The need for primary care providers in the clinical management of hypermobility spectrum disorders and ehlers-danlos syndrome: a call to action.

Patients with joint-hypermobility and joint-hypermobility spectrum disorders (HSD), including hypermobile Ehlers-Danlos Syndromes (EDS) present numerous co-morbid concerns, and multidisciplinary care has been recommended. The complexity of these patient's needs and increased demand for medical services have resulted in long delays for diagnosis and treatment and exhausted extant clinical resources. Strategies must be considered to ensure patient needs are met in a timely fashion. This opinion piece discusses several potential models of care for joint-hypermobility disorders, several ways in which primary providers can be involved, and argues that primary providers should be an essential and integrated part of the management of these patients, in collaboration with multidisciplinary teams and pediatric subspecialists. We review several strategies and educational opportunities that may better incorporate primary providers into the care and management of these patients, and we also discuss some of the limitations and barriers that need to be addressed to improve provision of care. This includes establishing primary care physicians as the medical home, providing initial diagnostic and treatment referrals while connecting patients with specialty care, and collaboration and coordination with multi-disciplinary teams for more complex needs. Several barriers exist that may hamper these efforts, including a lack of available specialty trainings for providers interested in providing care to patients with EDS and HSD, a lack of expertly derived consensus guidelines, and limited time resources in extant primary care practices. Also, primary providers should have an active voice in the future for the further consideration and development of these presented strategies.

Self-Recording of Eye Movements in Amyotrophic Lateral Sclerosis Patients Using a Smartphone Eye-Tracking App.

Introduction: Amyotrophic lateral sclerosis (ALS) can affect various eye movements, making eye tracking a potential means for disease monitoring. In this study, we evaluated the feasibility of ALS patients self-recording their eye movements using the "EyePhone," a smartphone eye-tracking application. Methods: We prospectively enrolled ten participants and provided them with an iPhone equipped with the EyePhone app and a PowerPoint presentation with step-by-step recording instructions. The goal was for the participants to record their eye movements (saccades and smooth pursuit) without the help of the study team. Afterward, a trained physician administered the same tests using video-oculography (VOG) goggles and asked the participants to complete a questionnaire regarding their self-recording experience. Results: All participants successfully completed the self-recording process without assistance from the study team. Questionnaire data indicated that participants viewed self-recording with EyePhone favorably, considering it easy and comfortable. Moreover, 70% indicated that they prefer self-recording to being recorded by VOG goggles. Conclusion: With proper instruction, ALS patients can effectively use the EyePhone to record their eye movements, potentially even in a home environment. These results demonstrate the potential for smartphone eye-tracking technology as a viable and self-administered tool for monitoring disease progression in ALS, reducing the need for frequent clinic visits.

Patient and Parent Knowledge, Understanding, and Concerns After a New Diagnosis of Ehlers Danlos Syndrome.

Introduction: After diagnosis of Ehlers Danlos Syndrome (EDS), it is unclear what information patients and parents need and understand about EDS. The objective of this study is to characterize patient and parent knowledge and concerns about EDS after a diagnosis of EDS is made to determine patient and parent concerns and identify barriers that cause discomfort with the diagnosis. Methods: A convenience sample of patient and parent dyads were recruited after new diagnosis of EDS. Patients and parents completed questionnaires that assessed knowledge, comfort, and barriers of EDS before and after diagnosis, EDS education materials accessed, and additional clinical needs and concerns. Results: Seventy-two dyads completed the survey. Conclusion: Many respondents actively seek information on the diagnosis and management of EDS. Parents and patients look for information about EDS differently. Parents have more concerns after diagnosis and both want well-constructed, empirically supported educational materials delivered via multiple modalities, which makes clinical guidelines more essential.

Long-Acting Injectable ART in Practice: A Mixed Methods Implementation Study Assessing the Feasibility of Using LAI ART in High Risk Populations and At Alternative Low Barrier Care Sites.

Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to change the lives of people living with HIV (PLWH). To ensure equitable access to new treatment modalities, we examined the feasibility and acceptability of administering Cabotegravir Rilpivirine Long Acting (CAB/RPV LA) to individuals who experience challenging social determinants of health (SDoH) and struggle with adherence to traditional oral ART. Quantitative and qualitative data were used to assess feasibility of utilizing ART at alternative clinic. Data were collected on individuals eligible to receive CAB/RPV LA at an alternative street-based clinic and on individuals receiving CAB/RPV LA at a traditional HIV clinic. After 6 months, participants were interviewed about their experience. Providers involved in the implementation were also interviewed about their experiences. Only one participant (out of 5) who received CAB/RPV LA at the alternative clinic received consistent treatment, whereas 17 out of 18 participants receiving CAB/RPV LA at the traditional clinic site were adherent. Participants and providers believed that LAI had potential for making treatment adherence easier, but identified several barriers, including discrepancies between patients' desires and their lifestyles, impact of LAI on interactions with the medical system, risk of resistance accompanying sub-optimal adherence, and need for a very high level of resources. While LAI has major potential benefits for high-risk patients, these benefits must be balanced with the complexities of implementation. Despite challenges that impacted study outcomes, improving treatment outcomes for PLWH requires addressing SDoH and substance use.

Narrative review: Revised Principles and Practice Recommendations for Adolescent Substance Use Treatment and Policy.

OBJECTIVE: In 2014, the U.S. National Institute on Drug Abuse released the "Principles of Adolescent Substance Use Disorder Treatment," summarizing previously established evidence and outlining principles of effective assessment, treatment, and aftercare for substance use disorders (SUD). Winters et al. (2018) updated these principles to be developmentally appropriate for adolescents. This review builds on that formative work and recommends updated adolescent assessment, treatment, and aftercare principles and practices. METHOD: The Cochrane, MEDLINE-PubMed, and PsychInfo databases were searched for relevant studies with new data about adolescent substance use services. This article updates the 13 original principles; condenses the 8 original modalities into 5 practices; and highlights implications for public policy approaches, future funding, and research. RESULTS: Key recommendations from the principles include integrating care for co-occurring mental health disorders and SUDs, improving service accessibility including through the educational system, maintaining engagement, and addressing tension between agencies when collaborating with other youth service systems. Updates to the treatment practices include adoption of Screening, Brief Intervention and Referral to Treatment (SBIRT), investment in social programs and family involvement in treatment, expanding access to behavioral therapies and medications, increasing funding to harm reduction services, supporting reimbursement for continuing care services, and increasing investment in research. CONCLUSION: These revised principles of adolescent assessment, treatment, and aftercare approaches and practices aim to establish guidance and evidence-based practices for treatment providers, while encouraging necessary support from policymakers and funding agencies to improve the standard of care for adolescent SUD services.

Equity and unmet need of non-communicable diseases services in Saudi Arabia using a National Household Survey (2019).

BACKGROUND: Saudi Arabia is implementing a comprehensive health system transformation in health services provision, governance, and financing. Given the high burden of non-communicable diseases (NCD), a key objective of the transformation is to integrate NCD prevention and treatment into primary care. The study objectives were to assess primary care service use for treatment of NCDs, to quantify existing inequities in preventive services utilization, and to identify regional and sociodemographic factors associated with these inequities. METHODS: Using the 2019 Kingdom of Saudi Arabia World Health Survey, multivariable logistic regression models were conducted to identify predictors of utilization of primary care services for NCD prevention and treatment, unmet need among those with a diagnosis of diabetes, hypertension, or dyslipidemia, and unmet need in breast and cervical cancer screening. RESULTS: Among those with an NCD diagnosis, living in a high-income household was associated with a lower probability of having an unmet need compared to those in low-income households. Furthermore, rural residents were less likely to have an unmet need compared to urban residents (OR 0.58, p=0.029). Individuals without a perceived need for healthcare within the last 12 months had three times the probability of unmet need in comparison to those with such a perceived need (p<0.001). Women in all regions had a lower probability of ever having a mammogram compared to women in the central regions around Riyadh. Women with an education above a secondary level had five times the odds of undergoing cervical cancer screening and three times the likelihood of ever having a mammogram (P=0.012, p=0.02) than other women. Compared to women in low-income households, those in middle (OR 1.99, P=0.026), upper middle (OR 3.47, p<0.001), or high-income households (OR 2.59, p<0.001) had a higher probability of having had cervical cancer screening. CONCLUSIONS: Inequities in NCD treatment and prevention services' utilization in Saudi Arabia are strongly associated with region of living, population density, wealth, income, education and perceived need for health care. More research is needed to better understand the extent of unmet primary care needs for NCD and how to address the underlying contributing factors to access inequities.

