Fine-scale maps of malaria incidence to inform risk stratification in Laos.

BACKGROUND: Malaria risk maps are crucial for controlling and eliminating malaria by identifying areas of varying transmission risk. In the Greater Mekong Subregion, these maps guide interventions and resource allocation. This article focuses on analysing changes in malaria transmission and developing fine-scale risk maps using five years of routine surveillance data in Laos (2017-2021). The study employed data from 1160 geolocated health facilities in Laos, along with high-resolution environmental data. METHODS: A Bayesian geostatistical framework incorporating population data and treatment-seeking propensity was developed. The models incorporated static and dynamic factors and accounted for spatial heterogeneity. RESULTS: Results showed a significant decline in malaria cases in Laos over the five-year period and a shift in transmission patterns. While the north became malaria-free, the south experienced ongoing transmission with sporadic outbreaks. CONCLUSION: The risk maps provided insights into changing transmission patterns and supported risk stratification. These risk maps are valuable tools for malaria control in Laos, aiding resource allocation, identifying intervention gaps, and raising public awareness. The study enhances understanding of malaria transmission dynamics and facilitates evidence-based decision-making for targeted interventions in high-risk areas.

Single-cell RNA-sequencing of human eosinophils in allergic inflammation in the esophagus.

BACKGROUND: Eosinophils are elusive cells involved in allergic inflammation. Single-cell RNA-sequencing (scRNA-seq) is an emerging approach to deeply characterize cellular properties, heterogeneity, and functionality. OBJECTIVES: We sought to comprehensively characterize the transcriptome and biological functions of human eosinophils at a site of severe allergic inflammation in the esophagus (ie, eosinophilic esophagitis [EoE]). METHODS: We employed a gravity-based scRNA-seq methodology to sequence blood eosinophils from patients with EoE and control individuals compared to a reanalyzed public scRNA-seq dataset of human esophageal eosinophils of EoE patients. We used flow cytometry, immunostaining, and a stimulation assay to verify mRNA findings. RESULTS: In total, scRNA-seq was obtained from 586 eosinophils (188 from blood [n = 6 individuals] and 398 from esophagus [n = 6 individuals]). The esophageal eosinophils were composed of a population of activated eosinophils (enriched in 659 genes compared with peripheral blood-associated eosinophils) and a small population of eosinophils resembling peripheral blood eosinophils (enriched in 62 genes compared with esophageal eosinophils). Esophageal eosinophils expressed genes involved in sensing and responding to diverse stimuli, most notably IFN-γ, IL-10, histamine and leukotrienes, and succinate. Esophageal eosinophils were most distinguished from other esophageal populations by gene expression of the receptors CCR3, HRH4, SUCNR1, and VSTM1; transcription factors CEBPE, OLIG1, and OLIG2; protease PRSS33; and the hallmark eosinophil gene CLC. A web of bidirectional eosinophil interactions with other esophageal populations was derived. Comparing esophageal eosinophils and mast cells revealed that esophageal eosinophils expressed genes involved in DNAX-activation protein-12 (also known as TYROBP) interactions, IgG receptor-triggered events, immunoregulation, and IL-10 signaling. CONCLUSIONS: In EoE, esophageal eosinophils exist as 2 populations, a minority population resembling blood eosinophils and the other population characterized by high de novo transcription of diverse sensing receptors and inflammatory mediators readying them to potentially intersect with diverse cell types.

Weight reduction and the impact on apnea-hypopnea index: A systematic meta-analysis.

