Higher ultra-processed food intake is associated with an increased incidence risk of cardiovascular disease: the Tehran lipid and glucose study.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of death worldwide, although limited data are currently available regarding the impact of consuming ultra-processed food (UPF) on its incidence. Given the increased consumption of UPF in Iran, we aimed to investigate the association between UPF intake and CVD risk. METHODS: Individuals without CVD (n = 2050) aged ≥ 30 years old were recruited from the Tehran Lipid and Glucose Study (TLGS). Dietary data were collected using a validated food frequency questionnaire (FFQ) and UPF intakes were assessed based on the Nova food classification. Multivariable Cox proportional hazard models adjusted for potential confounders were used to estimate the hazard ratio (HR) and 95% confidence intervals (95% CI) for the risk of CVD across tertiles of UPF intake. RESULTS: A 10.1% incidence of CVD occurred over a median follow-up of 10.6 years, with a 22% increase in CVD risk per each 50 g/day UPF intake. Participants with the highest intake of UPF had a 68% greater incidence of CVD compared to those with the lowest intake (HR = 1.68, 95% CI=1.14-2.48) after controlling for potential confounders. Regarding sub-groups of UPF, participants in the 3rd tertile compared to the reference had a significantly increased risk of CVD (HR = 1.56, 95% CI=1.04-2.34). Nevertheless, intake of bread, fast food, sweetened beverages, sweets and desserts, high-fat dairy products, and other UPFs were not associated with greater CVD risk. CONCLUSION: Our findings support the hypothesis that the incidence of CVD is enhanced with the higher consumption of UPF in a representative sample of the Iranian population.

The association of dietary carbohydrate quality and quantity with obesity among Iranian adolescents: a case-control study.

BACKGROUND: Adolescent obesity is considered as a major health concern worldwide which is closely linked to the quality of diet. The purpose of the present study was to assess the carbohydrate quality and quantity in relation to odds of overweight and obesity in adolescents. METHODS: This case-control study with a 1:1 ratio was conducted on 406 adolescents (14 to 18 years old) matched for age and gender. Participants were selected by multistage cluster random sampling method from March to October 2019 in Shiraz, Iran. Dietary intakes of the study population were assessed by a validated semi-quantitative food frequency questionnaire. Also anthropometric indices were measured using standard methods and demographic information was recorded via face to face interview. The relation between low carbohydrate diet score (LCDS) and carbohydrate quality index (CQI), and odds of obesity was evaluated by multiple Logistic regression. RESULTS: After adjusting the role of potential confounders, the participants in the third tertiles of LCDS (OR = 0.443, 95% CI = (0.260 to 0.755)) and CQI (OR = 0.005, 95% CI = (0.001 to 0.025)) had less odds of being overweight and obese compared to the first tertile. CONCLUSION: The present study found an inverse relationship between dietary quantity and quality of carbohydrate intake and the odds of overweight and obesity in a sample of Iranian adolescents.

Planning, implementing and governing systems-based co-creation: the DISCOVER framework.

BACKGROUND: Increasingly, public health faces challenges requiring complex, multifaceted and multi-sectoral responses. This calls for systems-based approaches that facilitate the kind of collective and collaborative thinking and working required to address complexity. While the literature on systems thinking, system dynamics and the associated methodologies is extensive, there remains little clear guidance on how to plan, govern and implement participatory systems approaches within a co-creation process. METHODS: We used a three-step process to develop DISCOVER, a framework for implementing, and governing systems-based co-creation: Stage 1: We conducted a literature analysis of key texts to identify well-documented methods and phases for co-creation using a systems approach, as well as areas where gaps existed. Stage 2: We looked for the most appropriate methods and approaches to fill the gaps in the knowledge production chain. Stage 3: We developed the framework, identifying how the different tools and approaches fit together end-to-end, from sampling and recruiting participants all the way through to responding with an action plan. RESULTS: We devised DISCOVER to help guide researchers and stakeholders to collectively respond to complex social, health and wider problems. DISCOVER is a strategic research planning and governance framework that provides an actionable, systematic way to conceptualise complex problems and move from evidence to action, using systems approaches and co-creation. In this article, we introduce the eight-step framework and provide an illustrative case study showcasing its potential. The framework integrates complementary approaches and methods from social network analysis, systems thinking and co-creation literature. The eight steps are followed sequentially but can overlap. CONCLUSIONS: DISCOVER increases rigour and transparency in system approaches to tackling complex issues going from planning to action. It is being piloted in environmental health research but may be suitable to address other complex challenges and could be incorporated into research proposals and protocols for future projects.

