The cost and cost-effectiveness of alternative strategies to expand treatment to HIV-positive South Africans: scale economies and outreach costs

This repository item contains a single issue of the Health and Development Discussion Papers, an informal working paper series that began publishing in 2002 by the Boston University Center for Global Health and Development. It is intended to help the Center and individual authors to disseminate work that is being prepared for journal publication or that is not appropriate for journal publication but might still have value to readers.The South African government is currently discussing various alternative approaches to the further expansion of antiretroviral treatment (ART) in public-sector facilities. We used the EMOD-HIV model, a HIV transmission model which projects South African HIV incidence and prevalence and ARV treatment by age-group for alternative combinations of treatment eligibility criteria and testing, to generate 12 epidemiological scenarios. Using data from our own bottom-up cost analyses in South Africa, we separate outpatient cost into nonscale- dependent costs (drugs and laboratory tests) and scale-dependent cost (staff, space, equipment and overheads) and model the cost of production according to the expected future number and size of clinics. On the demand side, we include the cost of creating and sustaining the projected incremental demand for testing and treatment. Previous research with EMOD-HIV has shown that more vigorous recruitment of patients with CD4 counts less than 350 is an advantageous policy over a five-year horizon. Over 20 years, however, the model assumption that a person on treatment is 92% less infectious improves the cost-effectiveness of higher eligibility thresholds, averting HIV infections for between $1,700 and$2,800, while more vigorous expansion under the current guidelines would cost more than $7,500 per incremental HIV infection averted. Based on analysis of the sensitivity of the results to 1,728 alternative parameter combinations at each of four discount rates, we conclude that better knowledge of the behavioral elasticities could reduce the uncertainty of cost estimates by a factor of 4 to 10

OVC cost model

This item is archived in the repository for materials published for the USAID supported Orphans and Vulnerable Children Comprehensive Action Research Project (OVC-CARE) at the Boston University Center for Global Health and Development

Interobserver agreement of Thyroid Imaging Reporting and Data System (TIRADS) and strain elastography for the assessment of thyroid nodules

Background: Thyroid Imaging Reporting and Data System (TIRADS) was developed to improve patient management and cost-effectiveness by avoiding unnecessary fine needle aspiration biopsy (FNAB) in patients with thyroid nodules. However, its clinical use is still very limited. Strain elastography (SE) enables the determination of tissue elasticity and has shown promising results for the differentiation of thyroid nodules. Methods: The aim of the present study was to evaluate the interobserver agreement (IA) of TIRADS developed by Horvath et al. and SE. Three blinded observers independently scored stored images of TIRADS and SE in 114 thyroid nodules (114 patients). Cytology and/or histology was available for all benign (n = 99) and histology for all malignant nodules (n = 15). Results: The IA between the 3 observers was only fair for TIRADS categories 2–5 (Coheńs kappa = 0.27,p = 0.000001) and TIRADS categories 2/3 versus 4/5 (ck = 0.25,p = 0.0020). The IA was substantial for SE scores 1–4 (ck = 0.66,p<0.000001) and very good for SE scores 1/2 versus 3/4 (ck = 0.81,p<0.000001). 92–100% of patients with TIRADS-2 had benign lesions, while 28–42% with TIRADS-5 had malignant cytology/histology. The negative-predictive-value (NPV) was 92–100% for TIRADS using TIRADS-categories 4&5 and 96–98% for SE using score ES-3&4 for the diagnosis of malignancy, respectively. However, only 11–42% of nodules were in TIRADS-categories 2&3, as compared to 58–60% with ES-1&2. Conclusions: IA of TIRADS developed by Horvath et al. is only fair. TIRADS and SE have high NPV for excluding malignancy in the diagnostic work-up of thyroid nodules

The economics of antiretroviral therapy in South Africa: The role of budget impact modelling in changing policy

