Fetal Diagnosis of Supravalvular Aortic Stenosis and Pulmonary Stenosis in a Family with Non-Syndromic Elastin Mutation.

Supravalvular aortic stenosis (SVAS) has been well described in Williams-Beuren Syndrome and non-syndromic elastin (ELN) mutations. Non-syndromic ELN mutations are inherited in an autosomal dominant pattern with incomplete penetrance and variable expressivity. ELN haploinsufficiency leads to progressive arteriopathy, typically affecting the aortic sinotubular junction. Multi-level pulmonary stenosis has also been reported and biventricular obstruction may portend a worse prognosis. Fetal presentation of ELN mutation with SVAS has not been previously reported in the literature. We present a case of fetal diagnosis of SVAS and multi-level pulmonary stenosis in a family with a known pathogenic ELN mutation (Exon 6, c.278del [p.Pro93Leufs*29]). On the fetus' initial fetal echo, there was only mild flow acceleration through the aortic outflow tract, however, she went on to develop progressive bilateral obstruction. In the early post-natal period, the child was clinically asymptomatic and showed similar mild SVAS and mild valvar and supravalvular pulmonary stenosis. Our case highlights the need for serial monitoring of fetuses with suspected or confirmed ELN arteriopathy.

Loss of Neuron Navigator 2 Impairs Brain and Cerebellar Development.

Cerebellar hypoplasia and dysplasia encompass a group of clinically and genetically heterogeneous disorders frequently associated with neurodevelopmental impairment. The Neuron Navigator 2 (NAV2) gene (MIM: 607,026) encodes a member of the Neuron Navigator protein family, widely expressed within the central nervous system (CNS), and particularly abundant in the developing cerebellum. Evidence across different species supports a pivotal function of NAV2 in cytoskeletal dynamics and neurite outgrowth. Specifically, deficiency of Nav2 in mice leads to cerebellar hypoplasia with abnormal foliation due to impaired axonal outgrowth. However, little is known about the involvement of the NAV2 gene in human disease phenotypes. In this study, we identified a female affected with neurodevelopmental impairment and a complex brain and cardiac malformations in which clinical exome sequencing led to the identification of NAV2 biallelic truncating variants. Through protein expression analysis and cell migration assay in patient-derived fibroblasts, we provide evidence linking NAV2 deficiency to cellular migration deficits. In model organisms, the overall CNS histopathology of the Nav2 hypomorphic mouse revealed developmental anomalies including cerebellar hypoplasia and dysplasia, corpus callosum hypo-dysgenesis, and agenesis of the olfactory bulbs. Lastly, we show that the NAV2 ortholog in Drosophila, sickie (sick) is widely expressed in the fly brain, and sick mutants are mostly lethal with surviving escapers showing neurobehavioral phenotypes. In summary, our results unveil a novel human neurodevelopmental disorder due to genetic loss of NAV2, highlighting a critical conserved role of the NAV2 gene in brain and cerebellar development across species.

Variability in skilled nursing facility screening and admission processes: Implications for value-based purchasing.

BACKGROUND: Hospitalized older adults are increasingly admitted to skilled nursing facilities (SNFs) for posthospital care. However, little is known about how SNFs screen and evaluate potential new admissions. In an era of increasing emphasis on postacute care outcomes, these processes may represent an important target for interventions to improve the value of SNF care. PURPOSE: The aim of this study was to understand (a) how SNF clinicians evaluate hospitalized older adults and make decisions to admit patients to an SNF and (b) the limitations and benefits of current practices in the context of value-based payment reforms. METHODS: We used semistructured interviews to understand the perspective of 18 clinicians at three unique SNFs-including physicians, nurses, therapists, and liaisons. All transcripts were analyzed using a general inductive theme-based approach. RESULTS: We found that the screening and admission processes varied by SNF and that variability was influenced by three key external pressures: (a) inconsistent and inadequate transfer of medical documentation, (b) lack of understanding among hospital staff of SNF processes and capabilities, and (c) hospital payment models that encouraged hospitals to discharge patients rapidly. Responses to these pressures varied across SNFs. For example, screening and evaluation processes to respond to these pressures included gaining access to electronic medical records, providing inpatient physician consultations prior to SNF acceptance, and turning away more complex patients for those perceived to be more straightforward rehabilitation patients. CONCLUSIONS: We found facility behavior was driven by internal and external factors with implications for equitable access to care in the era of value-based purchasing. PRACTICE IMPLICATIONS: SNFs can most effectively respond to these pressures by increasing their agency within hospital-SNF relationships and prioritizing more careful patient screening to match patient needs and facility capabilities.

