697 research outputs found
Meta‐analysis of the difference of medians
No full textWe consider the problem of meta-analyzing two-group studies that report the median of the outcome. Often, these studies are excluded from meta-analysis because there are no well-established statistical methods to pool the difference of medians. To include these studies in meta-analysis, several authors have recently proposed methods to estimate the sample mean and standard deviation from the median, sample size, and several commonly reported measures of spread. Researchers frequently apply these methods to estimate the difference of means and its variance for each primary study and pool the difference of means using inverse variance weighting. In this work, we develop several methods to directly meta-analyze the difference of medians. We conduct a simulation study evaluating the performance of the proposed median-based methods and the competing transformation-based methods. The simulation results show that the median-based methods outperform the transformation-based methods when meta-analyzing studies that report the median of the outcome, especially when the outcome is skewed. Moreover, we illustrate the various methods on a real-life data set.Y
TB diagnostics: current pipeline, new developments and unmet needs
No full textOne of the biggest barriers for TB control is the lack of tools and strategies to diagnose TB quickly and accurately, such that TB transmission can be reduced. In the past few years, the new diagnostics pipeline for TB has rapidly expanded, and there have been several new policies and guidelines on TB diagnostics. For active TB diagnosis and rapid diagnosis of drug resistance, the most important recent breakthrough has been the Xpert® MTB/RIF, a completely automated, cartridge-based molecular assay. Currently, efforts are underway to scale-up the Xpert MTB/RIF technology in high TB burden countries, but there are several barriers to scale-up, including high cost, limited laboratory capacity, widespread abuse of suboptimal and inaccurate tests and lack of adequate regulation in many high TB burden countries. Currently available serological (antibody-detection) tests for TB have failed and the WHO has issued a negative policy recommendation against their use. However, further research is needed to develop a simple, rapid, inexpensive point-of-care test for TB disease. Newer tests, the IFN-γ release assays, have recently emerged for LTBI diagnosis. These tests are highly specific and most helpful for latent TB infection screening in bacillus Calmette-Guérin (BCG)-vaccinated individuals, particularly in settings where BCG vaccination is administered after infancy or multiple BCG vaccinations are given. A growing number of studies show that both the IFN-γ release assays and tuberculin skin test have limited prognostic value. There is a need for a highly predictive biomarker or combination of biomarkers and risk factors that will allow accurate prediction of the subgroup of latently infected individuals that are at highest risk of progression to disease. Overall, major advances have been made in TB diagnostics product and policy development. However, products and policies by themselves do not guarantee scale-up or impact. The biggest challenge now is translation of policy into practice, to save lives and reduce TB incidence.N
Costing the implementation of public health interventions in resource-limited settings: a conceptual framework
No full textBackground: 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.Y
TB diagnostic tests: how do we figure out their costs?
No full textTuberculosis continues to be a major global health problem. Lack of accurate, rapid and cost-effective diagnostic tests poses a huge obstacle to global TB control. While several new diagnostic tools are being developed and evaluated for TB, it is important that new tools are introduced for widespread use only after careful validation of accuracy, impact as well as cost-effectiveness in real-world settings. While there are large numbers of studies on the accuracy of TB diagnostic tests, there are few studies that are focused on cost and cost-effectiveness. There are currently no widely accepted standards on how to evaluate costs of a TB test. In this review, we describe the basic approach for computing the costs of TB diagnostic tests, and provide templates for various data elements and parameters that go into the costing analysis. We hope this will pave the way for a standardized methodology for costing of TB diagnostic tests. Such a tool would enable improved and more generalizable costing analyses that can provide a strong foundation for more sophisticated economic analyses that evaluate the full economic and epidemiological impact resulting from the implementation and routine use of performance-verified new and innovative diagnostic tools. This, in turn, will facilitate evidence-based adoption and use of new diagnostics, especially in resource-limited settings.Y
Cost-effectiveness of Preventive Therapy for Tuberculosis With Isoniazid and Rifapentine Versus Isoniazid Alone in High-Burden Settings
No full textBackground. A short-course regimen of 3 months of weekly rifapentine and isoniazid (3HP) has recently been recommended by the World Health Organization as an alternative to at least 6 months of daily isoniazid (isoniazid preventive therapy [IPT]) for prevention of tuberculosis (TB). The contexts in which 3HP may be cost-effective compared to IPT among people living with human immunodeficiency virus are unknown. Methods. We used a Markov state transition model to estimate the incremental cost-effectiveness of 3HP relative to IPT in high-burden settings, using a cohort of 1000 patients in a Ugandan HIV clinic as an emblematic scenario. Cost-effectiveness was expressed as 2017 US dollars per disability-adjusted life year (DALY) averted from a healthcare perspective over a 20-year time horizon. We explored the conditions under which 3HP would be considered cost-effective relative to IPT. Results. Per 1000 individuals on antiretroviral therapy in the reference scenario, treatment with 3HP rather than IPT was estimated to avert 9 cases of TB and 1 death, costing 1000 per DALY averted, 3HP is likely to be cost-effective relative to IPT only if the price of rifapentine can be greatly reduced (to approximately $20 per course) and high treatment completion (85%) can be achieved. Conclusions. 3HP may be a cost-effective alternative to IPT in high-burden settings, but cost-effectiveness depends on the price of rifapentine, achievable completion rates, and local willingness to pay.Y
Determining cost and placement decisions for moderate complexity NAATs for tuberculosis drug susceptibility testing.