South Africa is home to the largest number of people living with HIV in the world, as well as the world’s largest public-sector antiretroviral treatment (ART) programme. Despite the absolute majority of it being domestically funded, planning and budgeting for this programme has in the past been based on assumptions regarding target population and unit cost and on politically expedient coverage targets. The aim of this thesis was to improve on this situation by developing a budget impact model that could project the number of adults and children in treatment based on sound epidemiological methods, and calculate the cost of treating them based on the results of detailed bottom-up cost analyses at relevant clinics and hospitals in South Africa. The thesis describes the methods used in generating the inputs for the model, including the outpatient and inpatient cost of ART provision to adults and children of different ages, and the rates of CD4 cell count development, mortality, loss to follow-up, treatment failure, and regimen switches that were used in the model.The model was used to illustrate the budget impact of a number of guideline changes under discussion by the South African government in 2009/10, including 1.) expanding eligibility to all adults with CD4 cell counts <350 cells/microl, as well as to all TB co-infected and pregnant patients and all children under the age of 12 months regardless of immunological status, and 2.) replacing stavudine in first-line regimens with tenofovir for adults and with abacavir for children, with concomitant changes to second-line regimens. Both 1.) and 2.) had been suggested by the 2009 World Health Organization (WHO) guidelines (“Full WHO guidelines”). A second scenario was considered that expanded eligibility at 350 CD4 cells/microl only to those adults who were pregnant or had active TB at initiation while also replacing the current drug regimens as under 2.) (“New guidelines”). Additional factors with an impact on cost that were considered in the model were a) the introduction of a task-shifting policy that allowed antiretroviral drugs to be prescribed by nurses instead of doctors, and dispensed by pharmacy assistants instead of pharmacists, and b) replacing the existing system of antiretroviral drug procurement via government tenders that favour domestic production with drugs sourced globally at ceiling prices based on the cheapest internationally available price for each drug, including fixed-dose combinations (FDCs) wherever possible. Combining all the inputs, the model showed that while the Full WHO guidelines scenario would increase total cost over the next two mid-term expenditure framework periods (2010/11 to 2016/17) by 35% to USD 19.1 billion, and the New Guidelines scenario by 19%, this increase could be more than offset by introducing the two additional policies. In this case, the total cost of the ART programme under the New Guidelines would be 32% less than under the Old Guidelines without FDCs and task-shifting (taken as government’s revealed willingness-to-pay), while reaching 14% more patients, and implementing the Full WHO Guidelines would still be 23% less costly than continuing the Old Guidelines, while reaching 23% more patients. Based in part on this analysis, the South African government increased treatment eligibility in two steps in April 2010 and in August 2011, introduced the improved drug regimens, established task shifting, and, using the proposed reference price list, negotiated significant drug price reductions for both the December 2010 and the December 2012 ARV drug tender. The budget impact model, named the National ART Cost Model, has been used in budget planning processes for the last seven financial years and, based in part on it, the government’s Conditional Grant for HIV/AIDS, the main vehicle for ART funding, was more than doubled in real terms over this time period. The thesis ends by presenting the results of a cost-benefit analysis of an alternative funding mechanism to public-sector funding, the provision of ART at the workplace, which was found from the company perspective to be cost-saving over no provision of ART, reducing the total cost due to HIV by 5%, and the cost per HIV-infected employee by 14%, over 20 years

Acoustic radiation force impulse imaging for differentiation of thyroid nodules

Background: Acoustic Radiation Force Impulse (ARFI)-imaging is an ultrasound-based elastography method enabling quantitative measurement of tissue stiffness. The aim of the present study was to evaluate sensitivity and specificity of ARFI-imaging for differentiation of thyroid nodules and to compare it to the well evaluated qualitative real-time elastography (RTE). Methods: ARFI-imaging involves the mechanical excitation of tissue using acoustic pulses to generate localized displacements resulting in shear-wave propagation which is tracked using correlation-based methods and recorded in m/s. Inclusion criteria were: nodules $5 mm, and cytological/histological assessment. All patients received conventional ultrasound, real-time elastography (RTE) and ARFI-imaging. Results: One-hundred-fifty-eight nodules in 138 patients were available for analysis. One-hundred-thirty-seven nodules were benign on cytology/histology, and twenty-one nodules were malignant. The median velocity of ARFI-imaging in the healthy thyroid tissue, as well as in benign and malignant thyroid nodules was 1.76 m/s, 1.90 m/s, and 2.69 m/s, respectively. While no significant difference in median velocity was found between healthy thyroid tissue and benign thyroid nodules, a significant difference was found between malignant thyroid nodules on the one hand and healthy thyroid tissue (p = 0.0019) or benign thyroid nodules (p = 0.0039) on the other hand. No significant difference of diagnostic accuracy for the diagnosis of malignant thyroid nodules was found between RTE and ARFI-imaging (0.74 vs. 0.69, p = 0.54). The combination of RTE with ARFI did not improve diagnostic accuracy. Conclusions: ARFI can be used as an additional tool in the diagnostic work up of thyroid nodules with high negative predictive value and comparable results to RTE

