Vaccine value profile for Klebsiella pneumoniae.

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91-1.71) and 4.95 million (95% UI: 3.62-6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K.pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K.pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public-private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K.pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Attributed causes of excess mortality during the COVID-19 pandemic in a south Indian city.

Globally, excess deaths during 2020-21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 deaths from other changes in mortality related to pandemic control measures using medically-certified death registrations from Madurai, India-an urban center with well-functioning vital surveillance. Between March, 2020 and July, 2021, all-cause deaths in Madurai exceeded expected levels by 30% (95% confidence interval: 27-33%). Although driven by deaths attributed to cardiovascular or cerebrovascular conditions, diabetes, senility, and other uncategorized causes, increases in these attributions were restricted to medically-unsupervised deaths, and aligned with surges in confirmed or attributed COVID-19 mortality, likely reflecting mortality among unconfirmed COVID-19 cases. Implementation of lockdown measures was associated with a 7% (0-13%) reduction in all-cause mortality, driven by reductions in deaths attributed to injuries, infectious diseases and maternal conditions, and cirrhosis and other liver conditions, respectively, but offset by a doubling in cancer deaths. Our findings help to account for gaps between documented COVID-19 mortality and excess all-cause mortality during the pandemic in an LMIC setting.

Antimicrobial Resistance: Is Health Technology Assessment Part of the Solution or Part of the Problem?

Antimicrobial resistance is a serious challenge to the success and sustainability of our healthcare systems. There has been increasing policy attention given to antimicrobial resistance in the last few years, and increased amounts of funding have been channeled into funding for research and development of antimicrobial agents. Nevertheless, manufacturers doubt whether there will be a market for new antimicrobial technologies sufficient to enable them to recoup their investment. Health technology assessment (HTA) has a critical role in creating confidence that if valuable technologies can be developed they will be reimbursed at a level that captures their true value. We identify 3 deficiencies of current HTA processes for appraising antimicrobial agents: a methods-centric approach rather than problem-centric approach for dealing with new challenges, a lack of tools for thinking about changing patterns of infection, and the absence of an approach to epidemiological risks. We argue that, to play their role more effectively, HTA agencies need to broaden their methodological tool kit, design and communicate their analysis to a wider set of users, and incorporate long-term policy goals, such as containing resistance, as part of their evaluation criteria alongside immediate health gains.

SARS-CoV-2 infection and mortality during the first epidemic wave in Madurai, south India: a prospective, active surveillance study.