Obstructive sleep apnea (OSA) is strongly associated with obesity. While the relationship between weight reduction and apnea-hypopnea index improvement has been documented, to our knowledge, it has not been quantified adequately. Therefore, this study aimed to quantify the relationship between weight reduction and AHI change. METHODS: A systematic literature search was performed using meta-analyses (PRISMA) guidelines for studies reporting AHI and weight loss in people with obesity/overweight and OSA between 2000 and 2023. A linear and quadratic model (weighted by treatment arm sample size) predicted percent change from baseline AHI against mean percent change from baseline weight. The quadratic term was statistically significant (P < 0.05), so the quadratic model (with 95 % prediction interval) was used. RESULTS: The literature search identified 27 studies/32 treatment arms: 15 using bariatric surgery and lifestyle intervention each and 2 using pharmacological interventions. Included studies were ≥3 months with weight intervention and participants had AHI ≥15/h. Weight reduction in people with OSA and obesity was associated with improvements in the severity of OSA. BMI reduction of 20 % was associated with AHI reduction of 57 %, while further weight reduction beyond 20 % in BMI was associated with a smaller effect on AHI. As the prediction intervals are relatively wide, a precise relationship could not be conclusively established. CONCLUSION: The degree of AHI index improvement was associated with the magnitude of weight reduction. The model suggests that with progress in weight reduction beyond 20 %, the incremental decrease in BMI appeared to translate to a smaller additional effect on AHI.

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

BACKGROUND: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment. METHODS: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure. RESULTS: At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was -25.3 events per hour (95% confidence interval [CI], -29.3 to -21.2) with tirzepatide and -5.3 events per hour (95% CI, -9.4 to -1.1) with placebo, for an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was -29.3 events per hour (95% CI, -33.2 to -25.4) with tirzepatide and -5.5 events per hour (95% CI, -9.9 to -1.2) with placebo, for an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity. CONCLUSIONS: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).

Weight-Reduction Preferences Among OBSERVE Study Participants With Obesity or Overweight: Opportunities for Shared Decision-Making.

OBJECTIVE: Limited recent evidence exists regarding weight-reduction preferences among people with obesity in the United States (US). We assessed preferred magnitudes of weight reduction among adults with obesity and how these preferences differ by participant characteristics. METHODS: The Perceptions, Barriers, and Opportunities for Anti-obesity Medications in Obesity Care: A Survey of Patients, Providers and Employers was a cross-sectional study assessing perceptions of obesity and anti-obesity medications among people with obesity, healthcare providers, and employers in the US. Adults with obesity and overweight with obesity-related complications self-reported current weight and weight they associated with 5 preferences ("dream," "goal," "happy," "acceptable," and "disappointed.") Preferred percent weight reductions for each preference were calculated. Multivariable regression analyses were performed identifying associations between weight-reduction preferences and participant characteristics. RESULTS: The study included 1007 participants (women: 63.6%; White: 41.0%; Black or African American: 28.9%; Asian: 6.5%; Hispanic: 15.3%; and median body mass index (BMI): 34.2 kg/m2). Median preferred percent weight reductions were dream = 23.5%; goal = 16.7%; happy = 14.6%; acceptable = 10.3%; and disappointed = 4.8%. Women reported higher preferred weight reductions than men. Preferred weight reductions among Black/African American participants were lower than White participants. Regression analyses indicated significant associations, with higher preferred magnitudes of weight reduction within females, higher weight self-stigma, and BMI class in Hispanic participants compared to White. CONCLUSION: In this large, real-world study, preferred magnitudes of weight reduction exceeded outcomes typically achieved with established nonsurgical obesity treatments but may be attained with bariatric procedures and newer and emerging anti-obesity medications. Respecting patients' preferences for treatment goals with obesity management could help support shared decision-making. Evaluating for an individual's contributors to weight preferences, such as weight self-stigma, can further benefit holistic obesity care.

Eosinophil Specialization Is Regulated by Exposure to the Esophageal Epithelial Microenvironment.

