Evolving methodology of national tobacco control investment cases.

BACKGROUND: This article describes an investment case methodology for tobacco control that was applied in 36 countries between 2017 and 2022. METHODS: The WHO Framework Convention on Tobacco Control (FCTC) investment cases compared two scenarios: a base case that calculated the tobacco-attributable mortality, morbidity and economic costs with status quo tobacco control, and an intervention scenario that described changes in those same outcomes from fully implementing and enforcing a variety of proven, evidence-based tobacco control policies and interventions. Health consequences included the tobacco-attributable share of mortality and morbidity from 38 diseases. The healthcare expenditures and the socioeconomic costs from the prevalence of those conditions were combined to calculate the total losses due to tobacco. The monetised benefits of improvements in health resulting from tobacco control implementation were compared with costs of expanding tobacco control to assess returns on investment in each country. An institutional and context analysis assessed the political and economic dimensions of tobacco control in each context. RESULTS: We applied a rigorous yet flexible methodology in 36 countries over 5 years. The replicable model and framework may be used to inform development of tobacco control cases in countries worldwide. CONCLUSION: Investment cases constitute a tool that development partners and advocates have demanded in even greater numbers. The economic argument for tobacco control provided by this set of country-contextualised analyses can be a strong tool for policy change.

Interpreting results, impacts and implications from WHO FCTC tobacco control investment cases in 21 low-income and middle-income countries.

BACKGROUND: Tobacco control investment cases analyse the health and socioeconomic costs of tobacco use and the benefits that can be achieved from implementing measures outlined in the WHO Framework Convention on Tobacco Control (WHO FCTC). They are intended to provide policy-makers and other stakeholders with country-level evidence that is relevant, useful and responsive to national priorities and policy context. METHODS: This paper synthesises findings from investment cases conducted in Armenia, Cabo Verde, Cambodia, Chad, Colombia, Costa Rica, El Salvador, Eswatini, Georgia, Ghana, Jordan, Laos, Madagascar, Myanmar, Nepal, Samoa, Sierra Leone, Sri Lanka, Suriname, Tunisia and Zambia. We examine annual socioeconomic costs associated with tobacco use, focusing on smoking-related healthcare expenditures, the value of lives lost due to tobacco-related mortality and workplace productivity losses due to smoking. We explore potential benefits associated with WHO FCTC tobacco demand-reduction measures. RESULTS: Tobacco use results in average annual socioeconomic losses of US$95 million, US$610 million and US$1.6 billion among the low-income (n=3), lower-middle-income (n=12) and upper-middle-income countries (n=6) included in this analysis, respectively. These losses are equal to 1.1%, 1.8% and 2.9% of average annual national gross domestic product, respectively. Implementation and enforcement of WHO FCTC tobacco demand-reduction measures would lead to reduced tobacco use, fewer tobacco-related deaths and reduced socioeconomic losses. CONCLUSIONS: WHO FCTC tobacco control measures would provide a positive return on investment in every country analysed.

Advancing progress on tobacco control in low-income and middle-income countries through economic analysis.

BACKGROUND: More than 80% of the world's 1.3 billion tobacco users live in low-income and middle-income countries (LMICs), where progress to address tobacco and its harms has been slow. The perception that tobacco control detracts from economic priorities has impeded progress. The Secretariat of the WHO Framework Convention on Tobacco Control (FCTC) is leading the FCTC 2030 project, which includes technical assistance to LMICs to analyse the economic costs of tobacco use and the benefits of tobacco control. METHODS: The Secretariat of the WHO FCTC, United Nations Development Programme and WHO supported 21 LMICs between 2017 and 2022 to complete national investment cases to guide country implementation of the WHO FCTC, with analytical support provided by RTI International. These country-level cases combine customised estimates of tobacco's economic impact with qualitative analysis of socio-political factors influencing tobacco control. This paper overviews the approach, observed tobacco control advancements and learnings from 21 countries: Armenia, Cabo Verde, Cambodia, Chad, Colombia, Costa Rica, El Salvador, Eswatini, Georgia, Ghana, Jordan, Laos, Madagascar, Myanmar, Nepal, Samoa, Sierra Leone, Sri Lanka, Suriname, Tunisia and Zambia. RESULTS: Tobacco control advancements in line with investment case findings and recommendations have been observed in 17 of the 21 countries, and many have improved collaboration and policy coherence between health and economic stakeholders. CONCLUSIONS: Tobacco control must be seen as more than a health concern. Tobacco control leads to economic benefits and contributes to sustainable development. National investment cases can support country ownership and leadership to advance tobacco control.

