Magnification in preclinical procedures: effect on muscle activity and angular deviations of the neck and trunk.

Objectives: This study aimed to assess the effects of different magnification systems on the angular deviations of the neck and trunk and the muscle activities of the upper back and neck during preclinical cavity preparation. Methods: This was an experimental laboratory study, with the angular deviations from the neutral positions of the neck and trunk and the activities of the bilateral upper back (the descending and ascending trapezius) and neck (sternocleidomastoid) muscles as the dependent variables. The independent variables were the different magnification systems used (Simple, Galilean, and Keplerian loupes, with direct vision as the control) and prepared teeth (teeth 16, 26, 36, and 46). A dental mannequin phantom head with artificial resin teeth was used, and Class I cavity preparations for composite resin were performed on teeth 16, 26, 36, and 46 using a 1012 round diamond bur at low speed. To analyze the angular deviations, the postures adopted during the procedure were recorded using a tripod-mounted camera positioned to provide a lateral view of the operator. A trained researcher measured the angular deviations using the software entitled "Software for Postural Assessment"-SAPO (version 0.69). Bilateral muscle activity was assessed using surface electromyography. Descriptive statistical analysis was performed, and after verifying the assumptions of normality and homoscedasticity, two-way analysis of variance and the Tukey and Games-Howell post-hoc tests were used to compare the data (α=0.05). Results: The angular deviation from the neutral position of the neck was found to be significantly higher during cavity preparations performed with the naked eye and the Simple loupe, irrespective of the prepared tooth. With regard to tooth location, the angular deviation of the neck was significantly greater during cavity preparation on teeth 16 and 26, and the angular deviation of the trunk was significantly greater during cavity preparation on tooth 26, regardless of the magnification system used. There were significant differences in right sternocleidomastoid muscle activity between the Simple, Galilean, and Keplerian loupes, with activity being the lowest for the Galilean loupe (p = 0.008). There were no significant differences in left sternocleidomastoid muscle activity between the loupes, regardless of the prepared tooth (p = 0.077). The activities of the bilateral descending trapezius and the right ascending trapezius muscles were significantly lower when the Galilean loupe was used (p < 0.010). Conclusion: These results suggest that the Galilean loupe resulted in lower muscle activity in the neck and back regions and that the Galilean and Keplerian loupes resulted in less angular deviations of the neck and trunk during cavity preparation.

Influence of lower limb isokinetic muscle strength and power on the occurrence of falls in community-dwelling older adults: A longitudinal study.

INTRODUCTION: Previous studies have highlighted the association between lower limb muscle strength and falls in older adults. However, a comprehensive understanding of the specific influence of each lower limb muscle group on fall occurrences remains lacking. OBJECTIVE: This study aimed to investigate the impact of knee, ankle, and hip muscle strength and power on falls in older adults, with the goal of identifying which muscle groups are more predictive of fall risk in this population. METHODS: This longitudinal observational study enrolled 94 community-dwelling older adults. Muscle strength and power of the ankle's plantiflexors and dorsiflexors, knee flexors and extensors, and hip flexors, extensors, adductors, and abductors were assessed using a Biodex System 4 Pro® isokinetic dynamometer. Fall occurrences were monitored through monthly telephone contact over a year. RESULTS: Participants, with a median age of 69 years (range 64-74), included 67% women, and 63.8% reported a sedentary lifestyle. Among them, 45,7% of older adults were classified as fallers. Comparative analyses revealed that non-fallers displayed significantly superior isokinetic muscle strength in the hip abductors and adductors, along with higher muscle power in the hip abductors, hip flexors, and knee flexors compared to fallers. Multivariate logistic regression analysis indicated that a 1 Nm/Kg increase in hip abductor strength reduced the chance of a fall by 86.3%, and a 1 Watt increase in hip flexor power reduced the chance of a fall by 3.6%. CONCLUSION: The findings indicate that hip abductor strength and hip flexor power can be considered protective factors against falls in independent older adults in the community. These findings may contribute to developing effective fall-prevention strategies for this population.