Establishment of routine sample preparation protocols at the newly installed MICADAS 14C dating facility at AWI

In November 2016, the first Mini-Carbon-Dating-System (MICADAS) manufactured by Ionplus AG was delivered and installed at the Alfred-Wegener-Institute (AWI), Germany. The new facility includes a graphitization unit (AGE3) connected with an elementar analyser (EA), a carbonate handling system (CHS), and a gas inlet system (GIS). The main goal for the facility at AWI will be the precise and independent dating of carbonaceous materials in marine sediments, sea-ice, and water to address various processes of the global carbon cycling. A particular focus will be on sediments from the high latitude oceans, in which radiocarbon-based age models are often difficult to obtain due to the scarcity of carbonate microfossils. One advantage of the MICADAS is the potential to analyse samples, which contain only a small amount of carbon as CO2 gas. For example, it will be possible to determine 14C ages of samples of foraminifera from carbonate-lean sediments, allowing for paleoclimate reconstructions in key locations for Earth’s climate system such as the Southern ocean. Likewise, compound-specific 14C analyses receive growing attention in carbon cycle studies and require handling of small samples of typically <100µg carbon. The wide range of applications encompassing gas analyses of foraminifera and compound-specific analysis as well as analyses of graphite targets requires establishing routine protocols of various methods of sample preparation, as well as thorough assessment of the respective carbon blanks. We report on our standard procedures for samples of organic matter from sediments or water including carbonate removal, combustion and graphitization using the AGE3 coupled to the EA, as well as on the methodology applied for carbonate samples using the CHS system and the GIS. We have investigated different sample preparation protocols and present the initial results using materials of known age. Additionally, we present the first results of our assessment of process blanks

Insulin gene polymorphisms in type I diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

Background: Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from ß-cell autoimmunity. Methods: We investigated the role of the -2221Msp(C/T) and -23HphI(A/T) polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317), Addison´s disease (AD, n = 107) or Hashimoto´s thyroiditis (HT, n = 61)], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62) as well as in healthy controls (HC, n = 275). Results: T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T) and "AA" -23HphI(A/T) polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively). The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion: We demonstrate that the allele "C" of the -2221Msp(C/T) and "A" -23HphI(A/T) insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II

Designing an optimal HIV programme for South Africa: Does the optimal package change when diminishing returns are considered?

Abstract Background South Africa has a large domestically funded HIV programme with highly saturated coverage levels for most prevention and treatment interventions. To further optimise its allocative efficiency, we designed a novel optimisation method and examined whether the optimal package of interventions changes when interaction and non-linear scale-up effects are incorporated into cost-effectiveness analysis. Methods The conventional league table method in cost-effectiveness analysis relies on the assumption of independence between interventions. We added methodology that allowed the simultaneous consideration of a large number of HIV interventions and their potentially diminishing marginal returns to scale. We analysed the incremental cost effectiveness ratio (ICER) of 16 HIV interventions based on a well-calibrated epidemiological model that accounted for interaction and non-linear scale-up effects, a custom cost model, and an optimisation routine that iteratively added the most cost-effective intervention onto a rolling baseline before evaluating all remaining options. We compared our results with those based on a league table. Results The rank order of interventions did not differ substantially between the two methods- in each, increasing condom availability and male medical circumcision were found to be most cost-effective, followed by anti-retroviral therapy at current guidelines. However, interventions were less cost-effective throughout when evaluated under the optimisation method, indicating substantial diminishing marginal returns, with ICERs being on average 437% higher under our optimisation routine. Conclusions Conventional league tables may exaggerate the cost-effectiveness of interventions when programmes are implemented at scale. Accounting for interaction and non-linear scale-up effects provides more realistic estimates in highly saturated real-world settings