Equity implications of tobacco taxation: results from WHO FCTC investment cases.

BACKGROUND: Across time, geographies and country income levels, smoking prevalence is highest among people with lower incomes. Smoking causes further impoverishment of those on the lower end of the income spectrum through expenditure on tobacco and greater risk of ill health. METHODS: This paper summarises the results of investment case equity analyses for 19 countries, presenting the effects of increased taxation on smoking prevalence, health and expenditures. We disaggregate the number of people who smoke, smoking-attributable mortality and cigarette expenditures using smoking prevalence data by income quintile. A uniform 30% increase in price was applied across countries. We estimated the effects of the price increase on smoking prevalence, mortality and cigarette expenditures. RESULTS: In all but one country (Bhutan), a one-time 30% increase in price would reduce smoking prevalence by the largest percent among the poorest 20% of the population. All income groups in all countries would spend more on cigarettes with a 30% increase in price. However, the poorest 20% would pay an average of 12% of the additional money spent. CONCLUSIONS: Our results confirm that health benefits from increases in price through taxation are pro-poor. Even in countries where smoking prevalence is higher among wealthier groups, increasing prices can still be pro-poor due to variable responsiveness to higher prices. The costs associated with higher smoking prevalence among the poor, together with often limited access to healthcare services and displaced spending on basic needs, result in health inequality and perpetuate the cycle of poverty.

Assessing costs of a hypertension program in primary care: evidence from the HEARTS program in Mexico.

Objective: In 2021, Mexico launched the HEARTS program to improve the prevention and control of cardiovascular disease (CVD) risk factors in 20 primary care facilities in the states of Chiapas and Yucatán. This study projects the annual cost of program implementation and discusses budgetary implications for scaling up the program. Methods: We obtained district-level data on treatment protocols, medication costs, and other resources required to prevent and treat CVD. We used the HEARTS Costing Tool to estimate total and per-patient costs. A "partial implementation" scenario calculated the costs of implementing HEARTS if existing pharmacological treatment protocols are left in place. The second scenario, "full implementation," examined costs if programs use HEARTS pharmacological protocol. Results: Respectively in the partial and full implementation scenarios, total annual costs to implement and operate HEARTS were $260 023 ($32.1 per patient/year) and $255 046 ($31.5 per patient/year) in Chiapas, and $1 000 059 ($41.3 per patient/year) and $1 013 835 ($43.3 per patient/year) in Yucatán. In Chiapas, adopting HEARTS standardized treatment protocols resulted in a 9.7 % reduction in annual medication expenditures relative to maintaining status-quo treatment approaches. In Yucatán, adoption was $12 875 more expensive, in part because HEARTS hypertension treatment regimens were more intensive than status quo regimens. Conclusion: HEARTS in the Americas offers a standardized strategy to treating and controlling CVD risk factors. In Mexico, approaches that may lead to improved program affordability include adoption of the recommended HEARTS treatment protocols with preferred medications and task shifting of services from physicians to nurses and other providers.

The case for investment in tobacco control: lessons from four countries in the Americas.

