Analysis of mammography screening schedules under varying resource constraints for planning breast cancer control programs in low- and middle-income countries : a mathematical study

Background. Low-and-middle-income countries (LMICs) have higher mortality-to-incidence ratio for breast cancer compared to high-income countries (HICs) because of late-stage diagnosis. Mammography screening is recommended for early diagnosis, however, the infrastructure capacity in LMICs are far below that needed for adopting current screening guidelines. Current guidelines are extrapolations from HICs, as limited data had restricted model development specific to LMICs, and thus, economic analysis of screening schedules specific to infrastructure capacities are unavailable. Methods. We applied a new Markov process method for developing cancer progression models and a Markov decision process model to identify optimal screening schedules under a varying number of lifetime screenings per person, a proxy for infrastructure capacity. We modeled Peru, a middle-income country, as a case study and the United States, an HIC, for validation. Results. Implementing 2, 5, 10, and 15 lifetime screens would require about 55, 135, 280, and 405 mammography machines, respectively, and would save 31, 62, 95, and 112 life-years per 1000 women, respectively. Current guidelines recommend 15 lifetime screens, but Peru has only 55 mammography machines nationally. With this capacity, the best strategy is 2 lifetime screenings at age 50 and 56 years. As infrastructure is scaled up to accommodate 5 and 10 lifetime screens, screening between the ages of 44-61 and 41-64 years, respectively, would have the best impact. Our results for the United States are consistent with other models and current guidelines. Limitations. The scope of our model is limited to analysis of national-level guidelines. We did not model heterogeneity across the country. Conclusions. Country-specific optimal screening schedules under varying infrastructure capacities can systematically guide development of cancer control programs and planning of health investments

The epidemiology of Leishmania donovani infection in high transmission foci in India.

OBJECTIVE: Visceral Leishmaniasis (VL) is highly prevalent in Bihar, India. India and its neighbours aim at eliminating VL, but several knowledge gaps in the epidemiology of VL may hamper that effort. The prevalence of asymptomatic infections with Leishmania donovani and their role in transmission dynamics are not well understood. We report data from a sero-survey in Bihar. METHODS: Demographic and immunological surveys were carried out in July and November 2006, respectively in 16 highly VL endemic foci in Muzaffarpur district in Bihar. Household and individual information was gathered and capillary blood samples were collected on filter papers. Direct agglutination test (DAT) was used to determine infected individuals (cut-off titre 1:1600). DAT results were tabulated against individual and household variables. A multivariate generalized estimating equation (GEE) model was used to study the prevalence of serologically positive individuals taking into account the clustering at household and cluster levels. RESULTS: Of study subjects 18% were DAT positive, and this proportion increased with age. Women had a significantly lower prevalence than men >14 years old. Owning domestic animals (cows, buffaloes or goats) was associated with a higher risk of being DAT positive [OR 1.16 (95% CI 1.01-1.32)], but socio-economic status was not. CONCLUSIONS: Prevalence of leishmanial antibodies was high in these communities, but variable. Demographic factors (i.e. marriage) may explain the lower DAT positivity in women >14 years of age. Within these homogeneously poor communities, socio-economic status was not linked to L. donovani infection risk at the individual level, but ownership of domestic animals was

Prioritizing surveillance activities for certification of yaws eradication based on a review and model of historical case reporting

BACKGROUNDt: The World Health Organization (WHO) has targeted yaws for global eradication. Eradication requires certification that all countries are yaws-free. While only 14 Member States currently report cases to WHO, many more are known to have a history of yaws and some of them may have ongoing transmission. We reviewed the literature and developed a model of case reports to identify countries in which passive surveillance is likely to find and report cases if transmission is still occurring, with the goal of reducing the number of countries in which more costly active surveillance will be required. METHODSt: We reviewed published and unpublished documents to extract data on the number of yaws cases reported to WHO or appearing in other literature in any year between 1945 and 2015. We classified countries as: a) having interrupted transmission; b) being currently endemic; c) being previously endemic (current status unknown); or d) having no history of yaws. We constructed a panel dataset for the years 1945-2015 and ran a regression model to identify factors associated with some countries not reporting cases during periods when there was ongoing (and documented) transmission. For previously endemic countries whose current status is unknown, we then estimated the probability that countries would have reported cases if there had in fact been transmission in the last three years (2013-2015)." - Label: RESULTS content: Yaws has been reported in 103 of the 237 countries and areas considered. 14 Member States and 1 territory (Wallis and Futuna Islands) are currently endemic. 2 countries are believed to have interrupted transmission. 86 countries and areas are previously endemic (current status unknown). Reported cases peaked in the 1950s, with 55 countries reporting at least one case in 1950 and a total of 2.35 million cases reported in 1954. Our regression model suggests that case reporting during periods of ongoing transmission is positively associated with socioeconomic development and, in the short-term, negatively associated with independence. We estimated that for 66 out of the 86 previously endemic countries whose current status is unknown, the probability of reporting cases in the absence of active surveillance is less than 50%. DISCUSSION: Countries with a history of yaws need to be prioritized so that international resources for global yaws eradication may be deployed efficiently. Heretofore, the focus has been on mass treatment in countries currently reporting cases. It is also important to undertake surveillance in the 86 previously endemic countries for which the current status is unknown. Within this large and diverse group, we have identified a group of 20 countries with more than a 50% probability of reporting cases in the absence of active surveillance. For the other 66 countries, international support for active surveillance will likely be required