Mollusc and crustacean consumption in the first 1000 days: a scoping review.

Mollusc and crustacean consumption in the first 1000 d may improve maternal and child health by providing essential nutrients. However, in some contexts, molluscs and crustaceans have been associated with allergies and environmental contamination, potentially leading to adverse health and development outcomes. It is unclear whether the health benefits of consuming molluscs and crustaceans, collectively classified as shellfish in nutrition, are outweighed by the potential risks to pregnant women and children. We conducted a scoping review (PROSPERO: CRD42022320454) in PubMed, Scopus and EBSCO Global Health of articles published between January 2000 and March 2022 that assessed shellfish consumption during pregnancy, lactation or childhood (0-2 years) in relation to maternal health, child health or child development. A total of forty-six articles were included in this review. Overall, shellfish consumption was associated with higher biomarkers of environmental contaminants, with mercury being the most studied and having the strongest evidence base. The limited research on nutritional biomarker status shows an association between shellfish consumption and iodine status. Preterm birth was not associated with shellfish consumption, but newborn anthropometry showed mixed results, with several studies reporting lower birth weight with higher shellfish consumption. The few studies that examined child development and maternal health outcomes reported no significant associations. This review revealed trade-off health risks and benefits with inclusion of molluscs and crustaceans in the dietary patterns of mothers and young children. More research is needed to understand how these aquatic animal-source foods may be safely consumed and leveraged for improving human nutrition.

Real-time genomic epidemiologic investigation of a multispecies plasmid-associated hospital outbreak of NDM-5-producing Enterobacterales infections.

OBJECTIVES: New Delhi metallo-ß-lactamase (NDM) is an emergent mechanism of carbapenem resistance associated with high mortality and limited treatment options. Because the blaNDM resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks. METHODS: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance performed weekly. To resolve NDM-encoding plasmids, we performed long-read sequencing and constructed hybrid assemblies. WGS data for suspected outbreaks was shared with the IP&C team for assessment and intervention. RESULTS: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included 7 bacterial species encoding the same NDM-5 plasmid. WGS surveillance and epidemiologic investigation characterized 10 horizontal plasmid transfer events and 6 bacterial transmission events between patients in varying hospital units. CONCLUSIONS: Our investigation revealed a complex, multispecies outbreak of NDM involving multiple plasmid transfer and bacterial transmission events. We highlight the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks.

Investigation of patients' understanding of fibromyalgia: Results from an online qualitative survey.

OBJECTIVE: An important component to effective fibromyalgia treatment is patient education about the condition. While previous educational interventions have been developed, these have not incorporated the lived experiences of patients and may not address common misunderstandings among those who may benefit from these interventions. This study aimed to explore understanding, confusion, and gaps in knowledge about fibromyalgia among those who report a fibromyalgia diagnosis. METHODS: Participants were recruited via clinic flyers and the social media page of a chronic pain research laboratory. Participants completed an online survey that assessed their knowledge of fibromyalgia via open-ended questions. Responses were analyzed via thematic analysis to identify, analyze, and report themes. RESULTS: Thirty-eight participants completed the survey (63% female, ages 18-68). Common themes that arose from patients included being unsure of the cause of their fibromyalgia, frustration and confusion about the random/variable nature of symptoms and flares, feeling that their condition was invisible, and desiring more information on available treatments. CONCLUSION: Participants in this study expressed confusion about many aspects of fibromyalgia and a desire for more understanding from others in their life about this condition. PRACTICE IMPLICATIONS: Future interventions would benefit from tailoring fibromyalgia education to the specific knowledge and lived experiences of patients.

Associations of fish and meat intake with iron and anaemia in Malawian children.