Predictors of the Outcome at 2 Years in Neonates With Congenital Cytomegalovirus Infection.

BACKGROUND: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes. METHODS: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests. RESULTS: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96). CONCLUSIONS: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate.

An Emergent Change in Epidemiologic and Microbiological Characteristics of Bloodstream Infections in Adults With Febrile Neutropenia Resulting From Chemotherapy for Acute Leukemia and Lymphoma at Reference Centers in Chile, Ecuador, and Peru.

Background: Febrile neutropenia is a life-threatening condition commonly observed in patients with hematologic malignancies. The aim of this article is to provide updated knowledge about bloodstream infections in febrile neutropenia episodes within the Andean region of Latin America. Method: This retrospective study was based in 6 hospitals in Chile, Ecuador, and Peru and included adult patients with acute leukemia or lymphoma and febrile neutropenia between January 2019 and December 2020. Results: Of the 416 febrile neutropenia episodes, 38.7% had a bloodstream infection, 86% of which were caused by gram-negative rods, with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently identified bacteria. K pneumoniae isolates were more frequently resistant than E coli to cefotaxime (65% vs 39.6%), piperacillin-tazobactam (56.7% vs 27.1%), and imipenem (35% vs 2.1%) and were more frequently multidrug resistant (61.7% vs 12.5%). Among P aeruginosa, 26.7% were resistant to ceftazidime, piperacillin-tazobactam, and imipenem, and 23.3% were multidrug resistant. Overall 30-day mortality was 19.8%, being higher with vs without a bloodstream infection (26.7% vs 15.3%, P = .005). Fever duration was also significantly longer, as well as periods of neutropenia and length of hospital stay for patients with bloodstream infection. Additionally, the 30-day mortality rate was higher for episodes with inappropriate vs appropriate empirical antibiotic therapy (41.2% vs 26.6%, P = .139). Conclusions: Considering the high rates of bacteria-resistant infection and 30-day mortality, it is imperative to establish strategies that reduce the frequency of bloodstream infections, increasing early identification of patients at higher risks of multidrug bacteria resistance, and updating existing empirical antibiotic recommendations.

Genomic characterisation of the population structure and antibiotic resistance of Salmonella enterica serovar Infantis in Chile, 2009-2022.

Background: Multidrug-resistant (MDR) Salmonella Infantis has disseminated worldwide, mainly linked to the consumption of poultry products. Evidence shows dissemination of this pathogen in Chile; however, studies are primarily limited to phenotypic data or involve few isolates. As human cases of Salmonella Infantis infections have substantially increased in recent years, this study aimed to characterise the genomic epidemiology and antimicrobial-resistance profiles of isolates obtained from different sources, aiming to inform effective surveillance and control measures. Methods: We sequenced 396 Salmonella Infantis genomes and analysed them with all publicly available genomes of this pathogen from Chile (440 genomes in total), representing isolates from environmental, food, animal, and human sources obtained from 2009 to 2022. Based on bioinformatic and phenotypic methods, we assessed the population structure, dissemination among different niches, and antimicrobial resistance (AMR) profiles of Salmonella Infantis in the country. Findings: The genomic and phylogenetic analyses showed that Salmonella Infantis from Chile comprised several clusters of highly related isolates dominated by sequence type 32. The HC20_343 cluster grouped an important proportion of all isolates. This was the only cluster associated with pESI-like megaplasmids, and up to 12 acquired AMR genes/mutations predicted to result in an MDR phenotype. Accordingly, antimicrobial-susceptibility testing revealed a strong concordance between the AMR genetic determinants and their matching phenotypic expression, indicating that a significant proportion of HC20_343 isolates produce extended-spectrum ß-lactamases and have intermediate fluoroquinolone resistance. HC20_343 Salmonella Infantis were spread among environmental, animal, food, and human niches, showing a close relationship between isolates from different years and sources, and a low intra-source genomic diversity. Interpretation: Our findings show a widespread dissemination of MDR Salmonella Infantis from the HC20_343 cluster in Chile. The high proportion of isolates with resistance to first-line antibiotics and the evidence of active transmission between the environment, animals, food, and humans highlight the urgency of improved surveillance and control measures in the country. As HC20_343 isolates predominate in the Americas, our results suggest a high prevalence of ESBL-producing Salmonella Infantis with intermediate fluoroquinolone resistance in the continent. Funding: Partially supported by the Food and Drug Administration (FDA) of the U.S. Department of Health and Human Services as part of an award, FDU001818, with 30% percent funded by FDA/HHS; and by Agencia de Investigación y Desarrollo de Chile (ANID) through FONDECYT de Postdoctorado Folio 3230796 and Folio 3210317, FONDECYT Regular Folio 1231082, and ANID-Millennium Science Initiative Program-ICN2021_044.