The cost and cost-effectiveness of rapid testing strategies for yaws diagnosis and surveillance.

BACKGROUND: Yaws is a non-venereal treponemal infection caused by Treponema pallidum subspecies pertenue. The disease is targeted by WHO for eradication by 2020. Rapid diagnostic tests (RDTs) are envisaged for confirmation of clinical cases during treatment campaigns and for certification of the interruption of transmission. Yaws testing requires both treponemal (trep) and non-treponemal (non-trep) assays for diagnosis of current infection. We evaluate a sequential testing strategy (using a treponemal RDT before a trep/non-trep RDT) in terms of cost and cost-effectiveness, relative to a single-assay combined testing strategy (using the trep/non-trep RDT alone), for two use cases: individual diagnosis and community surveillance. METHODS: We use cohort decision analysis to examine the diagnostic and cost outcomes. We estimate cost and cost-effectiveness of the alternative testing strategies at different levels of prevalence of past/current infection and current infection under each use case. We take the perspective of the global yaws eradication programme. We calculate the total number of correct diagnoses for each strategy over a range of plausible prevalences. We employ probabilistic sensitivity analysis (PSA) to account for uncertainty and report 95% intervals. RESULTS: At current prices of the treponemal and trep/non-trep RDTs, the sequential strategy is cost-saving for individual diagnosis at prevalence of past/current infection less than 85% (81-90); it is cost-saving for surveillance at less than 100%. The threshold price of the trep/non-trep RDT (below which the sequential strategy would no longer be cost-saving) is US$1.08 (1.02-1.14) for individual diagnosis at high prevalence of past/current infection (51$ 0.54 (0.52-0.56) for community surveillance at low prevalence (15%). DISCUSSION: We find that the sequential strategy is cost-saving for both diagnosis and surveillance in most relevant settings. In the absence of evidence assessing relative performance (sensitivity and specificity), cost-effectiveness is uncertain. However, the conditions under which the combined test only strategy might be more cost-effective than the sequential strategy are limited. A cheaper trep/non-trep RDT is needed, costing no more than US$ 0.50-1.00, depending on the use case. Our results will help enhance the cost-effectiveness of yaws programmes in the 13 countries known to be currently endemic. It will also inform efforts in the much larger group of 71 countries with a history of yaws, many of which will have to undertake surveillance to confirm the interruption of transmission

What determines the effects and costs of breast cancer screening?

__Background:__ Multiple reviews demonstrated high variability in effectiveness and cost-effectiveness outcomes among studies on breast cancer screening (BCS) programmes. No study to our knowledge has summarized the current evidence on determinants of effectiveness and cost-effectiveness of the most used BCS approaches or tried to explain differences in conclusions of systematic reviews on this topic. Based on published reviews, this systematic review aims to assess the degree of variability of determinants for (a) effectiveness and (b) cost-effectiveness of BCS programmes using mammography, clinical breast examination, breast self-examination, ultrasonography, or their combinations among the general population. __Methods:__ We will perform a comprehensive systematic literature search in Cochrane, Scopus, Embase, and Medline (via Pubmed). The search will be supplemented with hand searching of references of the included reviews, with hand searching in the specialized journals, and by contacting prominent experts in the field. Additional search for grey literature will be conducted on the websites of international cancer associations and networks. Two trained research assistants will screen titles and abstracts of publications independently, with at least random 10% of all abstracts being also screened by the principal researcher. The full texts of the systematic reviews will then be screened independently by two authors, and disagreements will be solved by consensus. The included reviews will be grouped by publication year, outcomes, designs of original studies, and quality. Additionally, for reviews published since 2011, transparency in reporting will be assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for the review on determinants of effectiveness and a modified PRISMA checklist for the review on determinants for cost-effectiveness. The study will apply the Assessing the Methodological Quality of Systematic Reviews checklist to assess the methodological quality of systematic reviews. We will report the data extracted from the systematic reviews in a systematic format. Meta-meta-analysis of extracted data will be conducted when feasible. __Discussion:__ This systematic review of reviews will examine the degree of variability in the effectiveness and cost-effectiveness of BCS programmes. _Systematic review registration:_ PROSPERO CRD42016050764and CRD42016050765

What determines the effects and costs of breast cancer screening?