Operationalizing an Implementation Framework to Disseminate a Care Coordination Program for Rural Veterans.

OBJECTIVE: Understanding how to successfully implement care coordination programs across diverse settings is critical for disseminating best practices. We describe how we operationalized the Practical Robust Implementation and Sustainability Model (PRISM) to guide the assessment of local context prior to implementation of the rural Transitions Nurse Program (TNP) at five facilities across the Veterans Health Administration (VHA). METHODS: We operationalized PRISM to create qualitative data collection techniques (interview guides, semi-structured observations, and a group brainwriting premortem) to assess local context, the current state of care coordination, and perceptions of TNP prior to implementation at five facilities. We analyzed data using deductive-inductive framework analysis to identify themes related to PRISM. We adapted implementation strategies at each site using these findings. RESULTS: We identified actionable themes within PRISM domains to address during implementation. The most commonly occurring PRISM domains were "organizational characteristics" and "implementation and sustainability infrastructure." Themes included a disconnect between primary care and hospital inpatient teams, concerns about work duplication, and concerns that one nurse could not meet the demand for the program. These themes informed TNP implementation. CONCLUSIONS: The use of PRISM for pre-implementation site assessments yielded important findings that guided adaptations to our implementation approach. Further, barriers and facilitators to TNP implementation may be common to other care coordination interventions. Generating a common language of barriers and facilitators in care coordination initiatives will enhance generalizability and establish best practices. IMPACT STATEMENTS: TNP is a national intensive care coordination program targeting rural Veterans. We operationalized PRISM to guide implementation efforts. We effectively elucidated facilitators, barriers, and unique contextual factors at diverse VHA facilities. The use of PRISM enhances the generalizability of findings across care settings and may optimize implementation of care coordination interventions in the VHA.

Chronic Maternal Hyperoxygenation and Effect on Cerebral and Placental Vasoregulation and Neurodevelopment in Fetuses with Left Heart Hypoplasia.

INTRODUCTION: In a pilot study of chronic maternal hyperoxygenation (CMH) in left heart hypoplasia (LHH), we sought to determine effect estimates of CMH on head size, vascular resistance indices, and neurodevelopment compared to controls. MATERIAL AND METHODS: Nine gravidae meeting the inclusion criteria (fetal LHH, ≥25.9 weeks' gestation, and ≥10% increase in percent aortic flow after acute hyperoxygenation) were prospectively enrolled. Controls were 9 contemporary gravidae with fetal LHH without CMH. Brain growth and Doppler-derived estimates of fetal cerebrovascular and placental resistance were blindly evaluated and compared using longitudinal regression. Postnatal anthropomorphic and neurodevelopmental assessments were compared. RESULTS: There was no difference in baseline fetal measures between groups. There was significantly slower biparietal diameter (BPD) growth in the CMH group (z-score change -0.03 ± 0.02 vs. +0.09 ± 0.05 units/week, p = 0.02). At 6 months postnatal age, the mean head circumference z-score in the CMH group was smaller than that of controls (-0.20 ± 0.58 vs. +0.85 ± 1.11, p = 0.048). There were no differences in neurodevelopmental testing at 6 and 12 months. DISCUSSION: In this pilot study, relatively diminished fetal BPD growth and smaller infant head circumference z-scores at 6 months were noted with in utero CMH exposure.

Brainwriting Premortem: A Novel Focus Group Method to Engage Stakeholders and Identify Preimplementation Barriers.

BACKGROUND: Many health care interventions encounter implementation challenges because of inadequate stakeholder engagement and identification of barriers. The brainwriting premortem technique is the silent sharing of written ideas about why an intervention failed. The method can engage stakeholders and identify barriers more efficiently than traditional brainstorming focus groups. PURPOSE: We evaluated the method during a transition of care intervention in the Veterans Health Administration (VA). Clinicians from 10 VA facilities participated in 10 brainwriting premortem sessions. METHODS: Using descriptive and content analytic methods, we assessed the quantity and quality of ideas generated, facilitator experience, and participant psychological safety. RESULTS: In total, 217 unique ideas were generated. Many were deemed high quality. The written data were immediately available for analysis, allowing rapid feedback and real-time decision making. Participants reported high satisfaction and psychological safety. CONCLUSION: The brainwriting premortem approach is a novel, efficient alternative to brainstorming focus groups that can rapidly inform program implementation at minimal cost.