Animal flesh foods are rich in bioavailable iron but infrequently consumed by young children. We aimed to determine whether flesh food intake was associated with iron and anaemia status among 585 Malawian infants enroled in a 6-month egg-feeding trial. The percentage of days of small fish, large fish and meat consumption were assessed through weekly 7-day animal-source food screeners. Grams of intake were assessed through 24-h recalls conducted at 6-9, 9-12 and 12-15 months of age. Plasma ferritin, soluble transferrin receptor (sTfR) and haemoglobin concentrations were measured at 6-9 and 12-15 months of age. Iron biomarkers were adjusted for inflammation during analysis. At enrolment, each flesh food category was consumed by <5% of children in the past 24 h. Over the next 6 months, small fish, large fish and meat were consumed on 25%, 8% and 6% of days, respectively, with mean usual intakes of <5 g/day. More frequent small fish consumption was associated with lower sTfR (geometric mean ratio [95% CI]: 0.98 mg/L [0.96, 1.00] per 10 percentage point difference) but not ferritin (1.03 µg/L [0.98, 1.07]) or haemoglobin (1.01 g/dL [1.00, 1.01]). Large fish consumption was associated with higher anaemia (prevalence ratio [95% CI]: 1.09 [1.01, 1.19]) and lower iron deficiency (0.96 [0.93, 1.00]) prevalence. Gram intakes of flesh food categories were not associated with any iron or anaemia indicators. Small fish were a primary contributor to flesh food intake in this cohort of Malawian children, although usual portions were small. Fish was associated with modest improvements to iron status, but meat was too infrequent to be associated with anaemia and iron deficiency.

Sensory panel results of a dried fish powder supplement among caregivers and young children in Zambia.

OBJECTIVE: To evaluate the acceptability of traditional Zambian dishes fortified with Complementary Food for Africa+Dried Fish Powder (ComFA+Fish), a locally sourced protein/micronutrient blend designed to impact nutrient deficiencies among infants and young children (IYC) and improve pregnancy and birth outcomes among women of reproductive age (WRA). DESIGN: During two sensory panels, caregivers evaluated: (1) the acceptability of four ComFA+Fish dishes for household consumption, including fortified chibwabwa fisashi, savory Kapenta chutney, fortified complementary maize porridge and fortified bean-vegetable soup and (2) whether their IYC found the fortified complementary maize porridge acceptable. SETTING: Lake Kariba, Southern Province, Zambia. PARTICIPANTS: Women of reproductive age (n 42) and their IYC aged 6-11 months (n 16) and 12-23 months (n 26) were recruited from fishing villages in Gwembe, Siavonga and Sinazongwe District. RESULTS: A majority of caregivers extremely liked/liked the: (1) fortified chibwabwa fisashi's sensory attributes (94·7 %), convenience (92·8 %) and overall acceptability (100 %); (2) savory Kapenta chutney's sensory attributes (81·8 %), convenience (92·8 %) and overall acceptability (100 %); (3) fortified complementary porridge's sensory attributes (83·5 %), convenience (90·5 %) and overall acceptability (88·1 %) and (4) fortified bean-vegetable soup's sensory attributes (66·8 %), convenience (87·5 %) and overall acceptability (87·5 %). Further, a majority of caregivers evaluated the fortified complementary porridge as highly acceptable to their IYC. CONCLUSIONS: Results suggest that ComFA+Fish is strategically well placed to fill nutritional gaps among IYC and WRA in Zambia and has the potential to be scaled across sub-Saharan Africa.

Barriers to the Diagnosis, Care, and Management of Pediatric Patients With Ehlers-Danlos Syndrome in the United States: A Qualitative Analysis.

Objectives: Ehlers-Danlos Syndromes (EDS) are a family of heritable connective tissue diseases. Primary practitioners are capable of diagnosing and managing EDS; however, few are knowledgeable and comfortable enough to see patients with EDS, resulting in delays in diagnosis and care. This study explores the barriers physicians experience with diagnosing, managing, and caring for patients with EDS, and potential resolutions to those barriers. Methods: As part of a larger online study, providers (n = 107) in the United States were asked to specify "What information would improve (their) comfort" in diagnosing, caring for, and managing EDS via open-ended questions. Results: Providers reported wanting clinical practice guidelines, in formats that were easily accessible and usable, information on their roles in the management of EDS, the best ways to coordinate with specialty care, and available specialty consultation. Conclusions: Providers overall are willing to diagnose and treat EDS; however, additional supports and training are needed.

Stable Decoding from a Speech BCI Enables Control for an Individual with ALS without Recalibration for 3 Months.

