growing political momentum to definitively address tuberculosis, could all make ending the pandemic within a generation more feasible than ever before. Moving forward with bold, comprehensive strategies Globally, the priority must be to deliver person-centred and family-centred services to all individuals with tuberculosis who present to care. This approach means ensuring that high-quality diagnostics, treatment, and prevention modalities are available to all, wherever they seek care. Improving quality of tuberculosis care in the private sector is crucial to end tuberculosis in high incidence countries such as India, the country with the highest tuberculosis burden. Modelling shows that optimising private sector engagement in India could avert 8 million deaths from tuberculosis between 2019 and 2045 (appendix p 3). In high drug-resistant tuberculosis burden countries, access to rapid drug susceptibility testing (DST) and second-line drugs is essential to success. In Moldova, where more than 25% of all tuberculosis cases are drug-resistant, improving access to DST and second-line drugs would reduce mortality from drug-resistant tuberculosis by 44% in the coming generation (appendix p 3). Secondly, tuberculosis programme budgets must increase to enable reaching these people and populations at high risk of tuberculosis. In Kenya, for example, where the proportions of HIV and tuberculosis coinfection are high, scaling up access to both antiretroviral therapy and tuberculosis preventive therapy can help save an additional 3 million lives over the next generation (appendix p 3). However, ultimately, the fight against tuberculosis will not be won unless countries also ensure that everyone, not just high-risk groups, can access essential health Key messages The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer the question of how countries with high-burden tuberculosis and their development partners should target their future investments to ensure that ending tuberculosis is achievable. Invest first to ensure that high quality rapid diagnostics and treatment are provided to all individuals receiving care for tuberculosis, wherever they seek care This priority includes rapid drug susceptibility testing and second-line treatment for resistant forms of tuberculosis. Achieving universal, high-quality person-centred and family-centred care-including sustained improvement in the performance of private sector providers-usually should be the top policy and budget priority. Reach people and populations at high risk for tuberculosis (such as household and other close contacts of people with tuberculosis, and people with HIV) and bring them into care Active case-finding and treatment in high-risk populations demands adequate resources to reach and care for these populations. At the same time, reaching certain high-risk populations, such as people co-infec...

For both vaccinated and unvaccinated women, age-based screening by use of HPV DNA testing as a triage test for equivocal results in younger women and as a primary screening test in older women is expected to be more cost-effective than current screening recommendations.

IMPORTANCE In rural India, as in many developing countries, childhood mortality remains high and the quality of health care available is low. Improving care in such settings, where most health care practitioners do not have formal training, requires an assessment of the practitioners’ knowledge of appropriate care and the actual care delivered (the know-do gap). OBJECTIVE To assess the knowledge of local health care practitioners and the quality of care provided by them for childhood diarrhea and pneumonia in rural Bihar, India. DESIGN, SETTING, AND PARTICIPANTS We conducted an observational, cross-sectional study of the knowledge and practice of 340 health care practitioners concerning the diagnosis and treatment of childhood diarrhea and pneumonia in Bihar, India, from June 29 through September 8, 2012. We used data from vignette interviews and unannounced standardized patients (SPs). MAIN OUTCOMES AND MEASURES For SPs and vignettes, practitioner performance was measured using the numbers of key diagnostic questions asked and examinations conducted. The know-do gap was calculated by comparing fractions of practitioners asking key diagnostic questions on each method. Multivariable regressions examined the relation among diagnostic performance, prescription of potentially harmful treatments, and the practitioners’ characteristics. We also examined correct treatment recommended by practitioners with both methods. RESULTS Practitioners asked a mean of 2.9 diagnostic questions and suggested a mean of 0.3 examinations in the diarrhea vignette; mean numbers were 1.4 and 0.8, respectively, for the pneumonia vignette. Although oral rehydration salts, the correct treatment for diarrhea, are commonly available, only 3.5% of practitioners offered them in the diarrhea vignette. With SPs, no practitioner offered the correct treatment for diarrhea, and 13.0% of practitioners offered the correct treatment for pneumonia. Diarrhea treatment has a large know-do gap; practitioners asked diagnostic questions more frequently in vignettes than for SPs. Although only 20.9% of practitioners prescribed treatments that were potentially harmful in the diarrhea vignettes, 71.9% offered them to SPs (P < .001). Unqualified practitioners were more likely to prescribe potentially harmful treatments for diarrhea (adjusted odds ratio, 5.11 [95% CI, 1.24–21.13]). Higher knowledge scores were associated with better performance for treating diarrhea but not pneumonia. CONCLUSIONS AND RELEVANCE Practitioners performed poorly with vignettes and SPs, with large know-do gaps, especially for childhood diarrhea. Efforts to improve health care for major causes of childhood mortality should emphasize strategies that encourage pediatric health care practitioners to diagnose and manage these conditions correctly through better monitoring and incentives in addition to practitioner training initiatives.