Use of a footstool improves rectal balloon expulsion in some patients with defecatory disorders.

BACKGROUND: Whether patients with defecatory disorders (DDs) with favorable response to a footstool have distinctive anorectal pressure characteristics is unknown. We aimed to identify the clinical phenotype and anorectal pressure profile of patients with DDs who benefit from a footstool. METHODS: This is a retrospective review of patients with high resolution anorectal manometry (HR-ARM) and balloon expulsion test (BET) from a tertiary referral center. BET was repeated with a 7-inch-high footstool in those who failed it after 120 s. Data were compared among groups with respect to BET results. KEY RESULTS: Of the 667 patients with DDs, a total of 251 (38%) had failed BET. A footstool corrected BET in 41 (16%) of those with failed BET. Gender-specific differences were noted in anorectal pressures, among patients with and without normal BET, revealing gender-based nuances in pathophysiology of DDs. Comparing patients who passed BET with footstool with those who did not, the presence of optimal stool consistency, with reduced instances of loose stools and decreased reliance on laxatives were significant. Additionally, in women who benefited from a footstool, lower anal pressures at rest and simulated defecation were observed. Independent factors associated with a successful BET with a footstool in women included age <50, Bristol 3 or 4 stool consistency, lower anal resting pressure and higher rectoanal pressure gradient. CONCLUSION & INFERENCES: Identification of distinctive clinical and anorectal phenotype of patients who benefited from a footstool could provide insight into the factors influencing the efficacy of footstool utilization and allow for an individualized treatment approach in patients with DDs.

Pathogenic effects of Leu200Pro and Arg387His VRK1 protein variants on phosphorylation targets and H4K16 acetylation in distal hereditary motor neuropathy.

Rare recessive variants in the human VRK1 gene are associated with several motor neuron diseases (MND), such as amyotrophic lateral sclerosis, spinal muscular atrophy, or distal hereditary motor neuropathies (dHMN). A case with dHMN carrying two novel VRK1 gene variants, expressing Leu200Pro (L200P) and Arg387His (R387H) variant proteins, identified that these protein variants are functionally different. The Leu200Pro variant shares with several variants in the catalytic domain the loss of the kinase activity on different substrates, such as histones, p53, or coilin. However, the distal Arg387His variant and the distal Trp375* (W375X) chinese variant, both located at the end of the low complexity C-terminal region and proximal to the termination codon, retain their catalytic activity on some substrates, and mechanistically their functional impairment is different. The L200P variant, as well as most VRK1 pathogenic variants, impairs the phosphorylation of BAF and histone H4K16 acetylation, which are required for DNA attachment to the nuclear envelope and chromatin accessibility to DNA repair mechanisms, respectively. The R387H variant impairs phosphorylation of H2AX, an early step in different types of DNA damage responses. The functional variability of VRK1 protein variants and their different combinations are a likely contributor to the clinical phenotypic heterogeneity of motor neuron and neurological diseases associated with rare VRK1 pathogenic variants. KEY MESSAGES: VRK1 variants implicated in motor neuron diseases are functionally different. The L200P variant is kinase inactive, and the R387H variant is partially active. VRK1 variants alter H4K16 acetylation and loss of coilin and BAF phosphorylation. VRK1 variants alter Cajal bodies and DNA damage responses. VRK1 variant combination determines the neurological phenotype heterogeneity.