A genome-wide association study of congenital cardiovascular left-sided lesions shows association with a locus on chromosome 20.

Congenital heart defects involving left-sided lesions (LSLs) are relatively common birth defects with substantial morbidity and mortality. Previous studies have suggested a high heritability with a complex genetic architecture, such that only a few LSL loci have been identified. We performed a genome-wide case-control association study to address the role of common variants using a discovery cohort of 778 cases and 2756 controls. We identified a genome-wide significant association mapping to a 200 kb region on chromosome 20q11 [P= 1.72 × 10-8 for rs3746446; imputed Single Nucleotide Polymorphism (SNP) rs6088703 P= 3.01 × 10-9, odds ratio (OR)= 1.6 for both]. This result was supported by transmission disequilibrium analyses using a subset of 541 case families (lowest P in region= 4.51 × 10-5, OR= 1.5). Replication in a cohort of 367 LSL cases and 5159 controls showed nominal association (P= 0.03 for rs3746446) resulting in P= 9.49 × 10-9 for rs3746446 upon meta-analysis of the combined cohorts. In addition, a group of seven SNPs on chromosome 1q21.3 met threshold for suggestive association (lowest P= 9.35 × 10-7 for rs12045807). Both regions include genes involved in cardiac development-MYH7B/miR499A on chromosome 20 and CTSK, CTSS and ARNT on chromosome 1. Genome-wide heritability analysis using case-control genotyped SNPs suggested that the mean heritability of LSLs attributable to common variants is moderately high ([Formula: see text] range= 0.26-0.34) and consistent with previous assertions. These results provide evidence for the role of common variation in LSLs, proffer new genes as potential biological candidates, and give further insight to the complex genetic architecture of congenital heart disease.

Evaluating the Quality of Patient Decision-Making Regarding Post-Acute Care.

BACKGROUND: Despite a national focus on post-acute care brought about by recent payment reforms, relatively little is known about how hospitalized older adults and their caregivers decide whether to go to a skilled nursing facility (SNF) after hospitalization. OBJECTIVE: We sought to understand to what extent hospitalized older adults and their caregivers are empowered to make a high-quality decision about utilizing an SNF for post-acute care and what contextual or process elements led to satisfaction with the outcome of their decision once in SNF. DESIGN: Qualitative inquiry using the Ottawa Decision Support Framework (ODSF), a conceptual framework that describes key components of high-quality decision-making. PARTICIPANTS: Thirty-two previously community-dwelling older adults (≥ 65 years old) and 22 caregivers interviewed at three different hospitals and three skilled nursing facilities. MAIN MEASURES: We used key components of the ODSF to identify elements of context and process that affected decision-making and to what extent the outcome was characteristic of a high-quality decision: informed, values based, and not associated with regret or blame. KEY RESULTS: The most important contextual themes were the presence of active medical conditions in the hospital that made decision-making difficult, prior experiences with hospital readmission or SNF, relative level of caregiver support, and pressure to make a decision quickly for which participants felt unprepared. Patients described playing a passive role in the decision-making process and largely relying on recommendations from the medical team. Patients commonly expressed resignation and a perceived lack of choice or autonomy, leading to dissatisfaction with the outcome. CONCLUSIONS: Understanding and intervening to improve the quality of decision-making regarding post-acute care supports is essential for improving outcomes of hospitalized older adults. Our results suggest that simply providing information is not sufficient; rather, incorporating key contextual factors and improving the decision-making process for both patients and clinicians are also essential.

Adaptation of Lean Six Sigma Methodologies for the Evaluation of Veterans Choice Program at 3 Urban Veterans Affairs Medical Centers.

