Comparative assessment of the cost-effectiveness of Tuberculosis (TB) active case-finding interventions: A systematic analysis of TB REACH wave 5 projects.

PURPOSE: Interventions that can help streamline and reduce gaps in the tuberculosis (TB) care cascade can play crucial roles in TB prevention and care, but are often operationally complex and resource intensive, given the heterogenous settings in which they are implemented. In this study, we present a comparative analysis on cost-effectiveness of TB REACH Wave 5 projects with diverse programmatic objectives to inform future decisions regarding funding, strategic adoption, and scale-up. METHODS: We comprehensively reviewed project reports and financial statements from TB REACH Wave 5, a funding mechanism for interventions that aimed to strengthen the TB care cascade in diverse settings. Two independent reviewers abstracted cost (in 2017 US dollars) and key programmatic data, including project type (case-finding only; case-finding and linkage-to-care; or case-finding, linkage-to-care and patient support), operational setting (urban or rural), and project outputs (numbers of people with TB diagnosed, started on treatment, and successfully completing treatment). Cost-effectiveness ratios for each project were calculated as ratios of apportioned programmatic expenditures to corresponding project outputs. RESULTS: Of 32 case finding and patient support projects funded through TB REACH Wave 5, 29 were included for analysis (11 case-finding only; 9 case-finding and linkage-to-care; and 9 case-finding, linkage-to-care and patient support). 21 projects (72%) were implemented in either Africa or Southeast Asia, and 19 (66%) focused on serving urban areas. Average cost-effectiveness was $184 per case diagnosed (range: $30-$10,497), $332 per diagnosis and treatment initiation ($123-$10,608), and $40 per patient treatment supported ($8-$160). Cost per case diagnosed was lower for case-finding-only projects ($132) than projects including linkage-to-care ($342) or linkage-to-care and patient support ($254), and generally increased with the corresponding country's per-capita GDP ($543 per $1000 increase, 95% confidence interval: -$53, $1138). CONCLUSION: The costs and cost-effectiveness of interventions to strengthen the TB care cascade were heterogenous, reflecting differences in context and programmatic objective. Nevertheless, many such interventions are likely to offer good value for money. Systematic collection and analysis of cost-effectiveness data can help improve comparability, monitoring, and evaluation.

Acute Limb Ischemia After Self-Injection of Crushed Morphine Tablets into the Radial Artery: Role of Infrared Thermography in the Assessment of Tissue Perfusion.

BACKGROUND This article presents a case involving complications after intentional injection of crushed tablets into the arterial circulation, its diagnosis, and the treatment adopted. The diagnosis process illustrates the potential of techniques based on thermal imaging as tools to assess tissue perfusion. Inadvertent intravenous injection of crushed tablets is more common, but there are few reports on arterial circulation, and no studies were found on the self-injection of crushed morphine tablets, particularly into the radial artery. CASE REPORT A 51-year-old man with alcoholism and a history of illegal drug usage intentionally self-injected 3 crushed morphine tablets into his right radial artery. The patient progressed with compartment syndrome, requiring decompressive fasciotomy of the right forearm and ischemia of the right fingers, which were amputated. He presented with rhabdomyolysis and required dialysis. The patient agreed to full heparinization, corticotherapy, and the use of nitroglycerin and prostaglandin E1. Due to the progression of the necrotic area, the patient underwent proximal phalanx excision and surgical reconstruction of the right-hand remnant. CONCLUSIONS The injection of morphine tablets into circulation caused severe complications, which led to the excision of the proximal phalanx and the surgical reconstruction of the remnant of the right hand. In the present case, infrared thermography proved to be an effective method in assessing tissue perfusion.

Cost-effectiveness of scaling up short course preventive therapy for tuberculosis among children across 12 countries.

BACKGROUND: While household contact investigation is widely recommended as a means to reduce the burden of tuberculosis (TB) among children, only 27% of eligible pediatric household contacts globally received preventive treatment in 2018. We assessed the cost-effectiveness of household contact investigation for TB treatment and short-course preventive therapy provision for children under 15 years old across 12 high TB burden countries. METHODS: We used decision analysis to compare the costs and estimated effectiveness of three intervention scenarios: (a) status quo (existing levels of coverage with isoniazid preventive therapy), (b) contact investigation with treatment of active TB but no additional preventive therapy, and (c) contact investigation with TB treatment and provision of short-course preventive therapy. Using country-specific demographic, epidemiological and cost data from the literature, we estimated annual costs (in 2018 USD) and the number of TB cases and deaths averted across 12 countries. Incremental cost effectiveness ratios were assessed as cost per death and per disability-adjusted life year [DALY] averted. FINDINGS: Our model estimates that contact investigation with treatment of active TB and provision of preventive therapy could be highly cost-effective compared to the status quo (ranging from $100 per DALY averted in Malawi to $1,600 in Brazil; weighted average $383 per DALY averted [uncertainty range: $248 - $1,130]) and preferred to contact investigation without preventive therapy (weighted average $751 per DALY averted [uncertainty range: $250 - $1,306]). Key drivers of cost-effectiveness were TB prevalence, sensitivity of TB diagnosis, case fatality for untreated TB, and cost of household screening. INTERPRETATION: Based on this modeling analysis of available published data, household contact investigation with provision of short-course preventive therapy for TB has a value-for-money profile that compares favorably with other interventions. FUNDING: Unitaid (2017-20-IMPAACT4TB).