Artificial Intelligence-Generated Draft Replies to Patient Inbox Messages.

Importance: The emergence and promise of generative artificial intelligence (AI) represent a turning point for health care. Rigorous evaluation of generative AI deployment in clinical practice is needed to inform strategic decision-making. Objective: To evaluate the implementation of a large language model used to draft responses to patient messages in the electronic inbox. Design, Setting, and Participants: A 5-week, prospective, single-group quality improvement study was conducted from July 10 through August 13, 2023, at a single academic medical center (Stanford Health Care). All attending physicians, advanced practice practitioners, clinic nurses, and clinical pharmacists from the Divisions of Primary Care and Gastroenterology and Hepatology were enrolled in the pilot. Intervention: Draft replies to patient portal messages generated by a Health Insurance Portability and Accountability Act-compliant electronic health record-integrated large language model. Main Outcomes and Measures: The primary outcome was AI-generated draft reply utilization as a percentage of total patient message replies. Secondary outcomes included changes in time measures and clinician experience as assessed by survey. Results: A total of 197 clinicians were enrolled in the pilot; 35 clinicians who were prepilot beta users, out of office, or not tied to a specific ambulatory clinic were excluded, leaving 162 clinicians included in the analysis. The survey analysis cohort consisted of 73 participants (45.1%) who completed both the presurvey and postsurvey. In gastroenterology and hepatology, there were 58 physicians and APPs and 10 nurses. In primary care, there were 83 physicians and APPs, 4 nurses, and 8 clinical pharmacists. The mean AI-generated draft response utilization rate across clinicians was 20%. There was no change in reply action time, write time, or read time between the prepilot and pilot periods. There were statistically significant reductions in the 4-item physician task load score derivative (mean [SD], 61.31 [17.23] presurvey vs 47.26 [17.11] postsurvey; paired difference, -13.87; 95% CI, -17.38 to -9.50; P < .001) and work exhaustion scores (mean [SD], 1.95 [0.79] presurvey vs 1.62 [0.68] postsurvey; paired difference, -0.33; 95% CI, -0.50 to -0.17; P < .001). Conclusions and Relevance: In this quality improvement study of an early implementation of generative AI, there was notable adoption, usability, and improvement in assessments of burden and burnout. There was no improvement in time. Further code-to-bedside testing is needed to guide future development and organizational strategy.

Clinical Trials That Have Changed Clinical Practice and Care of Pregnant People With HIV.

Over the last 4 decades, significant advances in the care of HIV during pregnancy have successfully reduced, and nearly eliminated, the risk of perinatal HIV transmission. The baseline risk of transmission without intervention (25% to 30%) is now <1% to 2% in the United States with contemporary antepartum, intrapartum, and postnatal interventions. In this review, we discuss 3 landmark clinical trials that substantially altered obstetric practice for pregnant individuals with HIV and contributed to this extraordinary achievement: 1) the Pediatric AIDS Clinical Trials Group 076 Trial determined that antepartum and intrapartum administration of antiretroviral drug zidovudine to the pregnant individual, and postnatally to the newborn, could reduce the risk of perinatal transmission by approximately two-thirds; 2) the European Mode of Delivery Collaboration Trial demonstrated performance of a prelabor cesarean birth before rupture of membranes among pregnant people with viremia reduced the risk of perinatal transmission compared with vaginal birth; and 3) the International Maternal Pediatric Adolescent AIDS Clinical Trials Network 2010 Trial identified that dolutegravir-containing, compared with efavirenz-containing, antiretroviral regimens during pregnancy achieved a significantly higher rate of viral suppression at delivery with shorter time to viral suppression, with fewer adverse pregnancy outcomes. Collectively, these trials not only advanced obstetric practice but also advanced scientific understanding of the timing, mechanisms, and determinants of perinatal HIV transmission. For each trial, we will describe key aspects of the study protocol and outcomes, insights gleaned about the dynamics of perinatal transmission, how each study changed clinical practice, and relevant updates to current practice since the trial's publication.