OBJECTIVE: The Veterans Health Administration (VHA) is adapting to meet the changing needs of our Veterans. VHA leaders are promoting quality improvement strategies including Lean Six Sigma (LSS). This study used LSS tools to evaluate the Veterans Choice Program (VCP), a program that aims to improve access to health care services for eligible Veterans by expanding health care options to non-VHA providers. RESEARCH DESIGN: LSS was utilized to assess the current process and efficiency patterns of the VCP at 3 VHA Medical Centers. LSS techniques were used to assess data obtained through semistructured interviews with Veterans, staff, and providers to describe and evaluate the VCP process by identifying wastes and defects. RESULTS: The LSS methodology facilitated the process of targeting priorities for improvement and constructing suggestions to close identified gaps and inefficiencies. Identified key process wastes included inefficient exchange of clinical information between stakeholders in and outside of the VHA; poor dissemination of VCP programmatic information; shortages of VCP-participating providers; duplication of appointments; declines in care coordination; and lack of program adaptability to local processes. Recommendations for improvement were formulated using LSS. CONCLUSIONS: This evaluation illustrates how LSS can be utilized to assess a nationally mandated health care program. By focusing on stakeholder, staff, and Veteran perspectives, process defects in the VCP were identified and improvement recommendations were made. However, the current LSS language used is not intuitive in health care and similar applications of LSS may consider using new language and goals adapted specifically for health care.

Study protocol: improving the transition of care from a non-network hospital back to the patient's medical home.

BACKGROUND: The process of transitioning Veterans to primary care following a non-Veterans Affairs (VA) hospitalization can be challenging. Poor transitions result in medical complications and increased hospital readmissions. The goal of this transition of care quality improvement (QI) project is to identify gaps in the current transition process and implement an intervention that bridges the gap and improves the current transition of care process within the Eastern Colorado Health Care System (ECHCS). METHODS: We will employ qualitative methods to understand the current transition of care process back to VA primary care for Veterans who received care in a non-VA hospital in ECHCS. We will conduct in-depth semi-structured interviews with Veterans hospitalized in 2015 in non-VA hospitals as well as both VA and non-VA providers, staff, and administrators involved in the current care transition process. Participants will be recruited using convenience and snowball sampling. Qualitative data analysis will be guided by conventional content analysis and Lean Six Sigma process improvement tools. We will use VA claim data to identify the top ten non-VA hospitals serving rural and urban Veterans by volume and Veterans that received inpatient services at non-VA hospitals. Informed by both qualitative and quantitative data, we will then develop a transitions care coordinator led intervention to improve the transitions process. We will test the transition of care coordinator intervention using repeated improvement cycles incorporating salient factors in value stream mapping that are important for an efficient and effective transition process. Furthermore, we will complete a value stream map of the transition process at two other VA Medical Centers and test whether an implementation strategy of audit and feedback (the value stream map of the current transition process with the Transition of Care Dashboard) versus audit and feedback with Transition Nurse facilitation of the process using the Resource Guide and Transition of Care Dashboard improves the transition process, continuity of care, patient satisfaction and clinical outcomes. DISCUSSION: Our current transition of care process has shortcomings. An intervention utilizing a transition care coordinator has the potential to improve this process. Transitioning Veterans to primary care following a non-VA hospitalization is a crucial step for improving care coordination for Veterans.

Nurses' Role in Managing "The Fit" of Older Adults in Skilled Nursing Facilities.

Post-acute care for older adults often involves transfer to a skilled nursing facility (SNF) following hospital discharge. This transition is often poorly coordinated and leaves older adults at risk for poor health outcomes, but new payment models offer opportunities to align improved care practices with payments. There is a dearth of evidence regarding the role of nursing and its potential to improve hospital to SNF care transitions. Ninety-nine semi-structured interviews were conducted with clinicians, patients, and caregivers from three hospitals and three SNFs. Results indicate a sharp contrast in the roles of hospital nurses-who are often silent partners in post-acute care decision making-and SNF nurses, who take a primary role as managing "the fit" for patients transitioning to a SNF. Nurses are uniquely positioned to make needed changes to culture to adapt to new payment models and improve patient outcomes. [Journal of Gerontological Nursing, 43(12), 11-20.].

Long term functional outcomes after early childhood pollicization.