Distinct subsets of eosinophils are reported in inflammatory and healthy tissues, yet the functions of uniquely specialized eosinophils and the signals that elicit them, particularly in eosinophilic esophagitis (EoE), are not well understood. Herein, we report an ex-vivo system wherein freshly isolated human eosinophils were cocultured with esophageal epithelial cells and disease-relevant pro-inflammatory (IL-13) or pro-fibrotic (TGF-ß) cytokines. Compared with untreated cocultures, IL-13 increased expression of CD69 on eosinophils, whereas TGF-ß increased expression of CD81, CD62L, and CD25. Eosinophils from IL-13-treated cocultures demonstrated increased secretion of GRO-α, IL-8, and M-CSF and also generated increased extracellular peroxidase activity following activation. Eosinophils from TGF-ß-treated cocultures secreted increased IL-6 and exhibited increased chemotactic response to CCL11 compared with eosinophils from untreated or IL-13-treated coculture conditions. When eosinophils from TGF-ß-treated cocultures were cultured with fibroblasts, they upregulated SERPINE1 expression and fibronectin secretion by fibroblasts compared with eosinophils that were cultured with GM-CSF, alone. Translational studies revealed that CD62L was heterogeneously expressed by eosinophils in patient biopsies. Our results demonstrate that disease-relevant pro-inflammatory and pro-fibrotic signals present in the esophagus of EoE patients cause distinct profiles of eosinophil activation and gene expression.

Asynchronous Versus Synchronous Screening for Depression and Suicidality in a Primary Health Care System: Quality Improvement Study.

Background: Despite being a debilitating, costly, and potentially life-threatening condition, depression is often underdiagnosed and undertreated. Previsit Patient Health Questionnaire-9 (PHQ-9) may help primary care health systems identify symptoms of severe depression and prevent suicide through early intervention. Little is known about the impact of previsit web-based PHQ-9 on patient care and safety. Objective: We aimed to investigate differences among patient characteristics and provider clinical responses for patients who complete a web-based (asynchronous) versus in-clinic (synchronous) PHQ-9. Methods: This quality improvement study was conducted at 33 clinic sites across 2 health systems in Northern California from November 1, 2020, to May 31, 2021, and evaluated 1683 (0.9% of total PHQs completed) records of patients endorsing thoughts that they would be better off dead or of self-harm (question 9 in the PHQ-9) following the implementation of a depression screening program that included automated electronic previsit PHQ-9 distribution. Patient demographics and providers' clinical response (suicide risk assessment, triage nurse connection, medication management, electronic consultation with psychiatrist, and referral to social worker or psychiatrist) were compared for patients with asynchronous versus synchronous PHQ-9 completion. Results: Of the 1683 patients (female: n=1071, 63.7%; non-Hispanic: n=1293, 76.8%; White: n=831, 49.4%), Hispanic and Latino patients were 40% less likely to complete a PHQ-9 asynchronously (odds ratio [OR] 0.6, 95% CI 0.45-0.8; P<.001). Patients with Medicare insurance were 36% (OR 0.64, 95% CI 0.51-0.79) less likely to complete a PHQ-9 asynchronously than patients with private insurance. Those with moderate to severe depression were 1.61 times more likely (95% CI 1.21-2.15; P=.001) to complete a PHQ-9 asynchronously than those with no or mild symptoms. Patients who completed a PHQ-9 asynchronously were twice as likely to complete a Columbia-Suicide Severity Rating Scale (OR 2.41, 95% CI 1.89-3.06; P<.001) and 77% less likely to receive a referral to psychiatry (OR 0.23, 95% CI 0.16-0.34; P<.001). Those who endorsed question 9 "more than half the days" (OR 1.62, 95% CI 1.06-2.48) and "nearly every day" (OR 2.38, 95% CI 1.38-4.12) were more likely to receive a referral to psychiatry than those who endorsed question 9 "several days" (P=.002). Conclusions: Shifting depression screening from in-clinic to previsit led to a dramatic increase in PHQ-9 completion without sacrificing patient safety. Asynchronous PHQ-9 can decrease workload on frontline clinical team members, increase patient self-reporting, and elicit more intentional clinical responses from providers. Observed disparities will inform future improvement efforts.

Transhumeral prosthesis use affects upper body kinematics and kinetics.