Sub-district level correlation between tuberculosis notifications and socio-demographic factors in Dhaka City corporation, Bangladesh.

We developed a novel method to align two data sources (TB notifications and the Demographic Health Survey, DHS) captured at different geographic scales. We used this method to identify sociodemographic indicators - specifically population density - that were ecologically correlated with elevated TB notification rates across wards (~100 000 people) in Dhaka, Bangladesh. We found population density was the variable most closely correlated with ward-level TB notification rates (Spearman's rank correlation 0.45). Our approach can be useful, as publicly available data (e.g. DHS data) could help identify factors that are ecologically associated with disease burden when more granular data (e.g. ward-level TB notifications) are not available. Use of this approach might help in designing spatially targeted interventions for TB and other diseases in settings of weak existing data on disease burden at the subdistrict level.

Model-based Cost-effectiveness of State-level Latent Tuberculosis Interventions in California, Florida, New York, and Texas.

BACKGROUND: Targeted testing and treatment (TTT) for latent tuberculosis (TB) infection (LTBI) is a recommended strategy to accelerate TB reductions and further TB elimination in the United States. Evidence on cost-effectiveness of TTT for key populations can help advance this goal. METHODS: We used a model of TB transmission to estimate the numbers of individuals who could be tested by interferon-γ release assay and treated for LTBI with 3 months of self-administered rifapentine and isoniazid (3HP) under various TTT scenarios. Specifically, we considered rapidly scaling up TTT among people who are non-US-born, diabetic, living with human immunodeficiency virus (HIV), homeless or incarcerated in California, Florida, New York, and Texas-states where more than half of US TB cases occur. We projected costs (from the healthcare system perspective, in 2018 dollars), 30-year reductions in TB incidence, and incremental cost-effectiveness (cost per quality-adjusted life-year [QALY] gained) for TTT in each modeled population. RESULTS: The projected cost-effectiveness of TTT differed substantially by state and population, while the health impact (number of TB cases averted) was consistently greatest among non-US-born individuals. TTT was most cost-effective among persons with HIV (from $2828/QALY gained in Florida to $11 265/QALY gained in New York) and least cost-effective among people with diabetes (from $223 041/QALY gained in California to $817 753/QALY in New York). CONCLUSIONS: The modeled cost-effectiveness of TTT for LTBI varies across states but was consistently greatest among people with HIV; moderate among people who are non-US-born, incarcerated, or homeless; and least cost-effective among people with diabetes.

Costing the implementation of public health interventions in resource-limited settings: a conceptual framework.

BACKGROUND: Failing to account for the resources required to successfully implement public health interventions can lead to an underestimation of costs and budget impact, optimistic cost-effectiveness estimates, and ultimately a disconnect between published evidence and public health decision-making. METHODS: We developed a conceptual framework for assessing implementation costs. We illustrate the use of this framework with case studies involving interventions for tuberculosis and HIV/AIDS in resource-limited settings. RESULTS: Costs of implementing public health interventions may be conceptualized as occurring across three phases: design, initiation, and maintenance. In the design phase, activities include developing intervention components and establishing necessary infrastructure (e.g., technology, standard operating procedures). Initiation phase activities include training, initiation of supply chains and quality assurance procedures, and installation of equipment. Implementation costs in the maintenance phase include ongoing technical support, monitoring and evaluation, and troubleshooting unexpected obstacles. Within each phase, implementation costs can be incurred at the site of delivery ("site-specific" costs) or more centrally ("above-service" or "central" costs). For interventions evaluated in the context of research studies, implementation costs should be classified as programmatic, research-related, or shared research/program costs. Purely research-related costs are often excluded from analysis of programmatic implementation. CONCLUSIONS: In evaluating public health interventions in resource-limited settings, accounting for implementation costs enables more realistic estimates of budget impact and cost-effectiveness and provides important insights into program feasibility, scale-up, and sustainability. Assessment of implementation costs should be planned prospectively and performed in a standardized manner to ensure generalizability.