BACKGROUND: SARS-CoV-2 has spread substantially within India over multiple waves of the ongoing COVID-19 pandemic. However, the risk factors and disease burden associated with COVID-19 in India remain poorly understood. We aimed to assess predictors of infection and mortality within an active surveillance study, and to probe the completeness of case and mortality surveillance. METHODS: In this prospective, active surveillance study, we used data collected under expanded programmatic surveillance testing for SARS-CoV-2 in the district of Madurai, Tamil Nadu, India (population of 3 266 000 individuals). Prospective testing via RT-PCR was done in individuals with fever or acute respiratory symptoms as well as returning travellers, frontline workers, contacts of laboratory-confirmed COVID-19 cases, residents of containment zones, patients undergoing medical procedures, and other risk groups. Standardised data collection on symptoms and chronic comorbid conditions was done as part of routine intake. Additionally, seroprevalence of anti-SARS-CoV-2 immunoglobulin G was assessed via a cross-sectional survey recruiting adults across 38 clusters within Madurai District from Oct 19, 2020, to Nov 5, 2020. We estimated adjusted odds ratios (aORs) for positive RT-PCR results comparing individuals by age, sex, comorbid conditions, and aspects of clinical presentation. We estimated case-fatality ratios (CFRs) over the 30-day period following RT-PCR testing stratified by the same variables, and adjusted hazard ratios (aHRs) for death associated with age, sex, and comorbidity. We estimated infection-fatality ratios (IFRs) on the basis of age-specific seroprevalence. RESULTS: Between May 20, 2020, and Oct 31, 2020, 13·5 diagnostic tests were done per 100 inhabitants within Madurai, as compared to 7·9 tests per 100 inhabitants throughout India. From a total of 440 253 RT-PCR tests, 15 781 (3·6%) SARS-CoV-2 infections were identified, with 8720 (5·4%) of 160 273 being positive among individuals with symptoms, and 7061 (2·5%) of 279 980 being positive among individuals without symptoms, at the time of presentation. Estimated aORs for symptomatic RT-PCR-confirmed infection increased continuously by a factor of 4·3 from ages 0-4 years to 80 years or older. By contrast, risk of asymptomatic RT-PCR-confirmed infection did not differ across ages 0-44 years, and thereafter increased by a factor of 1·6 between ages 45-49 years and 80 years or older. Seroprevalence was 40·1% (95% CI 35·8-44·6) at age 15 years or older by the end of the study period, indicating that RT-PCR clinical testing and surveillance testing identified only 1·4% (1·3-1·6%) of all infections in this age group. Among RT-PCR-confirmed cases, older age, male sex, and history of cancer, diabetes, other endocrine disorders, hypertension, other chronic circulatory disorders, respiratory disorders, and chronic kidney disease were each associated with elevated risk of mortality. The CFR among RT-PCR-confirmed cases was 2·4% (2·2-2·6); after age standardisation. At age 15 years or older, the IFR based on reported deaths was 0·043% (0·039-0·049), with reported deaths being only 11·0% (8·2-14·5) of the expected count. INTERPRETATION: In a large-scale SARS-CoV-2 surveillance programme in Madurai, India, we identified equal risk of asymptomatic infection among children, teenagers, and working-age adults, and increasing risk of infection and death associated with older age and comorbidities. Establishing whether surveillance practices or differences in infection severity account for gaps between observed and expected mortality is of crucial importance to establishing the burden of COVID-19 in India. FUNDING: The Bill & Melinda Gates Foundation, the National Science Foundation, and the National Institute of General Medical Sciences. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Incidence and etiology of clinically-attended, antibiotic-treated diarrhea among children under five years of age in low- and middle-income countries: Evidence from the Global Enteric Multicenter Study.

Diarrhea is a leading cause of antibiotic consumption among children in low- and middle-income countries. While vaccines may prevent diarrhea infections for which children often receive antibiotics, the contribution of individual enteropathogens to antibiotic use is minimally understood. We used data from the Global Enteric Multicenter Study (GEMS) to estimate pathogen-specific incidence of antibiotic-treated diarrhea among children under five years old residing in six countries of sub-Saharan Africa and South Asia before rotavirus vaccine implementation. GEMS was an age-stratified, individually-matched case-control study. Stool specimens were obtained from children presenting to sentinel health clinics with newly-onset, acute diarrhea (including moderate-to-severe and less-severe diarrhea) as well as matched community controls without diarrhea. We used data from conventional and quantitative molecular diagnostic assays applied to stool specimens to estimate the proportion of antibiotic-treated diarrhea cases attributable to each pathogen. Antibiotics were administered or prescribed to 9,606 of 12,109 moderate-to-severe cases and 1,844 of 3,174 less-severe cases. Across all sites, incidence rates of clinically-attended, antibiotic-treated diarrhea were 12.2 (95% confidence interval: 9.0-17.8), 10.2 (7.4-13.9) and 1.9 (1.3-3.0) episodes per 100 child-years at risk at ages 6 weeks to 11 months, 12-23 months, and 24-59 months, respectively. Based on the recommendation for antibiotic treatment to be reserved for cases with dysentery, we estimated a ratio of 12.6 (8.6-20.8) inappropriately-treated diarrhea cases for each appropriately-treated case. Rotavirus, adenovirus serotypes 40/41, Shigella, sapovirus, Shiga toxin-producing Escherichia coli, and Cryptosporidium were the leading antibiotic-treated diarrhea etiologies. Rotavirus caused 29.2% (24.5-35.2%) of antibiotic-treated cases, including the largest share in both the first and second years of life. Shigella caused 14.9% (11.4-18.9%) of antibiotic-treated cases, and was the leading etiology at ages 24-59 months. Our findings should inform the prioritization of vaccines with the greatest potential to reduce antibiotic exposure among children.