Correlation of miR-155-5p, KRAS, and CREB Expression in Patients with Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a type of blood cancer involving numerous aberrant genes and microRNAs. MiRNAs are non-coding sequences that have been proven to be players in the biological processes of various cancers. The present study is designed to illustrate the relationship between miR-155, KRAS, and CREB. METHODS: This case-control study was conducted on 21 patients with AML and 9 healthy individuals. The expressions of miR-155, KRAS, and CREB were measured using RT-PCR. Demographic data were extracted from the documents of individuals. SPSS and GraphPad Prism software were used to analyze the data. RESULTS: The expression of miR-155 in patients with AML was 35 times higher than in the control group (p < 0.0001). Also, CREB fold change increased by 1.92-fold in patients compared to the controls (p = 0.034), but no difference in KRAS was observed between the control and AML groups (p > 0.05). There was no change in miR-155, CREB, and KRAS expression based on gender, age, and blast percentage (p > 0.5). Nevertheless, there was a direct correlation between CREB and KRAS expressions (p = 0.0002). Our result showed that overexpression of CREB and KRAS would cause an increase in white blood cells (WBCs) (p = 0.001, 0.045 respectively), but there was no correlation between miR-155 with WBCs (p > 0.5). CONCLUSIONS: Our study revealed that miR-155 and CREB had overexpression compared to the control group.

Severity of adipose tissue dysfunction is associated with progression of pre-diabetes to type 2 diabetes: the Tehran Lipid and Glucose Study.

BACKGROUND: The association of prediabetes (Pre-DM) regression and progression with visceral adiposity index (VAI) and adipose tissue dysfunction (ATD) remains to be investigated. METHODS: The present cohort study was conducted within the framework of the Tehran Lipid and Glucose Study (TLGS) on 1458 Pre-DM cases (aged ≥ 21 years) who were followed for nine years. VAI was estimated based on waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol. ATD status (i.e., absent, mild-moderate, and severe) was defined based on the age-stratified cutoff values of VAI. Multinomial logistic regression models with adjustment of potential confounders were used to estimate the chance of Pre-DM regression to normoglycemia or progression to T2D across ATD status. RESULTS: During the study follow-up, 39.0% of the participants developed T2D, and 37.7% returned to normoglycemia. Compared to mild-moderate ATD, Pre-DM subjects with severe ATD had a higher risk of developing T2D by 45% (OR = 1.45, 95% CI = 11.08-1.93). Severe ATD was also associated with a decreased chance of returning to normoglycemia by 26% (OR = 0.74, 95% CI = 0.55-0.99). Participants with severe ATD had significantly higher fasting (overall mean = 111, 95% CI = 109-112 vs. 106, 95% CI = 105-108 mg/dL) and 2h-serum glucose (overall mean = 165, 95% CI = 161-168 vs. 153, 95% CI = 149-156 mg/dL) concentrations over time. CONCLUSION: Severe ATD was associated with an elevated risk of developing T2D and longitudinal poor-glycemic controls in Pre-DM subjects. ATD may be a simple and useful index for detecting subjects at a higher risk of Pre-DM progression to T2D, allowing for timely intervention strategies.

Unspoken Truths: Mental Health Among Academic Surgeons.