BACKGROUND: Transhumeral (TH) limb loss leads to loss of body mass and reduced shoulder range of motion. Despite most owning a prosthesis, prosthesis abandonment is common. The consequence of TH limb loss and prosthesis use and disuse during gait may be compensation in the upper body, contributing to back pain or injury. Understanding the impact of not wearing a TH prosthesis on upper body asymmetries and spatial-temporal aspects of gait will inform how TH prosthesis use and disuse affects the body. RESEARCH QUESTION: Does TH limb loss alter upper body asymmetries and spatial-temporal parameters during gait when wearing and not wearing a prosthesis compared to able-bodied controls? METHODS: Eight male TH limb loss participants and eight male control participants completed three gait trials at self-selected speeds. The TH limb loss group performed trials with and without their prosthesis. Arm swing, trunk angular displacement, trunk-pelvis moment, and spatial-temporal aspects were compared using non-parametric statistical analyses. RESULTS: Both TH walking conditions showed greater arm swing in the intact limb compared to the residual (p≤0.001), resulting in increased asymmetry compared to the control group (p≤0.001). Without the prosthesis, there was less trunk flexion and lateral flexion compared to the control group (p≤0.001). Maximum moments between the trunk and pelvis were higher in the TH group than the control group (p≤0.05). Spatial-temporal parameters of gait did not differ between the control group and either TH limb loss condition. SIGNIFICANCE: Prosthesis use affects upper body kinematics and kinetics, but does not significantly impact spatial-temporal aspects of gait, suggesting these are compensatory actions. Wearing a prosthesis helps achieve more normative upper body kinematics and kinetics than not wearing a prosthesis, which may help limit back pain. These findings emphasize the importance of encouraging at least passive use of prostheses for individuals with TH limb loss.

Pathophysiology of Non-Esophageal Eosinophilic Gastrointestinal Disorders.

Eosinophilic gastrointestinal disorder (EGID) is an umbrella term encompassing a group of chronic, immune-mediated disorders characterized by eosinophil-rich inflammation affecting one or more segments of the gastrointestinal tract. A recent consensus in nomenclature and emerging data made possible through multi-center consortia are beginning to unravel the molecular and cellular underpinnings of EGIDs below the esophagus. These emerging findings are revealing both overarching commonalities related to a food allergen-driven, chronic, Th2-mediated immune response as well as location-specific nuances in the pathophysiology of the collective EGIDs. Altogether, these advances offer promise for improved diagnoses and more efficacious interventional strategies.

The effect of amplitude normalization technique, walking speed, and reporting metric on whole-body angular momentum and its interpretation during normal gait.

Whole-body angular momentum (WBAM) represents the cancellations of angular momenta that are produced during a reciprocal gait pattern. WBAM is sensitive to small changes and is used to compare dynamic gait patterns under different walking conditions. Study designs and the normalization techniques used to define WBAM vary and make comparisons between studies difficult. To address this problem, WBAM about each anatomical axis of rotation from a healthy control population during normal gait were investigated within four metrics: 1) range of WBAM, 2) integrated WBAM, 3) statistical parametric mapping (SPM), and 4) principal component analysis (PCA). These data were studied as a function of walking speed and normalization. Normalization techniques included: 1) no normalization, 2) normalization by height, body mass and walking speed, and 3) normalization by height, body mass and a scalar number, gravity×height, that is independent of walking velocity. Significant results were obtained as a function of walking speed regardless of normalization technique. However, the interpretation of significance within each metric was dependent on the normalization technique. Method 3 was the most robust technique as the differences were not altered from the expected relationships within the raw data. Method 2 actually inverted the expected relationship in WBAM amplitude as a function of walking speed, which skewed the results and their interpretation. Overall, SPM and PCA statistical methods provided better insights into differences that may be important. However, depending on the normalization technique used, caution is advised when interpreting significant findings when comparing participants with disparate walking speeds.

Extended physiological proprioception is affected by transhumeral Socket-Suspended prosthesis use.