The potential global gains in health and revenue from increased taxation of tobacco, alcohol and sugar-sweetened beverages: a modelling analysis.

Introduction: Globally, a growing burden of morbidity and mortality is attributable to lifestyle behaviours, and in particular to the consumption of tobacco, alcohol and sugar-sweetened beverages (SSB). In low-income and middle-income countries, this increased disease burden falls on already encumbered and resource-constrained healthcare systems. Fiscal policies, specifically taxation, can lower consumption of tobacco, alcohol and SSB while raising government revenues. Methods: We simulated the health and economic effects of taxing cigarettes, alcohol and SSB over 50 years for 30-79 years old populations using separate mathematical models for each commodity that incorporated country-level epidemiological, demographic and consumption data. Based on data availability, national-level health effects of higher tobacco, alcohol and SSB taxes were simulated in 141, 166 and 176 countries, respectively, which represented 92%, 97% and 95% of the global population, respectively. Economic effects for tobacco, alcohol and SSB were estimated for countries representing 91%, 43% and 83% of the global population, respectively. These estimates were extrapolated to the global level by matching countries according to income level. Results: Over 50 years, taxes that raise the retail price of tobacco, alcoholic beverages and SSB by 20% could result in a global gain of 160.7 million (95% uncertainty interval (UI): 96.3 to 225.2 million), 227.4 million (UI: 161.2 to 293.6 million) and 24.3 million (UI: 15.7 to 35.4 million) additional life years, respectively. Conclusion: Excise tax increases on tobacco, alcohol and SSB can produce substantial health gains by reducing premature mortality while raising government revenues, which could be used to increase public health funding.

Is the efficacy of antibiotic prophylaxis for surgical procedures decreasing? Systematic review and meta-analysis of randomized control trials.

OBJECTIVE: Rising antibiotic resistance could reduce the effectiveness of antibiotics in preventing postoperative infections. We investigated trends in the efficacy of antibiotic prophylaxis regimens for 3 commonly performed surgical procedures-appendectomy, cesarean section, and colorectal surgery-and 1 invasive diagnostic procedure, transrectal prostate biopsy (TRPB). DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed and Cochrane databases (through October 31, 2017) for randomized control trials (RCTs) that measured the efficacy of antibiotic prophylaxis for 4 index procedures in preventing postoperative infections (surgical site infections [SSIs] following the 3 surgical procedures and a combination of urinary tract infections [UTIs] and sepsis following TRPB). RESULTS: Of 399 RCTs, 74 studies (9 appendectomy, 11 cesarean section, 39 colorectal surgery, and 15 TRPB) were included. Multilevel logistic regression models with random intercepts for each study showed no statistically significant increase in SSIs over time for appendectomy (adjusted odds ratio [aOR] per year, 1.03; 95% confidence interval [CI], 0.92-1.16; P=.57), cesarean section (aOR per year, 1.01; 95% CI, 0.96-1.05; P=.80), and TRPB (aOR per year, 0.95; 95% CI, 0.77-1.18; P=.67). However, there was a significant increase in SSIs proportion following colorectal surgery (aOR per year, 1.049; 95% CI, 1.03-1.07; P<.001). CONCLUSION: The efficacy of antibiotic prophylaxis agents in preventing SSIs following colorectal surgery has declined. Small number of RCTs and low infections rates limited our ability to assess true effect for simple appendectomy, cesarean section, or TRPB.

Simulating the impact of excise taxation for disease prevention in low-income and middle-income countries: an application to South Africa.