OBJECTIVE: To characterize the current state of mental health within the surgical workforce in the United States. BACKGROUND: Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. METHODS: Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. RESULTS: Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P <0.001), anxiety (31.6% vs. 16.2%, P =0.001), PTSD (12.8% vs. 5.6%, P =0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P =0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P =0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P <0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P =0.002) were associated with increased odds of suicidal ideation over the past 12 months. CONCLUSIONS: Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

Why Similar Policies Resulted In Different COVID-19 Outcomes: How Responsiveness And Culture Influenced Mortality Rates.

In the first two years of the COVID-19 pandemic, per capita mortality varied by more than a hundredfold across countries, despite most implementing similar nonpharmaceutical interventions. Factors such as policy stringency, gross domestic product, and age distribution explain only a small fraction of mortality variation. To address this puzzle, we built on a previously validated pandemic model in which perceived risk altered societal responses affecting SARS-CoV-2 transmission. Using data from more than 100 countries, we found that a key factor explaining heterogeneous death rates was not the policy responses themselves but rather variation in responsiveness. Responsiveness measures how sensitive communities are to evolving mortality risks and how readily they adopt nonpharmaceutical interventions in response, to curb transmission. We further found that responsiveness correlated with two cultural constructs across countries: uncertainty avoidance and power distance. Our findings show that more responsive adoption of similar policies saves many lives, with important implications for the design and implementation of responses to future outbreaks.

Grounding alcohol simulation models in empirical and theoretical alcohol research: a model for a Northern Plains population in the United States.

The growing number of systems science simulation models for alcohol use (AU) are often disconnected from AU models within empirical and theoretical alcohol research. As AU prevention/intervention efforts are typically grounded in alcohol research, this disconnect may reduce policy testing results, impact, and implementation. We developed a simulation model guided by AU research (accounting for the multiple AU stages defined by AU behavior and risk for harm and diverse transitions between stages). Simulated projections were compared to historical data to evaluate model accuracy and potential policy leverage points for prevention and intervention at risky drinking (RD) and alcohol use disorder (AUD) stages. Results indicated prevention provided the greatest RD and AUD reduction; however, focusing exclusively on AUD prevention may not be effective for long-term change, given the continued increase in RD. This study makes a case for the strength and importance of aligning subject-based research with systems science simulation models.

Solubility of mesalazine in pseudo-binary mixtures of choline chloride/ethylene glycol deep eutectic solvent and water at 293.15 K to 313.15 K.

Mesalazine (5-ASA) is a medication utilized to treat inflammatory bowel diseases involving ulcerative colitis and Crohn's disease. Mesalazine has fewer side effects but the low solubility and bioavailability of it is responsible for its delayed onset of action. Hence, the goal of this study is to determine the molar solubility of 5-ASA in aqueous pseudo-binary mixtures containing low toxic biocompatible choline chloride/ethylene glycol deep eutectic solvent (ChCl/EG DES) with DES mass fraction of 0.0-1.0 using a shake-flask technique at 293.2-313.2 K and approximately 85 kPa. The experimental results indicated that the solubility of 5-ASA enhanced by addition of DES mass fraction and also increasing temperature. The molarity values of 5-ASA were then modelled by some traditional cosolvency models, and regressed each model parameters. The back-computed molarity of 5-ASA using the selected cosolvency models presented a good consistency with the experimental data (lower mean percentage deviation than 5.14%). Moreover, the Gibbs and van't Hoff equations were employed to compute the thermodynamic functions of 5-ASA dissolution process in ChCl/EG DES + water from the temperature dependency of solubility data. This analysis presented an endothermic and entropy-driven process of 5-ASA dissolution in ChCl/EG DES + water. Furthermore, enthalpy-entropy compensation analysis represented non-linear enthalpy dissolution vs. Gibbs free energy compensation plots with positive and negative slopes for 5-ASA whereas the positive and negative slopes were probably due to the enhance in solvation of 5-ASA by ChCl/EG DES molecules and the solvent-structure loosing, respectively.

Factors Associated With Abrupt Discontinuation of Long-Term High-Dose Opioid Treatment.