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Bill and Melinda Gates Foundation.

PURPOSE Two anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies are approved for diffuse large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel; each costs $373,000. We evaluated their cost effectiveness. METHODS We used a decision analytic Markov model informed by recent multicenter, single-arm trials to evaluate axi-cel and tisagenlecleucel in multiply relapsed/refractory, adult, diffuse large B-cell lymphoma from a US health payer perspective over a lifetime horizon. Under a range of plausible long-term effectiveness assumptions, each therapy was compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were undiscounted life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (3% annual discount rate). Sensitivity analyses explored uncertainty. RESULTS In an optimistic scenario, assuming a 40% 5-year progression-free survival (PFS), axi-cel increased life expectancy by 8.2 years at $129,000/QALY gained (95% uncertainty interval, $90,000 to $219,000). At a 30% 5-year PFS, improvements in life expectancy were more modest (6.4 years) and expensive ($159,000/QALY gained [95% uncertainty interval, $105,000 to $284,000]). In an optimistic scenario, assuming a 35% 5-year PFS, tisagenlecleucel increased life expectancy by 4.6 years at $168,000/QALY gained (95% uncertainty interval, $105,000 to $414,000/QALY). At a 25% 5-year PFS, improvements in life expectancy were smaller (3.4 years) and more expensive ($223,000/QALY gained [95% uncertainty interval, $123,000 to $1,170,000/QALY]). Administering CAR-T to all indicated patients would increase US health care costs by approximately $10 billion over 5 years. Price reductions to $250,000 and $200,000, respectively, or payment only for initial complete response (at current prices) would allow axi-cel and tisagenlecleucel to cost less than $150,000/QALY, even at 25% PFS. CONCLUSION At 2018 prices, it is possible that both CAR-T therapies meet a less than $150,000/QALY threshold. This depends on long-term outcomes compared with chemoimmunotherapy and stem-cell transplantation, which are uncertain. Widespread adoption would substantially increase non-Hodgkin lymphoma health care costs. Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes.

Purpose The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel was recently approved to treat relapsed or refractory pediatric acute lymphoblastic leukemia. With a one-time infusion cost of $475,000, tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to determine whether tisagenlecleucel is cost effective compared with currently available treatments. Methods Markov modeling was used to evaluate tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia from a US health payer perspective over a lifetime horizon. The model was informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel (under a range of plausible long-term effectiveness) was compared with blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic sensitivity analyses were used to explore uncertainty. Main outcomes were life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Results With an assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5-year relapse-free survival rate, life-expectancies were more modest (3.8 years) and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate and with use as a bridge to transplant, tisagenlecleucel increased life expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios. Conclusion The long-term effectiveness of tisagenlecleucel is a critical but uncertain determinant of its cost effectiveness. At its current price, tisagenlecleucel represents reasonable value if it can keep a substantial fraction of patients in remission without transplantation; however, if all patients ultimately require a transplantation to remain in remission, it will not be cost effective at generally accepted thresholds. Price reductions would favorably influence cost effectiveness even if long-term clinical outcomes are modest.

Background Although much of the public health effort to combat COVID-19 has focused on disease control strategies in public settings, transmission of SARS-CoV-2 within households remains an important problem. The nature and determinants of household transmission are poorly understood. Methods To address this gap, we gathered and analyzed data from 22 published and pre-published studies from 10 countries (20,291 household contacts) that were available through September 2, 2020. Our goal was to combine estimates of the SARS-CoV-2 household secondary attack rate (SAR) and explore variation in estimates of the household SAR. Results The overall pooled random-effects estimate of the household SAR was 17.1% (95% CI: 13.7-21.2%). In study-level, random-effects meta-regressions stratified by testing frequency (1 test, 2 tests, &gt;2 tests), SAR estimates were 9.2% (95% CI: 6.7-12.3%), 17.5% (95% CI: 13.9-21.8%), and 21.3% (95% CI: 13.8-31.3%), respectively. Household SAR tended to be higher among older adult contacts and among contacts of symptomatic cases. Conclusions These findings suggest that SAR reported using a single follow-up test may be underestimated and that testing household contacts of COVID-19 cases on multiple occasions may increase the yield for identifying secondary cases.