INTRODUCTION: Excise taxes are policy tools that have been applied internationally with some success to reduce consumption of products adversely impacting population health including tobacco, alcohol and increasingly junk foods and sugary beverages. As in other low-income and middle-income countries, South Africa faces a growing burden of lifestyle diseases; accordingly we simulate the impact of multiple excise tax interventions in this setting. METHODS: We construct a mathematical model to simulate the health and revenue effects of increased excise taxes, which is adaptable to a variety of settings given its limited data requirements. Applying the model to South Africa, we simulate the impact of increased tax rates on tobacco and beer and of the introduction of a tax on sugar-sweetened beverages (SSB). Drawing on surveys of product usage and risk factor prevalence, the model uses a potential impact fraction to simulate the health effects of tax interventions. RESULTS: Adopting an excise rate of 60% on tobacco would result in a gain of 858 923 life-years (95% uncertainty interval (UI) 480 188 to 1 310 329), while adopting an excise rate of 25% on beer would result in a gain of 568 063 life-years (95% UI 412 110 to 775 560) and the adoption of a 20% tax on SSBs would result in a gain of 688 719 life-years (95% UI 321 788 to 1 079 653). CONCLUSION: More aggressive excise tax policies on tobacco, beer and SSBs in South Africa could result in meaningful improvements in population health and raised revenue.

Universal health coverage and intersectoral action for health: key messages from Disease Control Priorities, 3rd edition.

The World Bank is publishing nine volumes of Disease Control Priorities, 3rd edition (DCP3) between 2015 and 2018. Volume 9, Improving Health and Reducing Poverty, summarises the main messages from all the volumes and contains cross-cutting analyses. This Review draws on all nine volumes to convey conclusions. The analysis in DCP3 is built around 21 essential packages that were developed in the nine volumes. Each essential package addresses the concerns of a major professional community (eg, child health or surgery) and contains a mix of intersectoral policies and health-sector interventions. 71 intersectoral prevention policies were identified in total, 29 of which are priorities for early introduction. Interventions within the health sector were grouped onto five platforms (population based, community level, health centre, first-level hospital, and referral hospital). DCP3 defines a model concept of essential universal health coverage (EUHC) with 218 interventions that provides a starting point for country-specific analysis of priorities. Assuming steady-state implementation by 2030, EUHC in lower-middle-income countries would reduce premature deaths by an estimated 4·2 million per year. Estimated total costs prove substantial: about 9·1% of (current) gross national income (GNI) in low-income countries and 5·2% of GNI in lower-middle-income countries. Financing provision of continuing intervention against chronic conditions accounts for about half of estimated incremental costs. For lower-middle-income countries, the mortality reduction from implementing the EUHC can only reach about half the mortality reduction in non-communicable diseases called for by the Sustainable Development Goals. Full achievement will require increased investment or sustained intersectoral action, and actions by finance ministries to tax smoking and polluting emissions and to reduce or eliminate (often large) subsidies on fossil fuels appear of central importance. DCP3 is intended to be a model starting point for analyses at the country level, but country-specific cost structures, epidemiological needs, and national priorities will generally lead to definitions of EUHC that differ from country to country and from the model in this Review. DCP3 is particularly relevant as achievement of EUHC relies increasingly on greater domestic finance, with global developmental assistance in health focusing more on global public goods. In addition to assessing effects on mortality, DCP3 looked at outcomes of EUHC not encompassed by the disability-adjusted life-year metric and related cost-effectiveness analyses. The other objectives included financial protection (potentially better provided upstream by keeping people out of the hospital rather than downstream by paying their hospital bills for them), stillbirths averted, palliative care, contraception, and child physical and intellectual growth. The first 1000 days after conception are highly important for child development, but the next 7000 days are likewise important and often neglected.

Breastfeeding Duration and Adolescent Educational Outcomes: Longitudinal Evidence From India.