This cohort study investigates factors associated with abrupt discontinuation of long-term high-dose opioid treatment at the national level and across US states.

How Funding Policy Maintains Structural Inequity Within Indigenous Community-Based Organizations.

Despite efforts to increase investment in Indigenous health and well-being in the United States, disparities remain. The way in which health-promoting organizations are funded is one key mechanism driving the systemic, long-term health disparities experienced by Indigenous people in the US. Using Indigenous-led community-based organizations (ICBOs) that provide psychosocial care as a case study, we highlight multiple ways in which policies that regulate the external funding that ICBOs depend on must change to promote equity and allow the organizations to flourish and address unmet psychosocial needs for Indigenous community members. We use a system dynamics approach to discuss how "capability traps" arise from a misfit between external funding regulations and organizations' needs for sustainability and effective care provision. We provide suggestions for reforming funding policies that focus on improving ICBO sustainability.

Understanding the dynamics emerging from the interplay among poor mental wellbeing, energy balance-related behaviors, and obesity prevalence in adolescents: A simulation-based study.

Both obesity and poor mental wellbeing have a high prevalence in European youth. Adolescents in six countries identified mental wellbeing factors as main drivers of youth obesity through systems mapping. This study sought to (1) explore the dynamics of the interplay between poor mental wellbeing, energy balance-related behaviors, and adolescent overweight and obesity prevalence and (2) test the effect of intervention point scenarios to reduce adolescent obesity. Drawing on the youth-generated systems maps and a literature synthesis, we built a simulation model that represents the links from major feedback pathways for poor mental wellbeing to changes in dietary, physical activity, and sleep behaviors. The model was calibrated using survey data from Norway, expert input, and literature and shows a good fit between simulated behavior and available statistical data. The simulations indicate that adolescent mental wellbeing is harmed by socio-cultural pressures and stressors, which trigger reinforcing feedback mechanisms related to emotional/binge eating, lack of motivation to engage in physical activity, and sleep difficulty. Targeting a combination of intervention points that support a 25% reduction of pressure on body image and psychosocial stress showed potentially favorable effects on mental wellbeing-doubling on average for boys and girls and decreasing obesity prevalence by over 4%.

Dynamics of colorectal cancer screening in low and middle-income countries: A modeling analysis from Thailand.

BACKGROUND: Low and middle-income countries face constraints for early colorectal cancer (CRC) detection, including restricted access to care and low colonoscopy capacity. Considering these constraints, we studied strategies for increasing access to early CRC detection and reducing CRC progression and mortality rates in Thailand. METHODS: We developed a system dynamics model to simulate CRC death and progression trends. We analyzed the impacts of increased access to screening via fecal immunochemical test and colonoscopy, improving access to CRC diagnosis among symptomatic individuals, and their combination. RESULTS: Projecting the status quo (2023-2032), deaths per 100K people increase from 87.5 to 115.4, and CRC progressions per 100K people rise from 131.8 to 159.8. In 2032, improved screening access prevents 2.5 CRC deaths and 2.5 progressions per 100K people, with cumulative prevented 7K deaths and 9K progressions, respectively. Improved symptom evaluation access prevents 7.5 CRC deaths per 100K with no effect on progression, totaling 35K saved lives. A combined approach prevents 9.3 deaths and 1.8 progressions per 100K, or 41K and 7K cumulatively. The combined strategy prevents most deaths; however, there is a tradeoff: It prevents fewer CRC progressions than screening access improvement. Increasing the current annual colonoscopy capacity (200K) to sufficient capacity (681K), the combined strategy achieves the best results, preventing 15.0 CRC deaths and 10.3 CRC progressions per 100K people, or 54K and 30K cumulatively. CONCLUSION: Until colonoscopy capacity increases, enhanced screening and symptom evaluation are needed simultaneously to curb CRC deaths, albeit not the best strategy for CRC progression prevention.

Long-Term Effects of Increasing Buprenorphine Treatment Seeking, Duration, and Capacity on Opioid Overdose Fatalities: A Model-based Analysis.