STUDY DESIGN: Retrospective Cohort INTRODUCTION: Important outcomes of polliciation to treat thumb hypoplasia/aplasia include strength, function, dexterity, and quality of life. PURPOSE OF THE STUDY: To evaluate outcomes and examine predictors of outcome after early childhood pollicization. METHODS: 8 children (10 hands) were evaluated 3-15 years after surgery. Physical examination, questionnaires, grip and pinch strength, Box and Blocks, 9-hole pegboard, and strength-dexterity (S-D) tests were performed. RESULTS: Pollicized hands had poor strength and performance on functional tests. Six of 10 pollicized hands had normal dexterity scores but less stability in maintaining a steady-state force. Predictors of poorer outcomes included older age at surgery, reduced metacarpophalangeal and interphalangeal range of motion, and radial absence. DISCUSSION: Pollicization resulted in poor strength and overall function, but normal dexterity was often achieved using altered control strategies. CONCLUSIONS: Most children should obtain adequate dexterity despite weakness after pollicization except older or severely involved children. LEVEL OF EVIDENCE: IV.

Using community-based, participatory qualitative research to identify determinants of routine vaccination drop-out for children under 2 in Lilongwe and Mzimba North Districts, Malawi.

OBJECTIVE: In recent years, full childhood routine immunisation coverage has fallen by 5% to levels not seen since 2008; between 2019 and 2021, 67 million children were undervaccinated. We aimed to identify and describe the determinants of vaccination drop-out from the perspectives of caregivers and health workers in Malawi. DESIGN: We used a community-based participatory research approach to collect data through photo elicitation, short message service exchanges, in-depth interviews and observations. We used a team-based approach for thematic analysis, guided by the Behavioural and Social Drivers of Vaccination framework. SETTING: The study was conducted in Lilongwe and Mzimba North Districts in Malawi, representing urban and rural settings, respectively. PARTICIPANTS: Participants included caregivers of partially vaccinated (n=38) and fully vaccinated (n=12) children between 25 and 34 months and Community Health Workers (n=20) who deliver vaccines. Caregiver participants were identified through health facility vaccination registers and with the assistance of community health volunteers. RESULTS: We identified five principal drivers of routine vaccination drop-out: (1) poor caregiver knowledge of the vaccine schedule and how many vaccines are needed for full vaccination; (2) caregivers' fear of repercussions after not following vaccination guidelines; (3) rumours and concerns if vaccines are repeated or new ones are introduced; (4) high opportunity cost of health facility visits, exacerbated by wait times, stockouts and missed opportunities and (5) limited family support and vaccination burden placed largely on mothers. Key differences between rural and urban settings related to practices around health cards and vaccine wastage, wait times, migrant and tenant communities, and social support systems. CONCLUSIONS: Immunisation interventions should be tailored to address drivers of drop-out in the community, the health facility and beyond. Service quality, timeliness and reliability need to be improved, and tailored messaging and education are needed, especially in response to COVID-19-related misinformation and introductions of new, routine vaccines.

In Utero Presentation of Left Ventricular Aneurysm.

Congenital left ventricular aneurysm, pseudoaneurysm, and diverticulum are rare entities. These diagnoses can be made pre- and/or postnatally. Although these entities overlap clinically and morphologically, important distinctions can allow for accurate diagnoses. Appropriate diagnosis can be imperative for risk stratification and guidance of prenatal and postnatal management. The case described in the present report highlights a challenging case of a fetal left ventricular aneurysm, management during the prenatal and postnatal periods, and important differentiating features from a ventricular diverticulum and pseudoaneurysm.

Preclerkship Medical Students' Use of Third-Party Learning Resources.