HIV Diagnostics and Vaccines: It Takes Two to Tango.

Current serological tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests that are agnostic to vaccination status (i.e., only positive for true HIV-1 infection) of tested individuals are needed. Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in both vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serological HIV tests for concurrent deployment with HIV vaccines.

Histological evidence of hypothyroidism in mice chronically exposed to conventional farming.

Worldwide, disorders of the thyroid gland are a growing concern; such can be caused by exposure to contaminants, including agrochemicals used in conventional agriculture, which act as endocrine disruptors. The purpose of this study is to evaluate whether or not exposure to an environment with conventional agriculture leads to thyroid disruption. Mus musculus were used as bioindicator species, captured in two sites: a farm where conventional agriculture is practiced, and a place without agriculture. Thyroid histomorphometric and morphologic data were analyzed. The impacts of the agricultural environment over the thyroid were revealed, as indications of hypothyroidism were observed in exposed mice: the area and volume of epithelial cells were much lower. Alterations in thyroid histomorphology were also observed: lower follicular sphericity, irregularly delimited epithelium and increased exfoliation into the colloid. These results highlight the need for transition from current conventional agricultural systems towards organic systems.

Cabergoline as a Novel Strategy for Post-Pregnancy Breast Cancer Prevention in Mice and Human.

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects. Here, we report that cabergoline, a dopaminergic agonist, reduces the risk of breast cancer post-pregnancy in a Brca1/P53-deficient mouse model, with implications for human breast cancer prevention. We show that a single dose of cabergoline administered post-pregnancy significantly delayed the onset and reduced the incidence of breast cancer in Brca1/P53-deficient mice. Histological analysis revealed a notable acceleration in post-lactational involution over the short term, characterized by increased apoptosis and altered gene expression related to ion transport. Over the long term, histological changes in the mammary gland included a reduction in the ductal component, decreased epithelial proliferation, and a lower presence of recombinant Brca1/P53 target cells, which are precursors of tumors. These changes serve as indicators of reduced breast cancer susceptibility. Additionally, RNA sequencing identified gene expression alterations associated with decreased proliferation and mammary gland branching. Our findings highlight a mechanism wherein cabergoline enhances the protective effect of pregnancy against breast cancer by potentiating postlactational involution. Notably, a retrospective cohort study in women demonstrated a markedly lower incidence of post-pregnancy breast cancer in those treated with cabergoline compared to a control group. Our work underscores the importance of enhancing postlactational involution as a strategy for breast cancer prevention, and identifies cabergoline as a promising, low-risk option in breast cancer chemoprevention. This strategy has the potential to revolutionize breast cancer prevention approaches, particularly for women at increased risk due to genetic factors or delayed childbirth, and has wider implications beyond hereditary breast cancer cases.

Effects of physical exercise interventions on balance, postural stability and general mobility in Parkinson's disease: a network meta-analysis.