Objective: To synthesize learnings from four national tobacco control investment cases conducted in the Americas (Colombia, Costa Rica, El Salvador, Suriname) under the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) 2030 project, to describe results and how national health authorities have used the cases, and to discuss implications for the role of investment cases in advancing tobacco control. Methods: We draw on findings from four national investment cases that included 1) a cost-of-illness analysis calculating the health and economic burden of tobacco use, 2) a return-on-investment analysis of implementing key tobacco control demand reduction measures, and 3) a subsidiary analysis of one tobacco control topic of national interest (e.g., equity implications of cigarette taxation). Co-authors reported how cases have been used to advance tobacco control. Results: In Colombia, Costa Rica, El Salvador, and Suriname, tobacco use causes social and economic losses equivalent to between 1.0 to 1.8 percent of GDP. Across these countries, implementing WHO FCTC demand reduction measures would save an average of 11 400 lives per year over the next 15 years. Benefits of the measures would far outweigh the costs of implementation and enforcement. Governments are using the cases to advance tobacco control, including to improve tobacco control laws and their enforcement, strengthen tobacco taxation, prioritize tobacco control planning, coordinate a multisectoral response, and engage political leaders. Conclusions: National investment cases can help to strengthen tobacco control in countries, including by increasing public and political support for implementation of the WHO FCTC and by informing effective planning, legislation, coordination and financing.

Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries.

Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average

En general, los programas de control de la hipertensión son costo-eficaces, incluso en los países de ingresos bajos y medios. Aun así, es poco probable que los gobiernos nacionales y la sociedad civil apoyen los programas de control de la hipertensión a menos que se demuestre su valor en términos de beneficios para la salud pública, impacto presupuestario y valor de la inversión para el contexto individual del país. La Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS) implementaron la iniciativa HEARTS, un enfoque mundial estandarizado y simplificado para el control de la hipertensión, que incluye los medicamentos antihipertensivos y los dispositivos de medición de la presión arterial de preferencia. El objetivo de este estudio es informar sobre los estudios en el ámbito de la economía de la salud relativos al costo de las medidas de control de la hipertensión previstas en HEARTS (especialmente, de los medicamentos), la costo-efectividad y el impacto presupuestario, así como describir los modelos matemáticos diseñados para traducir los datos de este programa en un enfoque óptimo para la prestación y el financiamiento de los servicios de atención de la hipertensión, especialmente en países de ingresos medianos y bajos. Los primeros resultados indican que las intervenciones de HEARTS para el control de la hipertensión son de bajo costo o costo-eficaces, que el conjunto de medidas HEARTS es asequible, a un precio que oscila entre US$ 18 y US$ 44 al año por paciente tratado, y que los medicamentos antihipertensivos podrían tener un precio lo suficientemente bajo como para alcanzar un estándar medio mundial de

Geralmente, os programas de controle de hipertensão são custo-efetivos, inclusive em países de baixa e média renda, mas os governos dos países e a sociedade civil provavelmente não apoiarão tais programas a menos que demonstrem valor em termos de benefícios à saúde pública, impacto orçamentário e retorno sobre o investimento no contexto individual do país. A Organização Mundial da Saúde (OMS) e a Organização Pan-Americana da Saúde (OPAS) criaram a Global HEARTS, uma abordagem padrão e simplificada ao controle da hipertensão arterial, que inclui medicamentos anti-hipertensivos preferidos e dispositivos para aferição da pressão arterial preferidos. O objetivo deste estudo é relatar os estudos de economia em saúde que analisaram o custo (especialmente custos de medicamentos), custo-benefício e impacto orçamentário do pacote HEARTS para controle da hipertensão e descrever modelos matemáticos elaborados para traduzir os dados do programa de controle de hipertensão em uma abordagem ideal para a prestação e financiamento de serviços de atenção às pessoas com hipertensão, especialmente em países de baixa e média renda. Os primeiros resultados sugerem que as intervenções HEARTS para controle da hipertensão são de baixo custo ou custo-efetivas, que o pacote HEARTS é acessível (custando de US$ 18 a 44 por pessoa tratada por ano) e que o preço dos medicamentos anti-hipertensivos poderia ser baixo o suficiente para atingir uma média global de

Economic effects of the double burden of malnutrition.