OBJECTIVE: There is a significant evidence gap on the long-term educational benefits of longer breastfeeding in low- and middle-income countries. We estimated the association between duration of (any) breastfeeding and educational outcomes of Indian children. METHODS: We used regression analysis to examine the association between the length of breastfeeding (in months) and future education outcomes on the basis of 2 data sets: (1) data from a follow-up survey known as the Andhra Pradesh Children and Parents Study (APCAPS, 2003-2005) of 1165 children aged 13 to 18 years from a controlled nutrition trial originally conducted in South India during the period of 1987 to 1990; and (2) nationally representative data from the India Human Development Survey (IHDS-2, 2011-2012) of 6121 children aged 6 to 12 years. RESULTS: In APCAPS, children with >36 months of breastfeeding scored 0.28 (95% confidence interval [95% CI]: 0.00-0.56; P < .05) higher on tests than those with up to 12 months of breastfeeding. In the nationally representative IHDS-2 data, above-median breastfeeding duration was associated with 0.1 year (95% CI: 0.04-0.16; P < .01) higher educational attainment. In IHDS-2, >12 to 24 months and >24 months of breastfeeding were associated with 0.12 (95% CI: 0.01-0.23; P < .05) and 0.19 years of (95% CI: 0.05-0.34; P < .05) higher educational attainment, respectively, than for those with up to 6 months of breastfeeding. In additional analyses by sex, we found that the benefits of breastfeeding accrued primarily to boys. CONCLUSION: Breastfeeding duration was associated with small gains in educational outcomes for boys but not for girls in India.

Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa in Children, United States, 1999-2012.

BACKGROUND: Pseudomonas aeruginosa is a common cause of healthcare-associated infection. Multidrug-resistant (MDR) (>3 classes) and carbapenem-resistant (CR) P aeruginosa are significant threats globally. We used a large reference-laboratory database to study the epidemiology of P aeruginosa in children in the United States. METHODS: Antimicrobial susceptibility data from the Surveillance Network were used to phenotypically identify MDR and CR P aeruginosa isolates in children aged 1 to 17 years between January 1999 and July 2012. Logistic regression analysis was used to calculate trends in the prevalence of MDR and CR P aeruginosa. Isolates from infants (<1 year old) and patients with cystic fibrosis were excluded. RESULTS: Among the isolates tested, the crude proportion of MDR P aeruginosa increased from 15.4% in 1999 to 26% in 2012, and the proportion of CR P aeruginosa increased from 9.4% in 1999 to 20% in 2012. The proportion of both MDR and CR P aeruginosa increased each year by 4% (odds ratio [OR], 1.04 [95% confidence interval (CI), 1.03-1.04] and 1.04 [95% CI, 1.04-1.05], respectively). In multivariable analysis, both MDR and CR P aeruginosa were more common in the intensive care setting, among children aged 13 to 17 years, in respiratory specimens, and in the West North Central region. In addition, resistance to other antibiotic classes (aminoglycosides, fluoroquinolones, cephalosporins, and piperacillin-tazobactam) often used to treat P aeruginosa increased. CONCLUSIONS: Rates of MDR and CR P aeruginosa infection in children are rising nationally. Aggressive prevention strategies, including instituting antimicrobial stewardship programs in pediatric settings, are essential for combating antimicrobial resistance.

Health and economic benefits of public financing of epilepsy treatment in India: An agent-based simulation model.

OBJECTIVE: An estimated 6-10 million people in India live with active epilepsy, and less than half are treated. We analyze the health and economic benefits of three scenarios of publicly financed national epilepsy programs that provide: (1) first-line antiepilepsy drugs (AEDs), (2) first- and second-line AEDs, and (3) first- and second-line AEDs and surgery. METHODS: We model the prevalence and distribution of epilepsy in India using IndiaSim, an agent-based, simulation model of the Indian population. Agents in the model are disease-free or in one of three disease states: untreated with seizures, treated with seizures, and treated without seizures. Outcome measures include the proportion of the population that has epilepsy and is untreated, disability-adjusted life years (DALYs) averted, and cost per DALY averted. Economic benefit measures estimated include out-of-pocket (OOP) expenditure averted and money-metric value of insurance. RESULTS: All three scenarios represent a cost-effective use of resources and would avert 800,000-1 million DALYs per year in India relative to the current scenario. However, especially in poor regions and populations, scenario 1 (which publicly finances only first-line therapy) does not decrease the OOP expenditure or provide financial risk protection if we include care-seeking costs. The OOP expenditure averted increases from scenarios 1 through 3, and the money-metric value of insurance follows a similar trend between scenarios and typically decreases with wealth. In the first 10 years of scenarios 2 and 3, households avert on average over US$80 million per year in medical expenditure. SIGNIFICANCE: Expanding and publicly financing epilepsy treatment in India averts substantial disease burden. A universal public finance policy that covers only first-line AEDs may not provide significant financial risk protection. Covering costs for both first- and second-line therapy and other medical costs alleviates the financial burden from epilepsy and is cost-effective across wealth quintiles and in all Indian states.