Importance: Undergraduate medical education increasingly relies on asynchronous, virtual learning; and medical educators have observed students engaging in self-directed learning outside of their institutional curriculum using widely available third-party resources. If medical educators better understand how students are learning, they may uncover novel opportunities to improve preclerkship education. Objective: To explore how and why preclerkship medical students use third-party learning resources. Design, Setting, and Participants: This qualitative study recruited second-year medical students from 7 public and private allopathic US medical schools and conducted 7 virtual focus groups (1 per institution) from September 2022 to January 2023, exploring how and why students use third-party resources. Data were iteratively analyzed in parallel with focus groups using constructivist grounded theory methodology. Data analysis was performed from October 2022 to February 2023. Results: Fifty-eight second-year US medical students who had used a third-party resource at least once participated; 36 (61%) identified as women; 13 (23%) identified as Asian, 6 (11%) as Black, 30 (53%) as White, 6 (11%) as multiracial, and 4 (7%) as other; 6 (10%) identified as Hispanic, Latino, or Spanish origin, and 52 (90%) identified as non-Hispanic, Latino, or Spanish origin; 48 (83%) were aged 23 to 25 years. Participants described engaging in a cyclical process of deciding whether and how to use third-party resources. Four broad themes were identified: (1) hearing about resources, (2) selecting resources, (3) using resources, and (4) tensions and possible solutions. Participants largely heard about third-party resources from peers and turned to resources out of dissatisfaction with some aspect of their medical school curriculum. Students used resources in various ways that were user-dependent and context-dependent. Participants endorsed multiple benefits over their in-house curricula, particularly efficiency, clarity, and concision. Tensions included navigating resource drawbacks and the perception of an antagonistic relationship between medical schools and third-party resources. Participants suggested that medical schools examine the resources, recommend specific ones, integrate them into the curriculum, and subsidize their cost. Conclusions and Relevance: In this qualitative study of preclerkship medical student use of third-party resources, participants perceived that the resources had numerous benefits for learning and suggested that medical schools should more formally acknowledge and integrate their use.

Topical and systemic GLP-1R agonist administration both rescue retinal ganglion cells in hypertensive glaucoma.

Glaucomatous neurodegeneration, a blinding disease affecting millions worldwide, has a need for the exploration of new and effective therapies. Previously, the glucagon-like peptide-1 receptor (GLP-1R) agonist NLY01 was shown to reduce microglia/macrophage activation, rescuing retinal ganglion cells after IOP elevation in an animal model of glaucoma. GLP-1R agonist use is also associated with a reduced risk for glaucoma in patients with diabetes. In this study, we demonstrate that several commercially available GLP-1R agonists, administered either systemically or topically, hold protective potential in a mouse model of hypertensive glaucoma. Further, the resulting neuroprotection likely occurs through the same pathways previously shown for NLY01. This work contributes to a growing body of evidence suggesting that GLP-1R agonists represent a viable therapeutic option for glaucoma.

Functional characterization of age-dependent p16 epimutation reveals biological drivers and therapeutic targets for colorectal cancer.

BACKGROUND: Methylation of the p16 promoter resulting in epigenetic gene silencing-known as p16 epimutation-is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-related p16 epimutation in intestinal tumorigenesis. METHODS: We established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs: Apc mutation and p16 epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA sequencing (RNA-seq), quantitative PCR, and flow cytometry. We performed single-cell RNA sequencing (scRNA-seq) to characterize tumor-infiltrating immune cells throughout tumor progression. We tested whether anti-PD-L1 immunotherapy affects overall survival of tumor-bearing mice and whether inhibition of both epigenetic regulation and immune checkpoint is more efficacious. RESULTS: Mice carrying combined Apc mutation and p16 epimutation had significantly shortened survival and increased tumor growth compared to those with Apc mutation only. Intriguingly, colon tumors with p16 epimutation exhibited an activated interferon pathway, increased expression of programmed death-ligand 1 (Pdl1), and enhanced infiltration of immune cells. scRNA-seq further revealed the presence of Foxp3+ Tregs and γδT17 cells, which contribute to an immunosuppressive tumor microenvironment (TME). Furthermore, we showed that a combined therapy using an inhibitor of DNA methylation and a PD-L1 immune checkpoint inhibitor is more effective for improving survival in tumor-bearing mice than blockade of either pathway alone. CONCLUSIONS: Our study demonstrated that age-dependent p16 epimutation creates a permissive microenvironment for malignant transformation of polyps to colon cancer. Our findings provide a mechanistic rationale for future targeted therapy in patients with p16 epimutation.

Determinants of immunisation dropout among children under the age of 2 in Zambézia province, Mozambique: a community-based participatory research study using Photovoice.