Observations from many countries indicate that multiple forms of malnutrition might coexist in a country, a household, and an individual. In this Series, the double burden of malnutrition (DBM) encompasses undernutrition in the form of stunting, and overweight and obesity. Health effects of the DBM include those associated with both undernutrition, such as impaired childhood development and greater susceptibility to infectious diseases, and overweight, especially in terms of increased risk of added visceral fat and increased risk of non-communicable diseases. These health effects have not been translated into economic costs for individuals and economies in the form of lost wages and productivity, as well as higher medical expenses. We summarise the existing approaches to modelling the economic effects of malnutrition and point out the weaknesses of these approaches for measuring economic losses from the DBM. Where population needs suggest that nutrition interventions take into account the DBM, economic evaluation can guide the choice of so-called double-duty interventions as an alternative to separate programming for stunting and overweight. We address the evidence gap with an economic analysis of the costs and benefits of an illustrative double-duty intervention that addresses both stunting and overweight in children aged 4 years and older by providing school meals with improved quality of diet. We assess the plausibility of our method and discuss how improved data and models can generate better estimates. Double-duty interventions could save money and be more efficient than single-duty interventions.

Predicting the Effect of Single and Multiple Mutations on Protein Structural Stability.

Predicting how a point mutation alters a protein's stability can guide pharmaceutical drug design initiatives which aim to counter the effects of serious diseases. Conducting mutagenesis studies in physical proteins can give insights about the effects of amino acid substitutions, but such wet-lab work is prohibitive due to the time as well as financial resources needed to assess the effect of even a single amino acid substitution. Computational methods for predicting the effects of a mutation on a protein structure can complement wet-lab work, and varying approaches are available with promising accuracy rates. In this work we compare and assess the utility of several machine learning methods and their ability to predict the effects of single and double mutations. We in silico generate mutant protein structures, and compute several rigidity metrics for each of them. We use these as features for our Support Vector Regression (SVR), Random Forest (RF), and Deep Neural Network (DNN) methods. We validate the predictions of our in silico mutations against experimental Δ Δ G stability data, and attain Pearson Correlation values upwards of 0.71 for single mutations, and 0.81 for double mutations. We perform ablation studies to assess which features contribute most to a model's success, and also introduce a voting scheme to synthesize a single prediction from the individual predictions of the three models.

Comparing scale up of status quo hypertension care against dual combination therapy as separate pills or single pill combinations: an economic evaluation in 24 low- and middle-income countries.

Background: International hypertension treatment guidelines recommend initiating pharmacological treatment with combination therapy and using fixed dose single pill combinations (SPCs) to improve adherence. However, few countries have adopted combination therapy as a form of first-line treatment and SPC uptake in low- and middle-income countries is low due in part to cost and availability. Evidence on costs and cost-effectiveness is needed as health authorities consider incorporating new recommendations into national clinical practice guidelines. Methods: Over a 30-year time horizon, we used an Excel-based Markov cohort state-transition model to assess the financial costs (screening, treatment, program, and supply chain costs) and socio-economic outcomes (health outcomes, value of lives saved, productivity losses averted) of three antihypertensive treatment scenarios. A baseline scenario scaled treatment among adults age 30 plus while assuming continuation of the widespread practice of initiating treatment with monotherapy. Scenarios one and two scaled treatment while initiating patients on two antihypertensive medications, either as separate pills or as a SPC. Analysis inputs are informed by country-specific data, meta-analyses of the blood-pressure lowering of antihypertensive medications, and own-studies of medication costs. We compared costs, cost-effectiveness, and net-benefits across scenarios, and assessed uncertainty in a one-way sensitivity analysis. Findings: Using dual combination therapy (with or without SPCs) as first-line treatment would increase costs relative to current practices that largely use monotherapy. Required additional annual resources averaged as much as 3.6, 0.9, and 0.2 percent of government health expenditures in the analysis' low-, lower-middle, and upper-middle income countries. However, across 24 countries, over the next 30 years, combination therapy with separate pills could save 430,000 more lives and combination therapy with SPCs could save 564,000 more lives compared to baseline treatment practices. Administration of two or more medications using SPCs generated higher net benefits in most countries (16/24) compared to the baseline scenario. Interpretation: First line treatment employing SPCs is likely to generate higher net benefits compared to status quo treatment practices in countries with relatively higher incomes. To improve population health, national health systems would benefit from reducing structural and other barriers to the use of combination therapy and SPCs. Funding: This journal article was supported by TEPHINET cooperative agreement number 1NU2HGH000044-01-0 funded by the US Centers for Disease Control and Prevention.