Permafrost-carbon mobilization in Beringia caused by deglacial meltwater runoff, sea-level rise and warming

During the last deglaciation (18–8 kyr BP), shelf flooding and warming presumably led to a large-scale decomposition of permafrost soils in the mid-to-high latitudes of the Northern Hemisphere. Microbial degradation of old organic matter released from the decomposing permafrost potentially contributed to the deglacial rise in atmospheric CO2 and also to the declining atmospheric radiocarbon contents (Δ14C). The significance of permafrost for the atmospheric carbon pool is not well understood as the timing of the carbon activation is poorly constrained by proxy data. Here, we trace the mobilization of organic matter from permafrost in the Pacific sector of Beringia over the last 22 kyr using mass-accumulation rates and radiocarbon signatures of terrigenous biomarkers in four sediment cores from the Bering Sea and the Northwest Pacific. We find that pronounced reworking and thus the vulnerability of old organic carbon to remineralization commenced during the early deglaciation (~16.8 kyr BP) when meltwater runoff in the Yukon River intensified riverbank erosion of permafrost soils and fluvial discharge. Regional deglaciation in Alaska additionally mobilized significant fractions of fossil, petrogenic organic matter at this time. Permafrost decomposition across Beringia's Pacific sector occurred in two major pulses that match the Bølling-Allerød and Preboreal warm spells and rapidly initiated within centuries. The carbon mobilization likely resulted from massive shelf flooding during meltwater pulses 1A (~14.6 kyr BP) and 1B (~11.5 kyr BP) followed by permafrost thaw in the hinterland. Our findings emphasize that coastal erosion was a major control to rapidly mobilize permafrost carbon along Beringia's Pacific coast at ~14.6 and ~11.5 kyr BP implying that shelf flooding in Beringia may partly explain the centennial-scale rises in atmospheric CO2 at these times. Around 16.5 kyr BP, the mobilization of old terrigenous organic matter caused by meltwater-floods may have additionally contributed to increasing CO2 levels

Inpatient care costs of COVID-19 in South Africa’s public healthcare system

Background: Coronavirus disease 2019 (COVID-19) has had a devastating impact globally, with severe health and economic consequences. To prepare health systems to deal with the pandemic, epidemiological and cost projection models are required to inform budgets and efficient allocation of resources. This study estimates daily inpatient care costs of COVID-19 in South Africa, an important input into cost projection and economic evaluation models. Methods: We adopted a micro-costing approach, which involved the identification, measurement and valuation of resources used in the clinical management of COVID-19. We considered only direct medical costs for an episode of hospitalisation from the South African public health system perspective. Resource quantities and unit costs were obtained from various sources. Inpatient costs per patient day was estimated for consumables, capital equipment and human resources for three levels of inpatient care – general wards, high care wards and intensive care units (ICUs). Results: Average daily costs per patient increased with the level of care. The highest average daily cost was estimated for ICU admissions – 271 USD to 306 USD (financial costs) and ~800 USD to 830 USD (economic costs, excluding facility fee) depending on the need for invasive vs. non-invasive ventilation (NIV). Conversely, the lowest cost was estimated for general ward-based care – 62 USD to 79 USD (financial costs) and 119 USD to 278 USD (economic costs, excluding facility fees) depending on the need for supplemental oxygen. In high care wards, total cost was estimated at 156 USD, financial costs and 277 USD, economic costs (excluding facility fees). Probabilistic sensitivity analyses suggest our costs estimates are robust to uncertainty in cost inputs. Conclusion: Our estimates of inpatient costs are useful for informing budgeting and planning processes and costeffectiveness analysis in the South African context. However, these estimates can be adapted to inform policy decisions in other context