OBJECTIVE: Immunisations are highly impactful, cost-effective public health interventions. However, substantial gaps in complete vaccination coverage persist. We aimed to describe caregivers' immunisation experiences and identify determinants of vaccine dropout. DESIGN: We used a community-based participatory research approach employing Photovoice, SMS (short messaging service) exchanges and in-depth interviews. A team-based approach was used for thematic analysis. The Increasing Vaccination Model guided the analysis and identification of vaccination facilitators and barriers. SETTING: This study was conducted in Zambézia province, Mozambique, in Namarroi and Gilé districts, where roughly 19% of children under 2 start but do not complete the recommended vaccination schedule. PARTICIPANTS: Participants were identified through health facility vaccination records and included caregivers of children aged 25-34 months who were fully vaccinated (n=10) and partially vaccinated (n=22). We also collected data from 12 health workers responsible for delivering immunisations at the selected health facilities. RESULTS: Four main patterns of barriers leading to dropout emerged: (1) social norms and limited family support place the immunisation burden on mothers; (2) perceived poor quality of health services reduces caregivers' trust in vaccination services; (3) concern about side effects causes vaccine hesitancy; and (4) caregivers hesitate to seek and advocate for vaccination due to power imbalances with health workers. COVID-19 created additional barriers related to social distancing, mask requirements, supply chain challenges and disrupted outreach services. For most caregivers, dropout becomes increasingly likely with compounding barriers. Caregivers of fully-vaccinated children noted facilitators, including accompaniment to health facilities or assistance caring for other children, which enabled them to complete vaccination. CONCLUSIONS: Overcoming immunisation barriers requires strengthening health systems, including improving logistics to avert vaccine stockouts and building health worker capacity, including empathic communication with caregivers. Consistent and reliable immunisation outreach services could address access challenges and improve immunisation uptake, particularly in distant communities.

Test battery designed to quickly and safely assess diverse indices of neuromuscular function after unweighting.

Adequately describing the functional consequences of unweighting (e.g., bed rest, immobilization, spaceflight) requires assessing diverse indices of neuromuscular function (i.e., strength, power, endurance, central activation, force steadiness). Additionally, because unweighting increases the susceptibility of muscle to damage, testing should consider supplementary safety features. The purpose of this study was to develop a test battery for quickly assessing diverse indices of neuromuscular function. Commercially available exercise equipment was modified to include data acquisition hardware (e.g., force plates, position transducers) and auxiliary safety hardware (e.g., magnetic brakes). Ten healthy, ambulatory subjects (31 ± 5 years, 173 ± 11 cm, 73 ± 14 kg) completed a battery of lower- and upper-body neuromuscular function tests on 3 occasions separated by at least 48 hours. The battery consisted of the following tests, in order: (1) knee extension central activation, (2) knee extension force steadiness, (3) leg press maximal strength, (4) leg press maximal power, (5) leg press power endurance, (6) bench press maximal strength, (7) bench press force steadiness, (8) bench press maximal power, and (9) bench press power endurance. Central activation, strength, rate of force development, maximal power, and power endurance (total work) demonstrated good-to-excellent measurement reliability (SEM = 3-14%; intraclass correlation coefficient [ICC] = 0.87-0.99). The SEM of the force steadiness variables was 20-35% (ICC = 0.20-0.60). After familiarization, the test battery required 49 ± 6 minutes to complete. In conclusion, we successfully developed a test battery that could be used to quickly and reliably assess diverse indices of neuromuscular function. Because the test battery involves minimal eccentric muscle actions and impact forces, the potential for muscle injury has likely been reduced.

Integration of health solutions into government systems: a tool for assessing readiness.

Government partnerships are essential for many health solutions to sustain impact at scale, particularly in low-resource settings where strengthening health systems is critical for Universal Health Coverage. Many non-governmental organizations (NGOs) and funders ultimately want solutions to be integrated into public health systems by transitioning solution ownership, management and/or operation to government. However, NGOs and their government partners have limited guidance on how to effectively determine when a solution is ready to transition in a way that will maintain impact long term. To address this need, VillageReach developed the Transition Readiness Assessment (TRA) based on our transition to government theoretical framework. The framework was developed to define both factors related to a solution, as well as external influences that affect a solution's success.  The framework identifies seven dimensions of solution readiness: the political, economic, and social context; solution design; resource availability; financial management; government strategy; government policy and regulations; and organizational management. The TRA measures those dimensions and assigns each one a readiness score. We developed the framework and TRA for VillageReach solutions, as well as to share with government partners and stakeholders. This Open Letter outlines the TRA development, details empirical examples from applying the tool on two VillageReach solutions, and presents recommendations based on our lessons learned. Stakeholders working to transition solutions to government can utilize both the TRA and our lessons.