The objective of this study was to define targeted reaching performance without visual information for transhumeral (TH) prosthesis users, establishing baseline information about extended physiological proprioception (EPP) in this population. Subjects completed a seated proprioceptive targeting task under simultaneous motion capture, using their prosthesis and intact limb. Eight male subjects, median age of 58 years (range 29-77 years), were selected from an ongoing screening study to participate. Five subjects had a left-side TH amputation, and three a right-side TH amputation. Median time since amputation was 9 years (range 3-54 years). Four subjects used a body-powered prosthetic hook, three a myoelectric hand, and one a myoelectric hook. The outcome measures were precision and accuracy, motion of the targeting hand, and joint angular displacement. Subjects demonstrated better precision when targeting with their intact limb compared to targeting with their prosthesis, 1.9 cm2 (0.8-3.0) v. 7.1 cm2 (1.3-12.8), respectively, p = 0.008. Subjects achieved a more direct reach path ratio when targeting with the intact limb compared to with the prosthesis, 1.2 (1.1-1.3) v. 1.3 (1.3-1.4), respectively, p = 0.039 The acceleration, deceleration, and corrective phase durations were consistent between conditions. Trunk angular displacement increased in flexion, lateral flexion, and axial rotation while shoulder flexion decreased when subjects targeted with their prosthesis compared to the intact limb. The differences in targeting precision, reach patio ratio, and joint angular displacements while completing the targeting task indicate diminished EPP. These findings establish baseline information about EPP in TH prosthesis users for comparison as novel prosthesis suspension systems become more available to be tested.

Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.

BACKGROUND: Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity. METHODS: SURMOUNT-OSA, a randomized, placebo -controlled, 52-week phase 3 trial, is investigating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA (apnea hypopnea- index ≥15 events/h) in participants with obesity (body mass index ≥30 kg/m2) and an established OSA diagnosis. SURMOUNT-OSA is made of 2 intervention-specific appendices (ISAs): ISA-1 includes participants with no current OSA treatment, and ISA-2 includes participants using positive airway pressure therapy. Overall, 469 participants have been randomized 1:1 to receive tirzepatide or placebo across the master protocol (ISA-1, n = 234; ISA-2, n = 235). All participants are also receiving lifestyle intervention for weight reduction. RESULTS: The primary endpoint for the individual ISAs is the difference in apnea hypopnea- index response, as measured by polysomnography, between tirzepatide and placebo arms at week 52. Secondary endpoints include sleep apnea-specific hypoxic burden, functional outcomes, and cardiometabolic biomarkers. The trial employs digital wearables, including home sleep testing to capture time to improvement and accelerometry for daily physical activity assessment, to evaluate exploratory outcomes. CONCLUSION: SURMOUNT-OSA brings a novel design to investigate if tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting the underlying etiology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05412004.

Malaria risk stratification in Lao PDR guides program planning in an elimination setting.

Malaria in Lao People's Democratic Republic (Lao PDR) has declined rapidly over the last two decades, from 279,903 to 3926 (99%) cases between 2001 and 2021. Elimination of human malaria is an achievable goal and limited resources need to be targeted at remaining hotspots of transmission. In 2022, the Center of Malariology, Parasitology and Entomology (CMPE) conducted an epidemiological stratification exercise to assign districts and health facility catchment areas (HFCAs) in Lao PDR based on malaria risk. The stratification used reported malaria case numbers from 2019 to 2021, risk maps derived from predictive modelling, and feedback from malaria staff nationwide. Of 148 districts, 14 were deemed as burden reduction (high risk) districts and the remaining 134 as elimination (low risk) districts. Out of 1235 HFCAs, 88 (7%) were classified as highest risk, an improvement from 187 (15%) in the last stratification in 2019. Using the HFCA-level stratification, the updated stratification resulted in the at-risk population (total population in Strata 2, 3 and 4 HFCAs) declining from 3,210,191 to 2,366,068, a 26% decrease. CMPE are using the stratification results to strengthen targeting of resources. Updating national stratifications is a necessary exercise to assess progress in malaria control, reassign interventions to the highest risk populations in the country and ensure greatest impact of limited resources.

Prevalence of maternal depression and anxiety symptoms and associations with child mental health outcomes in rural Nepal.