Cost Per DALY Averted in a Surgical Unit of a Private Hospital in India.

BACKGROUNDS: Cost-effectiveness analysis plays an important role to guide resource allocation decisions, however, information on cost per disability-adjusted life year (DALY) averted by health facilities is not available in many developing economies, including India. We estimated cost per DALY averted for 2611 patients admitted for surgical interventions in a 106-bed private for-profit hospital in northern India. METHODS: Costs were calculated using standard costing methods for the financial year 2012-2013, and effectiveness was measured in DALYs averted using risk of death/disability, effectiveness of treatment and disability weights from 2010 global burden of disease study. RESULTS: During the study period, total operating cost of the hospital for treating surgical patients was USD 1,554,406 and the hospital averted 9401 DALYs resulting in a cost per DALY averted of USD 165. CONCLUSIONS: Even though this study was based on one hospital in India, however, the hospital is a private hospital which is expected to have less surgical case load compared to government health facilities, cost per DALY averted for the surgical interventions is much lower than the cost-effectiveness threshold for India (USD 1508 in 2012). This study therefore provides evidence to re-think the common notion that surgical care is expensive and therefore of lower value than other health interventions.

Access to effective antimicrobials: a worldwide challenge.

Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.

Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study.

BACKGROUND: The declining efficacy of existing antibiotics potentially jeopardises outcomes in patients undergoing medical procedures. We investigated the potential consequences of increases in antibiotic resistance on the ten most common surgical procedures and immunosuppressing cancer chemotherapies that rely on antibiotic prophylaxis in the USA. METHODS: We searched the published scientific literature and identified meta-analyses and reviews of randomised controlled trials or quasi-randomised controlled trials (allocation done on the basis of a pseudo-random sequence-eg, odd/even hospital number or date of birth, alternation) to estimate the efficacy of antibiotic prophylaxis in preventing infections and infection-related deaths after surgical procedures and immunosuppressing cancer chemotherapy. We varied the identified effect sizes under different scenarios of reduction in the efficacy of antibiotic prophylaxis (10%, 30%, 70%, and 100% reductions) and estimated the additional number of infections and infection-related deaths per year in the USA for each scenario. We estimated the percentage of pathogens causing infections after these procedures that are resistant to standard prophylactic antibiotics in the USA. FINDINGS: We estimate that between 38·7% and 50·9% of pathogens causing surgical site infections and 26·8% of pathogens causing infections after chemotherapy are resistant to standard prophylactic antibiotics in the USA. A 30% reduction in the efficacy of antibiotic prophylaxis for these procedures would result in 120,000 additional surgical site infections and infections after chemotherapy per year in the USA (ranging from 40,000 for a 10% reduction in efficacy to 280,000 for a 70% reduction in efficacy), and 6300 infection-related deaths (range: 2100 for a 10% reduction in efficacy, to 15,000 for a 70% reduction). We estimated that every year, 13,120 infections (42%) after prostate biopsy are attributable to resistance to fluoroquinolones in the USA. INTERPRETATION: Increasing antibiotic resistance potentially threatens the safety and efficacy of surgical procedures and immunosuppressing chemotherapy. More data are needed to establish how antibiotic prophylaxis recommendations should be modified in the context of increasing rates of resistance. FUNDING: DRIVE-AB Consortium.

Quantifying uncertainty in intervention effectiveness with structured expert judgement: an application to obstetric fistula.