Brain-computer interfaces (BCIs) can be used to control assistive devices by patients with neurological disorders like amyotrophic lateral sclerosis (ALS) that limit speech and movement. For assistive control, it is desirable for BCI systems to be accurate and reliable, preferably with minimal setup time. In this study, a participant with severe dysarthria due to ALS operates computer applications with six intuitive speech commands via a chronic electrocorticographic (ECoG) implant over the ventral sensorimotor cortex. Speech commands are accurately detected and decoded (median accuracy: 90.59%) throughout a 3-month study period without model retraining or recalibration. Use of the BCI does not require exogenous timing cues, enabling the participant to issue self-paced commands at will. These results demonstrate that a chronically implanted ECoG-based speech BCI can reliably control assistive devices over long time periods with only initial model training and calibration, supporting the feasibility of unassisted home use.

Comparing organization-focused and state-focused financing strategies on provider-level reach of a youth substance use treatment model: a mixed-method study.

BACKGROUND: Financial barriers in substance use disorder service systems have limited the widespread adoption-i.e., provider-level reach-of evidence-based practices (EBPs) for youth substance use disorders. Reach is essential to maximizing the population-level impact of EBPs. One promising, but rarely studied, type of implementation strategy for overcoming barriers to EBP reach is financing strategies, which direct financial resources in various ways to support implementation. We evaluated financing strategies for the Adolescent Community Reinforcement Approach (A-CRA) EBP by comparing two US federal grant mechanisms, organization-focused and state-focused grants, on organization-level A-CRA reach outcomes. METHOD: A-CRA implementation took place through organization-focused and state-focused grantee cohorts from 2006 to 2021. We used a quasi-experimental, mixed-method design to compare reach between treatment organizations funded by organization-focused versus state-focused grants (164 organizations, 35 states). Using administrative training records, we calculated reach as the per-organization proportion of trained individuals who received certification in A-CRA clinical delivery and/or supervision by the end of grant funding. We tested differences in certification rate by grant type using multivariable linear regression models that controlled for key covariates (e.g., time), and tested threats to internal validity from our quasi-experimental design through a series of sensitivity analyses. We also drew on interviews and surveys collected from the treatment organizations and (when relevant) interviews with state administrators to identify factors that influenced reach. RESULTS: The overall certification rates were 27 percentage points lower in state-focused versus organization-focused grants (p = .01). Sensitivity analyses suggested these findings were not explained by confounding temporal trends nor by organizational or state characteristics. We did not identify significant quantitative moderators of reach outcomes, but qualitative findings suggested certain facilitating factors were more influential for organization-focused grants (e.g., strategic planning) and certain barrier factors were more impactful for state-focused grants (e.g., states finding it difficult to execute grant activities). DISCUSSION: As the first published comparison of EBP reach outcomes between financing strategies, our findings can help guide state and federal policy related to financing strategies for implementing EBPs that reduce youth substance use. Future work should explore contextual conditions under which different financing strategies can support the widespread implementation of EBPs for substance use disorder treatment.

Seroprevalence Study of Conserved Enterotoxigenic Escherichia coli Antigens in Globally Diverse Populations.

Enterotoxigenic Escherichia coli (ETEC) are common causes of infectious diarrhea among young children of low-and middle-income countries (LMICs) and travelers to these regions. Despite their significant contributions to the morbidity and mortality associated with childhood and traveler's diarrhea, no licensed vaccines are available. Current vaccine strategies may benefit from the inclusion of additional conserved antigens, which may contribute to broader coverage and enhanced efficacy, given their key roles in facilitating intestinal colonization and effective enterotoxin delivery. EatA and EtpA are widely conserved in diverse populations of ETEC, but their immunogenicity has only been studied in controlled human infection models and a population of children in Bangladesh. Here, we compared serologic responses to EatA, EtpA and heat-labile toxin in populations from endemic regions including Haitian children and subjects residing in Egypt, Cameroon, and Peru to US children and adults where ETEC infections are sporadic. We observed elevated IgG and IgA responses in individuals from endemic regions to each of the antigens studied. In a cohort of Haitian children, we observed increased immune responses following exposure to each of the profiled antigens. These findings reflect the wide distribution of ETEC infections across multiple endemic regions and support further evaluation of EatA and EtpA as candidate ETEC vaccine antigens.

Genomic Epidemiologic Investigation of a Multispecies Hospital Outbreak of NDM-5-Producing Enterobacterales Infections.