OBJECTIVES: Because buprenorphine treatment of opioid use disorder reduces opioid overdose deaths (OODs), expanding access to care is an important policy and clinical care goal. Policymakers must choose within capacity limitations whether to expand the number of people with opioid use disorder who are treated or extend duration for existing patients. This inherent tradeoff could be made less acute with expanded buprenorphine treatment capacity. METHODS: To inform such decisions, we used a validated simulation model to project the effects of increasing buprenorphine treatment-seeking, average episode duration, and capacity (patients per provider) on OODs in the United States from 2023 to 2033, varying the start time to assess the effects of implementation delays. RESULTS: Results show that increasing treatment duration alone could cost lives in the short term by reducing capacity for new admissions yet save more lives in the long term than accomplished by only increasing treatment seeking. Increasing provider capacity had negligible effects. The most effective 2-policy combination was increasing capacity and duration simultaneously, which would reduce OODs up to 18.6% over a decade. By 2033, the greatest reduction in OODs (≥20%) was achieved when capacity was doubled and average duration reached 2 years, but only if the policy changes started in 2023. Delaying even a year diminishes the benefits. Treatment-seeking increases were equally beneficial whether they began in 2023 or 2025 but of only marginal benefit beyond what capacity and duration achieved. CONCLUSIONS: If policymakers only target 2 policies to reduce OODs, they should be to increase capacity and duration, enacted quickly and aggressively.

The association between longitudinal trends in receipt of buprenorphine for opioid use disorder and buprenorphine-waivered providers in the United States.

AIMS, DESIGN AND SETTING: We sought to describe longitudinal trends in buprenorphine receipt and buprenorphine-waivered providers in the United States from 2003 to 2021 and measure whether the relationship between the two differed after capacity-building strategies were enacted nationally in 2017. This was a retrospective study of two separate cohorts covering the years 2003-21, testing whether the association between two trends in these cohorts changed comparing 2003 to 2016 and from 2017 to 2021, among buprenorphine providers in the United States, regardless of treatment setting. Patients receiving dispensed buprenorphine at retail pharmacies. PARTICIPANTS: All providers who have obtained a waiver to prescribe buprenorphine in the United States, and an estimate of the annual number of patients who had buprenorphine for opioid use disorder (OUD) dispensed to them at a retail pharmacy. MEASUREMENTS: We synthesized and summarized data from multiple sources to assess the cumulative number of buprenorphine-waivered providers over time. We used national-level prescription data from IQVIA to estimate annual buprenorphine receipt for OUD. FINDINGS: From 2003 to 2021, the number of buprenorphine-waivered providers in the United States increased from fewer than 5000 in the first 2 years of Food and Drug Administration (FDA) approval to more than 114 000 in 2021, while patients receiving buprenorphine products for OUD increased from approximately 19 000 to more than 1.4 million. The strength of association between waivered providers and patients is significantly different before and after 2017 (P < 0.001). From 2003 to 2016, for each additional provider, there was an average increase of 32.1 [95% confidence interval (CI) = 28.7-35.6] patients, but an increase of only 4.6 (95% CI= 3.5-5.7) patients for each additional provider, beginning in 2017. CONCLUSIONS: In the United States, the relationship between the rates of growth in buprenorphine providers and patients became weaker after 2017. While efforts to increase buprenorphine-waivered providers were successful, there was less success in translating that into significant increases in buprenorphine receipt.

Comparison of incisional, transverse abdominis plane, and rectus sheath blocks in dogs undergoing ovariohysterectomy.