OBJECTIVE: To demonstrate a new application of structured expert judgement to assess the effectiveness of surgery to correct obstetric fistula in a low-income setting. Intervention effectiveness is a major input of evidence-informed priority setting in healthcare, but information on intervention effectiveness is generally lacking. This is particularly problematic in the context of poorly resourced healthcare settings where even efficacious interventions fail to translate into improvements in health. The few intervention effectiveness studies related to obstetric fistula treatment focus on the experience of single facilities and do not consider the impact of multiple factors that may affect health outcomes. DESIGN: We use the classical model of structured expert judgement, a method that has been used to quantify uncertainty in the areas of engineering and environmental risk assessment when data are unavailable. Under this method, experts quantify their uncertainty about rates of long-term disability in patients with fistula following treatment in different contexts, but the information content drawn from their responses is statistically conditioned on the accuracy and informativeness of their responses to a set of calibration questions. Through this method, we develop best estimates and uncertainty bounds for the rate of disability associated with each treatment scenario and setting. PARTICIPANTS: Eight experts in obstetric fistula repair in low and middle income countries. RESULTS: Estimates developed using performance weights were statistically superior to those involving a simple averaging of expert responses. The performance-weight decision maker's assessments are narrower for 9 of the 10 calibration questions and 21 of 23 variables of interest. CONCLUSIONS: We find that structured expert judgement is a viable approach to investigating the effectiveness of medical interventions where randomised controlled trials are not possible. Understanding the effectiveness of surgery performed at different types of facilities can guide programme planning to increase access to fistula treatment.

Early Childhood Nutrition Is Positively Associated with Adolescent Educational Outcomes: Evidence from the Andhra Pradesh Child and Parents Study (APCAPS).

BACKGROUND: India's Integrated Child Development Scheme, which provides supplementary nutrition and other public health services to >91 million women and children aged <6 y, is the largest program of its kind in the world. OBJECTIVE: We estimated the long-term associations of maternal and early childhood nutrition provided under the Integrated Child Development Scheme with educational outcomes when the children became adolescents. METHODS: We used longitudinal data from a controlled nutrition trial conducted near the city of Hyderabad, India. From 1987 to 1990, a balanced protein-energy supplement (corn-soya meal, called upma) was offered to pregnant women and children aged <6 y in 15 intervention villages, whereas no supplementation was offered in 14 control villages. Both groups had equal access to other public programs such as immunization and anemia control in pregnancy. Children born during the original trial period were resurveyed (654 intervention and 511 control group children) in 2003-2005. We used propensity score matching methods to correct for estimation bias in our regression models to assess the associations of supplementary nutrition with school enrollment, schooling grades completed, and academic test performance of these adolescents. RESULTS: Children born in intervention villages were 7.8% (95% CI: 0.1%, 15.4%; P < 0.05) more likely to be enrolled in school and completed 0.84 (95% CI: 0.28, 1.39; P < 0.005) more schooling grades than children born in control villages. We found no association between supplementary nutrition and academic performance, as measured by school test scores. CONCLUSION: Offering a nutritional supplement to pregnant women and children <6 y of age during the Hyderabad Nutrition Trial was associated with improved school enrollment and completion of more schooling grades when the children became adolescents.

Universal public finance of tuberculosis treatment in India: an extended cost-effectiveness analysis.

Universal public finance (UPF)-government financing of an intervention irrespective of who is receiving it-for a health intervention entails consequences in multiple domains. First, UPF increases intervention uptake and hence the extent of consequent health gains. Second, UPF generates financial consequences including the crowding out of private expenditures. Finally, UPF provides insurance either by covering catastrophic expenditures, which would otherwise throw households into poverty or by preventing diseases that cause them. This paper develops a method-extended cost-effectiveness analysis (ECEA)-for evaluating the consequences of UPF in each of these domains. It then illustrates ECEA with an evaluation of UPF for tuberculosis treatment in India. Using plausible values for key parameters, our base case ECEA concludes that the health gains and insurance value of UPF would accrue primarily to the poor. Reductions in out-of-pocket expenditures are more uniformly distributed across income quintiles. A variant on our base case suggests that lowering costs of borrowing for the poor could potentially achieve some of the health gains of UPF, but at the cost of leaving the poor more deeply in debt.

Postgraduate education in nutrition in south Asia: a huge mismatch between investments and needs.