Background: New Delhi metallo-ß-lactamase (NDM) represents an emergent mechanism of carbapenem resistance associated with high mortality and limited antimicrobial treatment options. Because the blaNDM resistance gene is often carried on plasmids, traditional infection prevention and control (IP&C) surveillance methods like speciation, antimicrobial resistance testing, and reactive whole genome sequencing (WGS) may not detect plasmid transfer in multispecies outbreaks. Methods: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance, which was performed weekly using the Illumina platform. To resolve NDM-encoding plasmids, we performed long-read Oxford Nanopore sequencing and constructed hybrid assemblies using Illumina and Nanopore sequencing data. Reports of relatedness between NDM-producing organisms and reactive WGS for suspected outbreaks were shared with the IP&C team for assessment and intervention. Findings: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included seven bacterial species and each encoded the same NDM-5 plasmid, which showed high homology to NDM plasmids previously observed in Asia. WGS surveillance and epidemiologic investigation characterized ten horizontal plasmid transfer events and six bacterial transmission events between patients housed in varying hospital units. Transmission prevention focused on enhanced observation and adherence to basic infection prevention measures. Interpretation: Our investigation revealed a complex, multispecies outbreak of NDM that involved multiple plasmid transfer and bacterial transmission events, increasing the complexity of outbreak identification and transmission prevention. Our investigation highlights the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks. Funding: This work was funded in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (R01AI127472) (R21AI1783691).

Protocol for an evaluation of adherence monitoring and support interventions among people initiating antiretroviral therapy in Cape Town, South Africa-a multiphase optimization strategy (MOST) approach using a fractional factorial design.

BACKGROUND: South Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed. Standard care only allows for suboptimal adherence detection when routine testing indicates unsuppressed virus. Several adherence interventions are known to improve HIV outcomes, yet few are implemented in routinely due to the resources required. Therefore, determining scalable evidence-based adherence support interventions for resource-limited settings (RLS) is a priority. The multiphase optimization strategy (MOST) framework allows for simultaneous evaluation of multiple intervention components and their interactions. We propose to use MOST to identify the intervention combination with the highest levels of efficacy and cost-effectiveness that is feasible and acceptable in primary care clinics in Cape Town. METHODS: We will employ a fractional factorial design to identify the most promising intervention components for inclusion in a multi-component intervention package to be tested in a future randomized controlled trial. We will recruit 512 participants initiating ART between March 2022 and February 2024 in three Cape Town clinics and evaluate acceptability, feasibility, and cost-effectiveness of intervention combinations. Participants will be randomized to one of 16 conditions with different combinations of three adherence monitoring components: rapid outreach following (1) unsuppressed virus, (2) missed pharmacy refill collection, and/or (3) missed doses as detected by an electronic adherence monitoring device; and two adherence support components: (1) weekly check-in texts and (2) enhanced peer support. We will assess viral suppression (<50 copies/mL) at 24 months as the primary outcome; acceptability, feasibility, fidelity, and other implementation outcomes; and cost-effectiveness. We will use logistic regression models to estimate intervention effects with an intention-to-treat approach, employ descriptive statistics to assess implementation outcomes, and determine an optimal intervention package. DISCUSSION: To our knowledge, ours will be the first study to use the MOST framework to determine the most effective combination of HIV adherence monitoring and support intervention components for implementation in clinics in a RLS. Our findings will provide direction for pragmatic, ongoing adherence support that will be key to ending the HIV epidemic. TRIAL REGISTRATION: ClinicalTrials.gov NCT05040841. Registered on 10 September 2021.

Low Temperature Delays the Effects of Ischemia in Bergmann Glia and in Cerebellar Tissue Swelling.

Cerebral ischemia results in oxygen and glucose deprivation that most commonly occurs after a reduction or interruption in the blood supply to the brain. The consequences of cerebral ischemia are complex and involve the loss of metabolic ATP, excessive K+ and glutamate accumulation in the extracellular space, electrolyte imbalance, and brain edema formation. So far, several treatments have been proposed to alleviate ischemic damage, yet few are effective. Here, we focused on the neuroprotective role of lowering the temperature in ischemia mimicked by an episode of oxygen and glucose deprivation (OGD) in mouse cerebellar slices. Our results suggest that lowering the temperature of the extracellular 'milieu' delays both the increases in [K+]e and tissue swelling, two dreaded consequences of cerebellar ischemia. Moreover, radial glial cells (Bergmann glia) display morphological changes and membrane depolarizations that are markedly impeded by lowering the temperature. Overall, in this model of cerebellar ischemia, hypothermia reduces the deleterious homeostatic changes regulated by Bergmann glia.