OBJECTIVE: To assess which type of physical exercise intervention has the most beneficial effects on balance, postural stability and general mobility in patients with Parkinson's disease. These parameters were assessed using the Activities-specific Balance Confidence (ABC) scale, Berg Balance Scale (BBS), Mini-Balance Evaluation Systems Test (MiniBESTest) and Timed Up and Go Test (TUG). DESIGN: Network meta-analysis. METHODS: The PubMed, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched up to August 2022 to identify randomized controlled trials on the effects of physical exercise interventions on balance, postural stability, and general mobility. The network meta-analysis included pairwise and indirect comparisons of results on the ABC scale, BBS, MiniBESTest, and TUG across 8 categories of physical exercise. RESULTS: Eighty-six studies with a total of 4,693 patients were included. For the ABC scale, the indirect comparison showed that the highest effect size was observed for balance vs sensorimotor training without including endurance interventions (0.62; 95% confidence interval (95% CI) 0.06, 1.17). The highest effect sizes for BBS were observed for alternative exercises (1.21; 95% CI 0.62, 1.81), body-weight supported (BWS) interventions (1.31; 95% CI 0.57, 2.05), dance (1.18; 95% CI 0.33, 2.03) and sensorimotor training, including endurance interventions (1.10; 95% CI 0.46, 1.75) vs control groups. Indirect comparisons showed that the highest effect size for the MiniBESTest were observed for balance (0.75; 95% CI 0.46, 1.04) and resistance (0.58; 95% CI 0.10, 1.07) vs control groups. For the TUG, comparisons showed a significant effect size for alternative exercises (-0.54; 95% CI -0.82, -0.26), balance (-0.42; 95% CI -0.75, -0.08), resistance (-0.60; 95% CI -0.89, -0.31), and sensorimotor training including endurance interventions (-0.61; 95% CI -0.95, -0.27) vs control comparisons. CONCLUSION: Balance interventions improve balance, postural stability, and general mobility in people with Parkinson's disease. Moreover, alternative exercises, dance, BWS interventions, resistance, and sensorimotor training, including and not including endurance interventions, are also effective.

The association between vitamin-D deficiency and fecal incontinence.

BACKGROUND: Vitamin-D is essential for musculoskeletal health. We aimed to determine whether patients with fecal incontinence (FI): (1) are more likely to have vitamin-D deficiency and, (2) have higher rates of comorbid medical conditions. METHODS: We examined 18- to 90-year-old subjects who had 25-hydroxy vitamin-D levels, and no vitamin-D supplementation within 3 months of testing, in a large, single-institutional electronic health records dataset, between 2017 and 2022. Cox proportional hazards survival analysis was used to assess association of vitamin-D deficiency on FI. KEY RESULTS: Of 100,111 unique individuals tested for serum 25-hydroxy vitamin-D, 1205 (1.2%) had an established diagnosis of FI. Most patients with FI were female (75.9% vs. 68.7%, p = 0.0255), Caucasian (66.3% vs. 52%, p = 0.0001), and older (64.2 vs. 53.8, p < 0.0001). Smoking (6.56% vs. 2.64%, p = 0.0001) and GI comorbidities, including constipation (44.9% vs. 9.17%, p = 0.0001), irritable bowel syndrome (20.91% vs. 3.72%, p = 0.0001), and diarrhea (28.55% vs. 5.2%, p = 0.0001) were more common among FI patients. Charlson Comorbidity Index score was significantly higher in patients with FI (5.5 vs. 2.7, p < 0.0001). Significantly higher proportions of patients with FI had vitamin-D deficiency (7.14% vs. 4.45%, p < 0.0001). Moreover, after propensity-score matching, rate of new FI diagnosis was higher in patients with vitamin-D deficiency; HR 1.9 (95% CI [1.14-3.15]), p = 0.0131. CONCLUSION & INFERENCES: Patients with FI had higher rates of vitamin-D deficiency along with increased overall morbidity. Future research is needed to determine whether increased rate of FI in patients with vitamin-D deficiency is related to frailty associated with increased medical morbidities.

Cross-country analysis of contextual factors and implementation strategies in under-5 mortality reduction in six low- and middle-income countries 2000-2015.