OBJECTIVES: This study describes the prevalence, associated factors and child mental health outcomes related to symptoms of maternal depression and anxiety within 5 years after childbirth in a rural district in Nepal. This association is not well-understood in rural, community-based settings in low- and middle-income countries (LMIC). METHODS: A sample of 347 women with children under 5 years was recruited in September 2019 for a cross-sectional study in the rural Saptari district in Nepal. Multivariable logistic regression was used to investigate the association between maternal depressive or anxiety symptoms and children's experience and impact of emotional and behavioural difficulties. RESULTS: In total, 144 women (41.5%) had moderate or severe depression symptoms and 118 (34%) had anxiety symptoms. Mothers with a lower income were more likely to have anxiety symptoms than the highest income group (OR: 1.8, 95% CI: 1.1-3.0). An association existed between maternal depressive symptoms and the impact of emotional or behavioural difficulties in children (OR: 2.44, 95% CI: 1.02-5.84). In contrast, there was no association between maternal anxiety and child outcomes. CONCLUSIONS: Our findings suggest that the prevalence of probable maternal anxiety and depression symptoms was relatively high in this rural, low-resourced and community-based setting in Nepal. Maternal depressive symptoms were associated with the degree of impact on children's mental health post-infancy, emphasising the importance of improving maternal mental health in the early years of a child's life.

Weight management treatment modalities in patients with overweight or obesity: A retrospective cohort study of administrative claims data.

Background: The purpose of this study was to describe demographic and clinical characteristics among patients who have medical encounters for weight management treatments and to investigate the association of those characteristics with treatment modality. Methods: This was a retrospective database study using medical claims, pharmacy claims, and enrollment information from commercial and Medicare Advantage with Part D members in the Optum Research Database from 01/01/2011-2/29/2020. Adult patients with a claim for a weight management treatment from 01/01/2012-2/28/2019 were categorized into cohorts according to the highest intensity intervention received. To examine the association between patient characteristics and treatment modality received, a multinomial logit model was performed. Results: Cohorts by increasing intensity included lifestyle intervention (LSI, n = 67,679), weight reduction pharmacotherapy (WRRx) with an anti-obesity medication (AOM, n = 6,905), weight reduction procedure (WRP, n = 1,172), and weight reduction surgery (WRS, n = 18,036). Approximately 32.1% and 16.6% of patients who received WRS or WRP had an LSI during the 12-month baseline, and only 0.6% and 0.4% had treatment with long-term AOMs. In a multinomial logit model, patients with type 2 diabetes (not including WRRx cohort), respiratory disorders, cardiovascular risk factors, pain disorders, and mental health conditions had increased odds of treatment with higher intensity intervention versus LSI. Patients who were male, received an intervention more recently (2016-2019), or had a Charlson comorbidity score of 1 (compared to 0) had decreased odds of treatment with higher intensity interventions. Conclusion: In this study, age, sex, body mass index, obesity-related complications, and Charlson comorbidity score appeared to influence the type of weight management treatment modality received. This study improves understanding of weight management treatment utilization and identifies gaps and opportunities to improve obesity care with the appropriate use of different treatment modalities.

Baseline soil-transmitted helminth and schistosome infection in the Geshiyaro project, Ethiopia: A unique transmission interruption project using biometric fingerprinting for longitudinal individual analysis.