BACKGROUND: Despite decades of nutrition advocacy and programming, the nutrition situation in South Asian countries is alarming. We assume that modern training in nutrition at the post graduate level is an important contributor to building the capacity of individuals to think and act effectively when combating undernutrition. In this context, this paper presents a regional situation analysis of master's level academic initiatives in nutrition with a special focus on the type of programme we think is most likely to be helpful in addressing undernutrition at the population level: Public Health Nutrition (PHN). METHODS: This situational analysis of Masters in nutrition across South Asian countries viz. India, Pakistan, Bangladesh, Sri Lanka, Afghanistan, Maldives, Nepal, Bhutan was conducted using an intensive and systematic Internet search. Further, detailed information was extracted from the individual institute websites and library visits. RESULTS: Of the 131 master's degree programmes we identified one that was in PHN while another 15 had modules in PHN. Most of these universities and institutions were found in India with a few in Bangladesh and Sri Lanka. In the rest of the countries, neither nutrition nor PHN emerged as an academic discipline at the master's level. In terms of eligibility Indian and Sri Lankan programmes were most inclusive, with the remaining countries restricting eligibility to those with health qualifications. On modules, no country had any on nutrition policy or on nutrition's interactions with agriculture, social protection, water and sanitation or women's empowerment. CONCLUSION: If a strong focus on public health nutrition is key to reducing undernutrition, then the poor availability of such courses in the region is cause for concern. Nutrition master's courses in general focus too little on the kinds of strategies highlighted in the recent Lancet series on nutrition. Governments seeking to accelerate declines in undernutrition should incentivize the delivery of postgraduate programmes in nutrition and Public Health Nutrition (PHN) that reflect the modern consensus on priority actions. In the absence of PHN type programmes, the competence to scale up nutrition capacity is likely to be impaired and the human potential of millions of infants will continue to be squandered.

Cost-effectiveness of treatment and secondary prevention of acute myocardial infarction in India: a modeling study.

BACKGROUND: Cardiovascular diseases are the single largest cause of death in India, with acute myocardial infarction (AMI) accounting for one-third of all heart disease deaths. Although effective treatment is available for AMI, access to treatment is dictated by cost and ability to pay. With scarce treatment resources, healthcare decisions are guided by local cost-effectiveness, for which country-level data are lacking. OBJECTIVES: We calculate the cost-effectiveness of policies that expand the use of aspirin, injection streptokinase, beta-blockers, angiotensin-converting enzyme inhibitors, and statins for the treatment and secondary prevention of AMI in India. We also estimate the cost-effectiveness of a hypothetical polypill (combining aspirin, beta blockers, angiotensin-converting enzyme inhibitors, and statins) for secondary prevention. METHODS: We conduct cost-effectiveness analyses of AMI treatment and secondary prevention for patients with previous coronary heart disease events in India. We estimate coronary heart disease events using Framingham risk scores and disease prevalence using a cohort ordinary differential model. Other parameter estimates are from the literature. Polypill treatment is assumed to cost less than the additive cost of all 4 oral medications, but it is not assumed to increase adherence. We conduct a Latin hypercube sampling sensitivity analysis on the model parameters. RESULTS: Increasing coverage of AMI treatment with aspirin and streptokinase would be cost-effective and could avert approximately 335,000 (191,000 to 503,000) disability-adjusted life years among 30- to 69-year-olds in India. Secondary prevention with aspirin and beta-blockers at 80% coverage (and at lower rates) would be highly cost-effective, and the addition of angiotensin-converting enzyme inhibitors would also be cost-effective. Introducing the polypill dominates a strategy of a 4-drug regimen with the aforementioned drugs and statins. The cost-effectiveness ratio of 80% coverage with the polypill would be $1,690 ($1,220 to $2,410) per disability-adjusted life years averted. CONCLUSIONS: Policies expanding both treatment and preventive therapies are cost-effective, based on gross domestic product per capita comparison. Introducing the polypill would be more effective than providing its components separately, even without accounting for the likely increase in treatment adherence.