BACKGROUND: The Exemplars in Under-5 Mortality (U5M) was a multiple cases study of how six low- and middle-income countries (LMICs), Bangladesh, Ethiopia, Nepal, Peru, Rwanda, and Senegal, implemented health system-delivered evidence-based interventions (EBIs) to reduce U5M between 2000 and 2015 more effectively than others in their regions or with similar economic growth. Using implementation research, we conducted a cross-country analysis to compare decision-making pathways for how these countries chose, implemented, and adapted strategies for health system-delivered EBIs that mitigated or leveraged contextual factors to improve implementation outcomes in reducing amenable U5M. METHODS: The cross-country analysis was based on the hybrid mixed methods implementation research framework used to inform the country case studies. The framework included a common pathway of Exploration, Preparation, Implementation, Adaptation, and Sustainment (EPIAS). From the existing case studies, we extracted contextual factors which were barriers, facilitators, or determinants of strategic decisions; strategies to implement EBIs; and implementation outcomes including acceptability and coverage. We identified common factors and strategies shared by countries, and individual approaches used by countries reflecting differences in contextual factors and goals. RESULTS: We found the six countries implemented many of the same EBIs, often using similar strategies with adaptations to local context and disease burden. Common implementation strategies included use of data by decision-makers to identify problems and prioritize EBIs, determine implementation strategies and their adaptation, and measure outcomes; leveraging existing primary healthcare systems; and community and stakeholder engagement. We also found common facilitators included culture of donor and partner coordination and culture and capacity of data use, while common barriers included geography and culture and beliefs. We found evidence for achieving implementation outcomes in many countries and EBIs including acceptability, coverage, equity, and sustainability. DISCUSSION: We found all six countries used a common pathway to implementation with a number of strategies common across EBIs and countries which contributed to progress, either despite contextual barriers or by leveraging facilitators. The transferable knowledge from this cross-country study can be used by other countries to more effectively implement EBIs known to reduce amenable U5M and contribute to strengthening health system delivery now and in the future.

Inequity in the face of success: understanding geographic and wealth-based equity in success of facility-based delivery for under-5 mortality reduction in six countries.

BACKGROUND: Between 2000-2015, many low- and middle-income countries (LMICs) implemented evidence-based interventions (EBIs) known to reduce under-5 mortality (U5M). Even among LMICs successful in reducing U5M, this drop was unequal subnationally, with varying success in EBI implementation. Building on mixed methods multi-case studies of six LMICs (Bangladesh, Ethiopia, Nepal, Peru, Rwanda, and Senegal) leading in U5M reduction, we describe geographic and wealth-based equity in facility-based delivery (FBD), a critical EBI to reduce neonatal mortality which requires a trusted and functional health system, and compare the implementation strategies and contextual factors which influenced success or challenges within and across the countries. METHODS: To obtain equity gaps in FBD coverage and changes in absolute geographic and wealth-based equity between 2000-2015, we calculated the difference between the highest and lowest FBD coverage across subnational regions and in the FBD coverage between the richest and poorest wealth quintiles. We extracted and compared contextual factors and implementation strategies associated with reduced or remaining inequities from the country case studies. RESULTS: The absolute geographic and wealth-based equity gaps decreased in three countries, with greatest drops in Rwanda - decreasing from 50 to 5% across subnational regions and from 43 to 13% across wealth quintiles. The largest increases were seen in Bangladesh - from 10 to 32% across geography - and in Ethiopia - from 22 to 58% across wealth quintiles. Facilitators to reducing equity gaps across the six countries included leadership commitment and culture of data use; in some countries, community or maternal and child health insurance was also an important factor (Rwanda and Peru). Barriers across all the countries included geography, while country-specific barriers included low female empowerment subnationally (Bangladesh) and cultural beliefs (Ethiopia). Successful strategies included building on community health worker (CHW) programs, with country-specific adaptation of pre-existing CHW programs (Rwanda, Ethiopia, and Senegal) and cultural adaptation of delivery protocols (Peru). Reducing delivery costs was successful in Senegal, and partially successful in Nepal and Ethiopia. CONCLUSION: Variable success in reducing inequity in FBD coverage among countries successful in reducing U5M underscores the importance of measuring not just coverage but also equity. Learning from FBD interventions shows the need to prioritize equity in access and uptake of EBIs for the poor and in remote areas by adapting the strategies to local context.