Outcomes of a Day Wellness Program for People With Multiple Sclerosis Before and During the COVID-19 Pandemic.

BACKGROUND: The John A. Schafer, MD Multiple Sclerosis Achievement Center (MSAC) conducts wellness programs that include exercise, cognitive stimulation, education, emotional support, and socialization for people with multiple sclerosis and their care partners. Patient-reported outcomes (PROs) are collected annually. Four-year outcomes encompass the COVID-19 pandemic when some of these programs were offered virtually. METHODS: Beginning in 2017, baseline data were collected for 110 MSAC day wellness program participants through PRO measures. Of those 110, 52 completed PROs annually through 2021. Outcome measures included the Multiple Sclerosis Impact Scale (MSIS-29); Multiple Sclerosis Self-Efficacy Scale (MSSE-10); Godin Leisure-Time Exercise Questionnaire (GLTEQ); and the Neurology Quality of Life domains of Anxiety, Depression, Emotional and Behavioral Dysregulation, Positive Affect, Cognition, Ability to Participate in and Satisfaction with Social Roles and Activities, and Satisfaction with Social Roles and Activities. Analysis using t tests compared baseline with 4-year data. A separate analysis compared outcomes collected in January 2020 and January 2021. RESULTS: Analysis of 4-year data demonstrated statistically significant improvement in MSIS-29 and GLTEQ. Statistically significant improvements noted at years 2 and 3 in the Ability to Participate in Social Roles and Activities were no longer significant at year 4. Other notable changes included significant decreases in MSSE at year 4 when compared with baseline and year 3. CONCLUSIONS: Individuals who participated in a weekly, structured day wellness program showed improvements in self-reported disease impact and physical activity at year 4 vs baseline. Decreases in self-efficacy and social domains were seen, corresponding with disruptions caused by the COVID-19 pandemic. Further analysis is needed to understand the effects of the pandemic on program participants.

Scaling hypertension treatment in 24 low-income and middle-income countries: economic evaluation of treatment decisions at three blood pressure cut-points.

OBJECTIVE: Estimate the incremental costs and benefits of scaling up hypertension care in adults in 24 select countries, using three different systolic blood pressure (SBP) treatment cut-off points-≥140, ≥150 and ≥160 mm Hg. INTERVENTION: Strengthening the hypertension care cascade compared with status quo levels, with pharmacological treatment administered at different cut-points depending on the scenario. TARGET POPULATION: Adults aged 30+ in 24 low-income and middle-income countries spanning all world regions. PERSPECTIVE: Societal. TIME HORIZON: 30 years. DISCOUNT RATE: 4%. COSTING YEAR: 2020 USD. STUDY DESIGN: DATA SOURCES: Institute for Health Metrics and Evaluation's Epi Visualisations database-country-specific cardiovascular disease (CVD) incidence, prevalence and death rates. Mean SBP and prevalence-National surveys and NCD-RisC. Treatment protocols-WHO HEARTS. Treatment impact-academic literature. Costs-national and international databases. OUTCOME MEASURES: Health outcomes-averted stroke and myocardial infarction events, deaths and disability-adjusted life-years; economic outcomes-averted health expenditures, value of averted mortality and workplace productivity losses. RESULTS OF ANALYSIS: Across 24 countries, over 30 years, incremental scale-up of hypertension care for adults with SBP≥140 mm Hg led to 2.6 million averted CVD events and 1.2 million averted deaths (7% of expected CVD deaths). 68% of benefits resulted from treating those with very high SBP (≥160 mm Hg). 10 of the 12 highest-income countries projected positive net benefits at one or more treatment cut-points, compared with 3 of the 12 lowest-income countries. Treating hypertension at SBP≥160 mm Hg maximised the net economic benefit in the lowest-income countries. LIMITATIONS: The model only included a few hypertension-attributable diseases and did not account for comorbid risk factors. Modelled scenarios assumed ambitious progress on strengthening the care cascade. CONCLUSIONS: In areas where economic considerations might play an outsized role, such as very low-income countries, prioritising treatment to populations with severe hypertension can maximise benefits net of economic costs.