__Background:__ Multiple reviews demonstrated high variability in effectiveness and cost-effectiveness outcomes among studies on breast cancer screening (BCS) programmes. No study to our knowledge has summarized the current evidence on determinants of effectiveness and cost-effectiveness of the most used BCS approaches or tried to explain differences in conclusions of systematic reviews on this topic. Based on published reviews, this systematic review aims to assess the degree of variability of determinants for (a) effectiveness and (b) cost-effectiveness of BCS programmes using mammography, clinical breast examination, breast self-examination, ultrasonography, or their combinations among the general population. __Methods:__ We will perform a comprehensive systematic literature search in Cochrane, Scopus, Embase, and Medline (via Pubmed). The search will be supplemented with hand searching of references of the included reviews, with hand searching in the specialized journals, and by contacting prominent experts in the field. Additional search for grey literature will be conducted on the websites of international cancer associations and networks. Two trained research assistants will screen titles and abstracts of publications independently, with at least random 10% of all abstracts being also screened by the principal researcher. The full texts of the systematic reviews will then be screened independently by two authors, and disagreements will be solved by consensus. The included reviews will be grouped by publication year, outcomes, designs of original studies, and quality. Additionally, for reviews published since 2011, transparency in reporting will be assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist for the review on determinants of effectiveness and a modified PRISMA checklist for the review on determinants for cost-effectiveness. The study will apply the Assessing the Methodological Quality of Systematic Reviews checklist to assess the methodological quality of systematic reviews. We will report the data extracted from the systematic reviews in a systematic format. Meta-meta-analysis of extracted data will be conducted when feasible. __Discussion:__ This systematic review of reviews will examine the degree of variability in the effectiveness and cost-effectiveness of BCS programmes. _Systematic review registration:_ PROSPERO CRD42016050764and CRD42016050765

Towards a coherent global framework for health financing: recommendations and recent developments

The articles in this special issue have demonstrated how unprecedented transitions have come with both challenges and opportunities for health financing. Against the background of these challenges and opportunities, the Working Group on Health Financing at the Chatham House Centre on Global Health Security laid out, in 2014, a set of policy responses encapsulated in 20 recommendations for how to make progress towards a coherent global framework for health financing. These recommendations pertain to domestic financing of national health systems, global public goods for health, external financing for national health systems and the cross-cutting issues of accountability and agreement on a new global framework. Since the Working Group concluded its work, multiple events have reinforced the group’s recommendations. Among these are the agreement on the Addis Ababa Action Agenda, the adoption of the Sustainable Development Goals, the outbreak of Ebola in West Africa and the release of the Panama Papers. These events also represent new stepping stones towards a new global framework

Systematic reviews as a 'lens of evidence': Determinants of benefits and harms of breast cancer screening

This systematic review, stimulated by inconsistency in secondary evidence, reports the benefits and harms of breast cancer (BC) screening and their determinants according to systematic reviews. A systematic search, which identified 9,976 abstracts, led to the inclusion of 58 reviews. BC mortality reduction with screening mammography was 15–25% in trials and 28–56% in observational studies in all age groups, and the risk of stage III+ cancers was reduced for women older than 49 years. Overdiagnosis due to mammography was 1–60% in trials and 1–12% in studies with a low risk of bias, and cumulative falsepositive rates were lower with biennial than annual screening (3–17% vs 0.01–41%). There is no consistency in the reviews’ conclusions about the magnitude of BC mortality reduction among women younger than 50 years or older than 69 years, or determinants of benefits and harms of mammography, including the type of mammography (digital vs screen-film), the number of views and the screening interval. Similarly, there was no solid evidence on determinants of benefits and harms or BC mortality reduction with screening by ultrasonography or clinical breast examination (sensitivity ranges, 54–84% and 47–69%, respectively), and strong evidence of unfavourable benefit-to-harm ratio with breast self-examination. The reviews’ conclusions were not dependent on the quality of the reviews or publication date. Systematic reviews on mammography screening, mainly from high-income countries, systematically disagree on the interpretation of the benefit-to-harm ratio. Future reviews are unlikely to clarify the discrepancies unless new original studies are published

Human African Trypanosomiasis in a Rural Community, Democratic Republic of Congo

Human African trypanosomiasis places a substantial economic hardship on affected households

Cost-effectiveness of Algorithms for Confirmation Test of Human African Trypanosomiasis

Algorithms that incorporate concentration techniques are more effective and efficient than the currently used algorithms