OBJECTIVE: To compare the analgesia provided by incisional (Incisional), transverse abdominis plane (TAP), and rectus sheath (RS) blocks in dogs submitted for ovariohysterectomy (OHE). ANIMALS: 22 female mixed-breed dogs were allocated into 3 treatments of Incisional (n = 7), TAP (n = 7), and RS (n = 8) and underwent OHE from April 4 to December 6, 2022. PROCEDURES: After premedication with acepromazine (0.05 mg/kg) and morphine (0.5 mg/kg), anesthesia was induced (6 mg/kg) and maintained (0.4 mg/kg/min) with propofol. Each dog randomly received either an incisional (blind technique), TAP, or RS (ultrasound-guided) block. Intraoperative analgesia was assessed using cardiorespiratory variables. Postoperative analgesia was evaluated up to 6 hours after the operation with a Short Form of Glasgow Pain Scale (SF-GCPS) and Visual Analog Scale (VAS). Fentanyl was administered as a rescue analgesic when needed. RESULT: During surgery, all data remained within normal limits without any significant differences. Fentanyl was administered to 1 dog in the Incisional and 1 in the TAP. Post-operatively, a single dose of fentanyl was given to 1 dog in the TAP and 1 in the RS. Four dogs in the Incisional and 3 in the RS received both doses of fentanyl. There was no significant difference regarding postoperative rescue analgesia among treatments. CLINICAL RELEVANCE: All 3 techniques demonstrated acceptable intra- and post-operative analgesia efficacy in dogs undergoing OHE. Further studies are warranted to confirm these findings.

Electrosprayed Nanoparticles Containing Hydroalcoholic Extract of Echinacea purpurea (L.) Moench Stimulates Immune System by Increasing Inflammatory Factors in Male Wistar Rats.

Purpose: Echinacea purpurea (L.) Moench is a member of the Asteraceae family and is traditionally used mainly due to its immunostimulatory properties. Various compounds including alkylamides and chicoric acid were reported as active ingredients of E. purpurea. Here, we aimed to prepare electrosprayed nanoparticles (NPs) containing hydroalcoholic extract of E. purpurea using Eudragit RS100 (EP-Eudragit RS100 NPs) to improve the immunomodulatory effects of the extract. Methods: The EP-Eudragit RS100 NPs with the different extract:polymer ratios and solution concentrations were prepared using the electrospray technique. The size and morphology of the NPs were evaluated using dynamic light scattering (DLS) and field emission-scanning electron microscopy (FE-SEM). To evaluate the immune responses, male Wistar rats were administrated with the prepared EP-Eudragit RS100 NPs and plain extract in the final dose of 30 or 100 mg/kg. The blood samples of the animals were collected and the inflammatory factors and complete blood count (CBC) were investigated. Results: In vivo studies indicated that the plain extract and EP-Eudragit RS100 NPs (100 mg/kg) significantly increased the serum level of tumor necrosis factor-α (TNF-α) and interleukin 1-ß (IL1-ß) whereas the EP-Eudragit RS100 NPs (30 mg/kg) significantly increased the number of white blood cells (WBCs) compared to the control group. Lymphocytes' count in all groups was increased significantly compared to the control group (P<0.05) whereas other CBC parameters remained unchanged. Conclusion: The prepared EP-Eudragit RS100 NPs by electrospray technique caused significant reinforcement in the immunostimulatory effects of the extract of E. purpurea.

Social vulnerability predictors of drug poisoning mortality: A machine learning analysis in the United States.

BACKGROUND AND OBJECTIVES: Drug poisoning is a leading cause of unintentional deaths in the United States. Despite the growing literature, there are a few recent analyses of a wide range of community-level social vulnerability features contributing to drug poisoning mortality. Current studies on this topic face three limitations: often studying a limited subset of vulnerability features, focusing on small sample sizes, or solely including local data. To address this gap, we conducted a national-level analysis to study the impacts of several social vulnerability features in predicting drug mortality rates in the United States. METHODS: We used machine learning to investigate the role of 16 social vulnerability features in predicting drug mortality rates for US counties in 2014, 2016, and 2018-the most recent available data. We estimated each vulnerability feature's gain relative contribution in predicting drug poisoning mortality. RESULTS: Among all social vulnerability features, the percentage of noninstitutionalized persons with a disability is the most influential predictor, with a gain relative contribution of 18.6%, followed by population density and the percentage of minority residents (13.3% and 13%, respectively). Percentages of households with no available vehicles, mobile homes, and persons without a high school diploma are the following features with gain relative contributions of 6.3%, 5.8%, and 5.1%, respectively. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: We identified social vulnerability features that are most predictive of drug poisoning mortality. Public health interventions and policies targeting vulnerable communities may increase the resilience of these communities and mitigate the overdose death and drug misuse crisis.