The Effects of One Egg Per Day on Vitamin A Status Among Young Malawian Children: A Secondary Analysis of a Randomized Controlled Trial.

Background: Vitamin A deficiency (VAD) is common in populations with limited dietary diversity and access to vitamin A-rich foods. Objectives: This analysis aimed to determine the impact of supplementing children's diets with 1 egg/d on the concentration of plasma retinol and RBP and the prevalence of VAD. Methods: Children age 6-9 mo living in the Mangochi district of Malawi were individually randomly assigned to receive 1 egg/d for 6 mo (n = 331) or continue their usual diet (n = 329) in the Mazira trial (clinicaltrials.gov; NCT03385252). This secondary analysis measured plasma retinol by HPLC and RBP, CRP, and α-1-acid glycoprotein (AGP) by ELISA techniques at enrollment and 6 mo follow-up. Retinol and RBP were adjusted for inflammation, and mean concentrations were compared between groups using linear regression models. In addition, prevalence ratios of VAD (retinol <0.7 µmol/L) were compared between groups using log-binomial or modified Poisson regression models. Results: After 6 mo of study participation, 489 were assessed for retinol (egg: n = 238; control: n = 251), and 575 (egg: n = 281; control: n = 294) were assessed for RBP. Prevalence of inflammation (CRP >5 mg/L or AGP >1 g/L: 62%) and inflammation-adjusted VAD (7%) at enrollment did not differ between groups. At follow-up, the egg intervention group did not differ from the control in inflammation-adjusted retinol [geometric mean (95% CI); egg: 1.10 µmol/L (1.07, 1.13); control: 1.08 (1.05, 1.12)], RBP [egg: 0.99 µmol/L (0.96, 1.02); control: 0.97 (0.94, 1.00)], or prevalence of VAD [egg: 6%; control: 3%; prevalence ratio: 1.87 (0.83, 4.24)]. Conclusions: Provision of 1 egg/d did not impact VAD, plasma retinol, or RBP among young children in rural Malawi, where the prevalence of VAD was low. Curr Dev Nutr 2023;x:xx.This trial was registered at [clinicaltrials.gov] as [NCT03385252].

Prevalence of diarrheagenic Escherichia coli and impact on child health in Cap-Haitien, Haiti.

BACKGROUND: Diarrheagenic Escherichia coli (DEC) are common pathogens infecting children during their growth and development. Determining the epidemiology and the impact of DEC on child anthropometric measures informs prioritization of prevention efforts. These relationships were evaluated in a novel setting, Cap-Haitien, Haiti. METHODS: We performed pre-specified secondary analysis of a case-control study of community-dwelling children, 6-36 months of age, enrolled 96 cases with diarrhea and 99 asymptomatic controls. Assessments were performed at enrollment and one month later at follow-up. Established endpoint PCR methodologies targeted DEC gDNA isolated from fecal swabs. The association between DEC and anthropometric z-scores at enrollment was determined using multivariate linear regression. Lastly, we assessed the association between specific biomarkers, choline and docosahexaenoic acid (DHA) and diarrheal burden. RESULTS: Enterotoxigenic Escherichia coli (ETEC) was identified in 21.9% of cases vs. 16.1% of controls with heat-stable producing ETEC significantly associated with symptomatic disease. Enteroaggregative E. coli (EAEC) was found in 30.2% of cases vs. 27.3% of controls, and typical enteropathogenic E. coli in 6.3% vs. 4.0% of cases and controls, respectively. Multivariate linear regression, controlled for case or control status, demonstrated ETEC and EAEC were significantly associated with reduced weight-age z-score (WAZ) and height-age z-score (HAZ) after adjusting for confounders. An interaction between ETEC and EAEC was observed. Choline and DHA were not associated with diarrheal burden. CONCLUSIONS: DEC are prevalent in north Haitian children. ETEC, EAEC, household environment, and diet are associated with unfavorable anthropometric measures, with possible synergistic interactions between ETEC and EAEC. Further studies with longer follow up may quantify the contribution of individual pathogens to adverse health outcomes.