BACKGROUND: The Geshiyaro project aims to assess the feasibility of interrupting transmission of soil-transmitted helminths (STH) and schistosome (SCH) infection in the Wolaita zone of southern Ethiopia through high coverage community-wide mass drug administration (MDA), in combination with improved water, sanitation, and hygiene services and behaviour change communication delivered through the existing health care infrastructure. To accurately measure treatment coverage a population census was conducted enrolling individuals with biometric fingerprinting and barcoded ID cards. This paper details the baseline census and parasitology surveys conducted before the start of any interventions. METHODS: The census was conducted in five of the 15 Wolaita districts between October 2018 and December 2019, enrolling all consenting participants from every household. Simultaneously, a cross-sectional parasitology survey was conducted in 130 out of 361 randomly selected communities from all 15 districts, with 100 individuals across all age groups (infant to adult) per community providing stool and urine for analysis by duplicate Kato-Katz and a point-of-care circulating cathodic antigen (POC-CCA) to test for Schistosoma mansoni and STH, and microhaematuria and urine filtration for Schistosoma haematobium. Of the 130 communities, 30 were randomly selected for annual, longitudinal parasitological monitoring, with 150 randomly selected individuals from infant to adult providing two days of stool and urine samples for analysis by the same diagnostic tests per community. RESULTS: In total 97,919 households participated in the baseline census enrolling 466,071 individuals, with parasitological data obtained from 10,785 people. At baseline, 15.5% were infected with at least one STH species, with Ascaris lumbricoides (9.5%), followed by hookworm (7.2%) and Trichuris trichiura (1.8%). Substantial heterogeneity in STH prevalence was observed between communities ranging from 0% to 61% where most infections were low intensity. Schistosoma mansoni infection was the dominant schistosome infection (0.85% by Kato-Katz and 13.3% by POC-CCA trace negative and 21.5% trace positive), with few Schistosoma haematobium infections identified (2.77% haematuria positive and 0.13% positive by urine filtration). CONCLUSIONS: While the national control program in Ethiopia has made good progress in reducing prevalence of STH and SCH in Wolaita since it was launched in 2015, there remain areas of persistent infection suggesting the existence of environmental or behavioural risk factors that contribute to ongoing transmission. This project aims to identify the most efficient intervention strategies to reduce community burden and reach interruption of transmission.

The Association Between Depression and Substance Use Among Primary Care Patients With Comorbid Medical and Behavioral Health Conditions.

INTRODUCTION: The scope of primary care increasingly encompasses patient behavioral health problems, manifest typically through depression screening and treatment. Although substance use is highly comorbid with depression, it is not commonly identified and addressed in the primary care context. This study aimed to examine the association between the likelihood of substance use disorder and increased depression severity, both cross-sectionally and longitudinally, among a sample of 2409 patients from 41 geographically dispersed and diverse primary care clinics across the US. METHODS: This is secondary analysis of data obtained from a multi-site parent study of integrated behavioral health in primary care, among patients with both chronic medical and behavioral health conditions. Patient reported outcome surveys were gathered from patients at 3 time points. The primary care practices were blind to which of their patients completed surveys. Included were standardized measures of depression severity (Patient Health Questionnaire-9) [PHQ-9] and substance use disorder likelihood (Global Appraisal of Individual Needs-Short Screener [GSS]). RESULTS: Four percent of the study population screened positive for substance use disorder. PHQ-9 scores indicated depression among 43% of all patients. There was a significant association between the likelihood of substance use disorder and depression initially, at a 9-month follow-up, and over time. These associations remained significant after adjusting for age, gender, race, ethnicity, education, income, and other patient and contextual characteristics. CONCLUSIONS: The findings suggest that substance use disorder is associated with depression severity cross-sectionally and over time. Primary care clinics and health systems might consider implementing substance use screening in addition to the more common screening strategies for depression. Especially for patients with severe depression or those who do not respond to frontline depression treatments, the undermining presence of a substance use disorder should be explored.

Real-world primary nonadherence to antiobesity medications.