Current out of pocket care costs among HIV and hypertension co-morbid patients in urban and peri-urban Uganda.

BACKGROUND: Despite improvements to the cascade of HIV care in East Africa, access to care for non-communicable disease co-morbidities like hypertension (HTN) remains a persistent problem. The integration of care for these conditions presents an opportunity to achieve efficiencies in delivery as well as decrease overall costs for patients. This study aims to build evidence on the burden of current out-of-pocket costs of care among HIV-HTN co-morbid patients. METHODS: We administered a pre-tested, cross-sectional, out-of-pocket cost survey to 94 co-morbid patients receiving HIV care from 10 clinics in the Wakiso and Kampala districts of Uganda from June to November 2021. The survey assessed socio-demographic characteristics, direct medical costs (e.g., medications, consultations), indirect costs (e.g., transport, food, caregiving), and economic costs (i.e., foregone income) associated with seeking HIV and HTN care, as well as possible predictors of monthly care costs. Patients were sampled both during a government-imposed nation-wide full COVID-19 lockdown (n = 30) and after it was partially lifted (n = 64). RESULTS: Median HIV care costs constitute between 2.7 and 4.0% of median monthly household income, while HTN care costs are between 7.1 to 7.9%. For just under half of our sample, the median monthly cost of HTN care is more than 10% of household income, and more than a quarter of patients report borrowing money or selling assets to cover costs. We observe uniformly lower reported costs of care for both conditions under full COVID-19 lockdown, suggesting that access to care was limited. The main predictors of monthly HIV and HTN care costs varied by disease and costing perspective. CONCLUSIONS: Patient out of pocket costs of care for HIV and HTN were substantial, but significantly lower during the 2021 full COVID-19 lockdown in Uganda. New strategies such as service integration need to be explored to reduce these costs.

Using Stakeholder Focus Groups to Refine the Care of Pigs Used in Research.

Research organizations should be proactive in regularly evaluating and refining their animal care and use programs in order to advance animal welfare and minimize distress. Pigs are often used in research, but few empirical studies have examined optimal husbandry and research use practices for pigs in a research environment. We developed the Pig Welfare Working Group (PWWG) to address the need for more formal guidelines on the management and use of pigs in research. The PWWG was a stakeholder focus group whose goal was to identify challenges and opportunities relevant to improving animal welfare through collaboration, knowledge sharing, and inclusive decision-making. Through consensus building, the PWWG developed 12 recommendations for behavioral management, housing, research procedures, transportation, and rehoming programs. The recommendations were rolled out across the contract research organization, business units, sites, and countries. Follow up will be conducted regularly to assess welfare, monitor progress toward implementing the recommendations, and recognize and reward participants making changes at their site.

Orchestrating a New Path for Multiple Sclerosis: Achieving Physical, Cognitive, and Emotional Rehabilitation Goals Through Physical and Music Therapy.

BACKGROUND: Interdisciplinary therapies for the management of people with multiple sclerosis (MS) are underappreciated. There is an urgent need to introduce music therapy (MT), either alone or in combination with physical therapy (PT), into clinical practice to achieve synergy with disease-modifying therapies. A holistic approach to rehabilitation for people with MS may mitigate symptoms and reduce polypharmacy, potentially lowering health care costs. RESULTS: As MS progresses, patients experience a range of worsening symptoms, and many develop psychosocial comorbidities. As disease-modifying therapies delay disability progression, nonpharmacologic treatments become increasingly important. The main aim of PT is to improve or maintain patients' functional mobility, strength, and flexibility. Because it targets multiple functions, MT can help improve functional and psychosocial domains and may be a valuable intervention to help patients achieve the physical, cognitive, and emotional goals of PT. Exploratory studies showed that MT, alone or in combination with PT, can lead to functional improvements in mobility, balance, gait, and fatigue. Similar to PT, MT also has benefits in improving fine motor skills, cognition, learning, and memory and in providing emotional support. CONCLUSIONS: Both MT and PT have the potential to improve overall well-being and health-related quality of life in physically active patients with MS, and MT can provide added emotional support for those who are less able to engage in physical activity. However, MT is not typically a part of standard of care, and PT visits are limited. Nevertheless, interdisciplinary therapies should be incorporated into clinical practice.

