more effective in populations at risk of poorer breastfeeding outcomes (e.g. areas of high socioeconomic deprivation), and understanding why ‘breastfeeding plus’ interventions are less effective. Implementing and evaluating effective breastfeeding support in the UK for all women. This could evaluate the prototype intervention proposed in this report tailored to local contexts via implementation and effectiveness and cost-effectiveness studies or using quality improvement methodology. Study registration This study is registered as PROSPERO CRD42022337239, CRD42021229769 and CRD42022374509. The reviews of economic evidence were not registered; however, the review protocol can be accessed via the repository held by Queen’s University Belfast Research Portal (https://pure.qub.ac.uk/). Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR130995) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 20. See the NIHR Funding and Awards website for further award information.

IntroductionHistorically, secular and seasonal trend analyses have been examined using self-report measures of intake. Rarely are objective measures and known determinants of dietary intake used in these analyses. Our objective was to quantify the seasonal and secular differences in an objective ad libitum intake paradigm while considering the contribution of determinants, such as fat-free mass (FFM) index and spontaneous physical activity (SPA) limited to the restricted space of a whole-room calorimeter.MethodsFor this study, recruitment of N = 292 healthy, diabetes free, adults occurred from 1999 to 2020. Assessment during their 10-day stay included body composition (by DXA), SPA (by an approximately 24-h stay in whole-room calorimetry), and ad libitum intake (by a vending machine for 3 days). This secondary analysis used general linear models (GLM) to investigate secular and seasonal differences while adjusting for sex, age, FFM index, FM (fat mass) index, SPA, and race/ethnicity.ResultsFFM index and SPA were positively associated with all intake measures (p < 0.05). In all adjusted seasonal models, season did not affect intake. Adjusted secular trends models (kcals/year) demonstrated a decrease in total kcals (β = −55), intake as percent weight maintaining energy needs (β = −2), protein kcals (β = −10), fat kcals (β = −27), and carbohydrates kcals (β = −22) (all p < 0.05). After further adjustment for SPA, significance remained in all intake measures (p < 0.05). Secular trends in body composition revealed no changes in weight, BMI, and percent body fat (all p > 0.20).DiscussionOur results indicate that over time, ad libitum intake decreased in this controlled research setting and remained significant even after accounting for positive determinants of intake. A significant ad libitum decrease, coupled with no change in body composition, may highlight a participant bias toward calorie restriction in a controlled setting over time and deserves further investigation.

Social care practitioners are often under-represented in research activity and output. Evidence-based practice enables social care practitioners to develop/engage the skills to evaluate evidence and be more actively involved in research. REalist Synthesis Of non-pharmacologicaL interVEntions for antipsychotic-induced weight gain (RESOLVE) is a NIHR-funded study where realist synthesis is used to understand and explain how, why, for whom, and in what contexts non-pharmacological interventions help service users, with severe mental illness, to manage antipsychotic-induced weight gain. Social care practitioners are a key part of the team providing care for people living with severe mental illness and therefore supporting antipsychotic-induced weight gain. The current study, RESOLVE 2, uses realist evaluation and RESOLVE as an illustrative example to help understand why and how social care practitioners engage (or not) with research. Semi-structured, audio-recorded interviews will be undertaken with a purposive sample of approximately 20 social care practitioners working with people who have severe mental illness, are treated with antipsychotics, and have experienced weight gain. Participants will be recruited from NHS Trusts and recruitment avenues such as social media and personal networks. Topics discussed during interviews will include barriers and facilitators to engagement in research, current, and past engagement as well as recommendations for researchers and other practitioners. Interview recordings will be transcribed verbatim and analyzed using realist evaluation which will allow in-depth causal explanations for research engagement. Better understanding of research engagement by social care practitioners will allow for evidence-based practice and better patient outcomes within these settings.

Background Parkinson’s is a common progressive neurological condition characterized by motor and non-motor deficits. Physical activity and exercise can improve health, but many people with Parkinson’s (PwP) have trouble reaching the recommended dosage. Our recent literature review found improvements in exercise adherence with behavioural change interventions, but it remains unclear which are most effective. Further qualitative research and patient and public involvement has informed a novel behavioural change intervention to be tested alongside an existing exercise program. Objective To examine the feasibility of behavioural change techniques delivered alongside an exercise programme to improve physical activity, function, and self-efficacy in PwP (and study procedures) to inform a future pilot RCT trial. Methods A parallel-arm single blinded randomised feasibility study. Twenty participants with Parkinson’s (Hoehn and Yahr stage 1-3) will be recruited from a physiotherapy primary-care waiting list. Following written consent, and baseline assessment, the participants will be randomly allocated to the intervention (n=10) or the control group (n=10). Both groups will receive usual care, which includes a weekly program of a multidisciplinary education, a supervised exercise class and a prescribed home exercise program. The intervention group will receive additional behavioural change techniques, targeting behaviour regulation, belief about capabilities and social influences. Class and home exercise adherence, behavioural component uptake and adherence, and negative events will be recorded. Outcomes will include enrolment and maintenance rates, physical function, falls, physical activity, and exercise self-efficacy measured pre- and post- the 12-week program (in-person). Surveys will be used to compare experiences and satisfaction between groups. Exit interviews will be completed with the intervention group only, exploring their experience of the behavioural change techniques. Discussion The results will help inform a future pilot RCT, based on the intervention acceptability, consent rate, maintenance, and protocol integrity. Trial Registration ClincialTrials.gov NCT06192628