BACKGROUND: Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal treatment of patients with overweight and obesity who are newly prescribed antiobesity medications (AOMs). OBJECTIVES: To assess PNA among patients with newly prescribed AOMs and to examine factors associated with PNA to AOMs. METHODS: This was a retrospective study that used the Optum Integrated Clinical plus Claims database to identify individuals who had at least 1 prescription order for an AOM the US Food and Drug Administration approved for long-term use. Individuals with prescription orders between January 1, 2012, and February 28, 2019, were identified, and patient demographics, clinical characteristics, medication prescribed, baseline health care utilization, and obesity-related complications were described by PNA status. PNA was defined as no pharmacy claim for the AOM within 60 days of the date of the new prescription order as identified in electronic health record data. A multivariable logistic regression model was used to examine factors associated with PNA. RESULTS: The study sample included a total of 1,563 patients. The mean body mass index was 38.4 kg/m2; 10.7% were prescribed liraglutide 3.0 mg, 26.0% were prescribed lorcaserin, 36.3% of patients were prescribed naltrexone-bupropion, 5.4% were prescribed orlistat, and 21.6% were prescribed phentermine-topiramate. Most patients (91.1%) exhibited PNA, with only 8.9% filling their newly prescribed AOM within 60 days. Both the adherent and nonadherent groups were predominately female sex, White, and covered by commercial insurance. The mean age was similar between the 2 groups. Most obesity-related complications were less prevalent in the adherent group, although the Charlson comorbidity index score was similar between the 2 groups. After adjustment for patient demographics and clinical characteristics, there was not a statistically significant association between the specific AOM and PNA (P = 0.299). Patients with depression or living in the Midwest or South regions were at significantly increased risk of PNA. CONCLUSIONS: The rate of PNA to AOMs was very high, suggesting barriers in effective medical management of patients with overweight and obesity. Future research is warranted to understand reasons for PNA to AOMs and how to address these barriers. DISCLOSURES: Dr Kan, Dr Bae, Dr Dunn, and Dr Ahmad are employees of Eli Lilly and Company. Ms Buysman and Dr Gronroos are employees of Optum. Dr Swindle was an employee of Optum at the time the study was conducted and is currently employed at Evidera. Dr Bengtson is employed at Boehringer Ingelheim Pharmaceuticals, Inc. (Boehringer Ingelheim has no connection to this study), and during the conduct of this study was employed at Optum.

Dorsal striatal response to taste is modified by obesity and insulin resistance.

OBJECTIVE: In preclinical models, insulin resistance in the dorsal striatum (DS) contributes to overeating. Although human studies support the concept of central insulin resistance, they have not investigated its effect on consummatory reward-induced brain activity. METHODS: Taste-induced activation was assessed in the caudate and putamen of the DS with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Three phenotypically distinct groups were studied: metabolically healthy lean, metabolically healthy obesity, and metabolically unhealthy obesity (MUO; presumed to have central insulin resistance). Participants with MUO also completed a weight loss intervention followed by a second functional magnetic resonance imaging session. RESULTS: The three groups were significantly different at baseline consistent with the design. The metabolically healthy lean group had a primarily positive BOLD response, the MUO group had a primarily negative BOLD response, and the metabolically healthy obesity group had a response in between the two other groups. Food craving was predicted by taste-induced activation. After weight loss in the MUO group, taste-induced activation increased in the DS. CONCLUSIONS: These data support the hypothesis that insulin resistance and obesity contribute to aberrant responses to taste in the DS, which is only partially attenuated by weight loss. Aberrant responses to food exposure may be a barrier to weight loss.

Tirzepatide Reduces Appetite, Energy Intake, and Fat Mass in People With Type 2 Diabetes.

OBJECTIVE: To evaluate the effects of tirzepatide on body composition, appetite, and energy intake to address the potential mechanisms involved in body weight loss with tirzepatide. RESEARCH DESIGN AND METHODS: In a secondary analysis of a randomized, double-blind, parallel-arm study, the effects of tirzepatide 15 mg (N = 45), semaglutide 1 mg (N = 44), and placebo (N = 28) on body weight and composition, appetite, and energy intake were assessed at baseline and week 28. RESULTS: Tirzepatide treatment demonstrated significant reductions in body weight compared with placebo and semaglutide, resulting in greater fat mass reduction. Tirzepatide and semaglutide significantly reduced appetite versus placebo. Appetite scores and energy intake reductions did not differ between tirzepatide and semaglutide. CONCLUSIONS: Differences in energy intake during ad libitum lunch were not sufficient to explain the different weight outcomes. Further evaluation is needed to assess mechanistic differences related to tirzepatide actions on 24-h energy intake, substrate utilization, and energy expenditure.