Economic evaluation of implementation science outcomes in low- and middle-income countries: a scoping review.

BACKGROUND: Historically, the focus of cost-effectiveness analyses has been on the costs to operate and deliver interventions after their initial design and launch. The costs related to design and implementation of interventions have often been omitted. Ignoring these costs leads to an underestimation of the true price of interventions and biases economic analyses toward favoring new interventions. This is especially true in low- and middle-income countries (LMICs), where implementation may require substantial up-front investment. This scoping review was conducted to explore the topics, depth, and availability of scientific literature on integrating implementation science into economic evaluations of health interventions in LMICs. METHODS: We searched Web of Science and PubMed for papers published between January 1, 2010, and December 31, 2021, that included components of both implementation science and economic evaluation. Studies from LMICs were prioritized for review, but papers from high-income countries were included if their methodology/findings were relevant to LMIC settings. RESULTS: Six thousand nine hundred eighty-six studies were screened, of which 55 were included in full-text review and 23 selected for inclusion and data extraction. Most papers were theoretical, though some focused on a single disease or disease subset, including: mental health (n = 5), HIV (n = 3), tuberculosis (n = 3), and diabetes (n = 2). Manuscripts included a mix of methodology papers, empirical studies, and other (e.g., narrative) reviews. Authorship of the included literature was skewed toward high-income settings, with 22 of the 23 papers featuring first and senior authors from high-income countries. Of nine empirical studies included, no consistent implementation cost outcomes were measured, and only four could be mapped to an existing costing or implementation framework. There was also substantial heterogeneity across studies in how implementation costs were defined, and the methods used to collect them. CONCLUSION: A sparse but growing literature explores the intersection of implementation science and economic evaluation. Key needs include more research in LMICs, greater consensus on the definition of implementation costs, standardized methods to collect such costs, and identifying outcomes of greatest relevance. Addressing these gaps will result in stronger links between implementation science and economic evaluation and will create more robust and accurate estimates of intervention costs. TRIAL REGISTRATION: The protocol for this manuscript was published on the Open Science Framework. It is available at: https://osf.io/ms5fa/ (DOI: 10.17605/OSF.IO/32EPJ).

Correction: The investment case as a mechanism for addressing the NCD burden: Evaluating the NCD institutional context in Jamaica, and the return on investment of select interventions.

[This corrects the article DOI: 10.1371/journal.pone.0223412.].

Assessing costs of a hypertension management program: An application of the HEARTS costing tool in a program planning workshop in Thailand.

The HEARTS technical package, a part of the Global Hearts Initiative to improve cardiovascular health globally, is a strategic approach for cardiovascular disease prevention and control at the primary care level. To support the evaluation of costs associated with HEARTS program components, a costing tool was developed to evaluate the incremental cost of program implementation. This report documents an application of the HEARTS costing tool during a costing workshop prior to the initiation of a HEARTS pilot program in Thailand's Phothong District, 2019-2020. During the workshop, a mock exercise was conducted to estimate the expected costs of the pilot study. The workshop application of the tool underscored its applicability to the HEARTS program planning process by identifying cost drivers associated with individual program elements. It further illustrated that by supporting disaggregation of costs into fixed and variable categories, the tool can inform the scalability of pilot projects to larger populations. Lessons learned during the initial development and application of the costing tool can inform future HEARTS evaluation efforts.

Atropisomeric small molecule Bcl-2 ligands: determination of bioactive conformation.

The separation of atropisomeric conformers of 1,2,3,4-tetrahydroisoquinoline amide Bcl-2 ligands allowed the identification of the bioactive conformer which was subsequently confirmed by X-ray crystallography.