No full textBackgroundAccess to drug resistant testing for tuberculosis (TB) remains a challenge in high burden countries. Recently, the World Health Organization approved the use of several moderate complexity automated nucleic acid amplification tests (MC-NAAT) that have performance profiles suitable for placement in a range of TB laboratory tiers to improve drug susceptibility tests (DST) coverage.MethodsWe conducted cost analysis of two MC-NAATs with different testing throughput: Lower Throughput (LT, ResultsThe base-case per test cost of 13.79 - 15.37 (range: 37.40) for HT test. Per test cost estimates were most sensitive to the number of testing days per week, followed by equipment costs and TB-specific workloads. In general, HT NAATs were cheaper at all testing volume levels, but at lower testing volumes (less than 2,000 per year) LT tests can be cheaper if the durability of the testing system is markedly better and/or procured equipment costs are lower than that of HT NAAT.ConclusionAssuming equivalent performance and infrastructural needs, placement strategies for MC-NAATs need to be prioritized by laboratory system's operational factors, testing demands, and costs
Healthcare use and medical cost before and after diagnosis of nontuberculous mycobacterial infection in Korea: the National Health Insurance Service-National Sample Cohort Study
No full textBackground and objective: The global prevalence and incidence of nontuberculous mycobacterial (NTM) infections are increasing; however, population-level data on healthcare use and medical costs for people with NTM infections are limited. Thus, we investigated the rates of healthcare use and medical costs of people with NTM infections in South Korea using the National Health Insurance Service-National Sample Cohort from 2002 to 2015. Methods: In this cohort study, people with and without NTM infection aged 20–89 years were matched 1 to 4 by sex, age, Charlson comorbidity index, and year of diagnosis. The overall and annual average healthcare use and medical costs were calculated. In addition, trends in healthcare use and medical costs for each of the 3 years before and after NTM diagnosis were investigated for people diagnosed with NTM infection. Results: A total of 798 individuals (336 men and 462 women) diagnosed with NTM infection and 3192 controls were included in the study. NTM-infected patients had significantly higher rates of healthcare use and medical costs than those in the control group ( p < 0.05). NTM-infected patients showed 1.5 times the medical cost and 4.5 times the respiratory disease cost of the control group. People diagnosed with NTM infection incurred the highest medical costs in the 6 months before diagnosis. Conclusion: NTM infection increases the economic burden on Korean adults. Appropriate diagnostic tests and treatment plans for NTM infections are needed to reduce the burden of the disease caused by such infection
Epidemiological Characteristics of Nontuberculous Mycobacterial Pulmonary Disease in South Korea: A Meta-analysis of Individual Participant Data
No full textBackground: Despite the global increase in nontuberculous mycobacterial pulmonary disease (NTM-PD), clinical characteristics show geographical variations. We investigated the clinical characteristics of patients with NTM-PD in South Korea. Methods: We systematically reviewed articles concerning patients with NTM-PD in South Korea until February 2022. Individual participant data, regardless of treatment, were collected using a standard case report form. Results: Data of 6,489 patients from 11 hospitals between 2002 and 2019 were analyzed. The mean age was 61.5 +/- 11.7 years, of whom 57.7% were women. Mycobacterium avium (41.4%) and Mycobacterium intracellulare (38.4%) comprised most of the causative species, followed by Mycobacterium abscessus subspecies abscessus (8.6%) and M. abscessus subspecies massiliense (7.8%). Bronchiectasis (59.4%) was the most common pulmonary comorbidity. Although reported cases of NTM-PD increased over the years, the proportions of causative species and radiologic forms remained similar. Distinct clinical characteristics were observed according to age and sex. Men were older at the time of diagnosis (median 63.8 years vs. 59.9 years, p<0.001), and had more cavitary lesions than women (38.8% vs. 21.0%, p<0.001). The older group (>= 65 years) had higher proportions of patients with body mass index <18.5 kg/m 2 (27.4% vs. 18.6%, p<0.001) and cavitary lesions (29.9% vs. 27.6%, p=0.009) than the younger group. Conclusion: We conducted a meta -analysis of the clinical characteristics of patients with NTM-PD in South Korea, and found age- and sex -related differences in disease -specific severity. Further investigation would enhance our comprehension of the nature of the disease, and inherited and acquired host factors.Y
EXPLORING THE EPIDEMIOLOGICAL IMPACT OF UNIVERSAL ACCESS TO RAPID TUBERCULOSIS DIAGNOSIS USING AGENT-BASED SIMULATION
No full textMany high-burden countries have committed to providing universal access to rapid diagnosis of tuberculosis (TB), but the corresponding impact on population-wide incidence is unknown. We designed an agent-based simulation of drug-susceptible (DS) and drug-resistant (DR) TB in a representative Indian setting and compared the impact of Xpert testing via a decentralized (Xpert available at each local-population) versus centralized (Xpert available at the district-level serving multiple local-populations) strategy. Decentralized testing resulted in a 36% reduction in DR-TB incidence at 10 years compared to no Xpert. Depending on assumptions regarding pre-treatment loss to follow-up (ranging from 5 to 50%), the impact of centralized testing ranged from a 35% to 22% reduction in DR-TB incidence. Implementation of Xpert by either approach had a negligible impact (<5%) on DS-TB incidence. Decisions regarding choice of centralized vs. decentralized Xpert will heavily depend on operational aspects of centralized Xpert and loss to follow-up.N
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