Increasing the initiation of antiretroviral therapy through optimal placement of diagnostic technologies for pediatric HIV in Zimbabwe: A modeling analysis.

OBJECTIVES: Point-of-care (POC) devices for infant HIV testing provide timely result-return and increase antiretroviral (ART) initiation. We aimed to optimally locate POC devices to increase 30-day ART initiation in Matabeleland South, Zimbabwe. METHODS: We developed an optimization model to identify the locations for limited POC devices at health facilities, maximizing the number of infants who receive HIV test results and initiate ART within 30 days of testing. We compared location-optimization model results to non-model-based decision heuristics, which are more practical and less data-intensive. Heuristics assign POC devices based on demand, test positivity, laboratory result-return probability, and POC machine functionality. RESULTS: With the current placement of 11 existing POC machines, 37% of all tested infants with HIV were projected to receive results and 35% were projected to initiate ART within 30 days of testing. With optimal placement of existing machines, 46% were projected to receive results and 44% to initiate ART within 30 days, retaining three machines in current locations, moving eight to new facilities. Relocation based on the highest POC device functionality would be the best-performing heuristic decision (44% receiving results and 42% initiating ART withing 30 days); although, it still would not perform as well as the optimization-based approach. CONCLUSION: Optimal and ad hoc heuristic relocation of limited POC machines would increase timely result-return and ART initiation, without further, often costly, interventions. Location optimization can enhance decision-making regarding the placement of medical technologies for HIV care.

Cost-effectiveness of Increasing Buprenorphine Treatment Initiation, Duration, and Capacity Among Individuals Who Use Opioids.

Importance: Buprenorphine is an effective and cost-effective medication to treat opioid use disorder (OUD), but is not readily available to many people with OUD in the US. The current cost-effectiveness literature does not consider interventions that concurrently increase buprenorphine initiation, duration, and capacity. Objective: To conduct a cost-effectiveness analysis and compare interventions associated with increased buprenorphine treatment initiation, duration, and capacity. Design and Setting: This study modeled the effects of 5 interventions individually and in combination using SOURCE, a recent system dynamics model of prescription opioid and illicit opioid use, treatment, and remission, calibrated to US data from 1999 to 2020. The analysis was run during a 12-year time horizon from 2021 to 2032, with lifetime follow-up. A probabilistic sensitivity analysis on intervention effectiveness and costs was conducted. Analyses were performed from April 2021 through March 2023. Modeled participants included people with opioid misuse and OUD in the US. Interventions: Interventions included emergency department buprenorphine initiation, contingency management, psychotherapy, telehealth, and expansion of hub-and-spoke narcotic treatment programs, individually and in combination. Main Outcomes and Measures: Total national opioid overdose deaths, quality-adjusted life years (QALYs) gained, and costs from the societal and health care perspective. Results: Projections showed that contingency management expansion would avert 3530 opioid overdose deaths over 12 years, more than any other single-intervention strategy. Interventions that increased buprenorphine treatment duration initially were associated with an increased number of opioid overdose deaths in the absence of expanded treatment capacity. With an incremental cost- effectiveness ratio of $19 381 per QALY gained (2021 USD), the strategy that expanded contingency management, hub-and-spoke training, emergency department initiation, and telehealth was the preferred strategy for any willingness-to-pay threshold from $20 000 to $200 000/QALY gained, as it was associated with increased treatment duration and capacity simultaneously. Conclusion and Relevance: This modeling analysis simulated the effects of implementing several intervention strategies across the buprenorphine cascade of care and found that strategies that were concurrently associated with increased buprenorphine treatment initiation, duration, and capacity were cost-effective.