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Background: There is an urgent need for improved estimations of the burden of tuberculosis (TB)., Objective: To develop a new quantitative method based on mathematical modelling, and to demonstrate its application to TB in India., Design: We developed a simple model of TB transmission dynamics to estimate the annual incidence of TB disease from the annual risk of tuberculous infection and prevalence of smear-positive TB. We first compared model estimates for annual infections per smear-positive TB case using previous empirical estimates from China, Korea and the Philippines. We then applied the model to estimate TB incidence in India, stratified by urban and rural settings., Results: Study model estimates show agreement with previous empirical estimates. Applied to India, the model suggests an annual incidence of smear-positive TB of 89.8 per 100 000 population (95%CI 56.8-156.3). Results show differences in urban and rural TB: while an urban TB case infects more individuals per year, a rural TB case remains infectious for appreciably longer, suggesting the need for interventions tailored to these different settings., Conclusions: Simple models of TB transmission, in conjunction with necessary data, can offer approaches to burden estimation that complement those currently being used.

Background: Against the backdrop of renewed efforts to control tuberculosis (TB) worldwide, there is a need for improved methods to estimate the public health impact of TB programmes. Such methods should not only address the improved outcomes amongst those receiving care but should also account for the impact of TB services on reducing transmission., Methods: Vital registration data in India are not sufficiently reliable for estimates of TB mortality. As an alternative approach, we developed a mathematical model of TB transmission dynamics and mortality, capturing the scale-up of DOTS in India, through the rollout of the Revised National TB Control Programme (RNTCP). We used available data from the literature to calculate TB mortality hazards amongst untreated TB; amongst cases treated under RNTCP; and amongst cases treated under non-RNTCP conditions. Using a Bayesian evidence synthesis framework, we combined these data with current estimates for the TB burden in India to calibrate the transmission model. We simulated the national TB epidemic in the presence and absence of the DOTS programme, measuring lives saved as the difference in TB deaths between these scenarios., Results: From 1997 to 2016, India's RNTCP has saved 7.75 million lives (95% Bayesian credible interval 6.29-8.82 million). We estimate that 42% of this impact was due to the 'indirect' effects of the RNTCP in averting transmission as well as improving treatment outcomes., Conclusions: When expanding high-quality TB services, a substantial proportion of overall impact derives from preventive, as well as curative, benefits. Mathematical models, together with sufficient data, can be a helpful tool in estimating the true population impact of major disease control programmes.

More than 2 million visits for skin and soft tissue infections (SSTIs) are seen in US emergency departments (EDs) yearly. Up to 50% of patients with SSTIs, suffer from recurrences, but associated factors remain poorly understood. We performed a retrospective study of patients with primary diagnosis of SSTI between 2005 and 2011 using California ED discharge data from the State Emergency Department Databases and State Inpatient Databases. Using a multivariable logistic regression, we examined factors associated with a repeat SSTI ED visits up to 6 months after the initial SSTI. Among 197 371 SSTIs, 16·3% were associated with a recurrent ED visit. We found no trend in recurrent visits over time (χ 2 trend = 0·68, P = 0·4). Race/ethnicity, age, geographical location, household income, and comorbidities were all associated with recurrent visits. Recurrent ED visits were associated with drug/alcohol abuse or liver disease [odds ratio (OR) 1·4, 95% confidence interval (CI) 1·3-1·4], obesity (OR 1·3, 95% CI 1·2-1·4), and in infections that were drained (OR 1·1, 95% CI 1·1-1·1) and inversely associated with hospitalization after initial ED visit (OR 0·4, 95% CI 0·3-0·4). In conclusion, we found several patient-level factors associated with recurrent ED visits. Identification of these high-risk groups is critical for future ED-based interventions.

Background: Although 93% of 12- to 23-month-old children in India receive at least one vaccine, typically Bacillus Calmette-Guérin, only 75% complete the recommended three doses of diphtheria-pertussis-tetanus (DPT, also referred to as DTP) vaccine. Determinants can be different for nonvaccination and dropout but have not been examined in earlier studies. We use the three-dose DPT series as a proxy for the full sequence of recommended childhood vaccines and examine the determinants of DPT nonvaccination and dropout between doses 1 and 3., Methods: We analyzed data on 75,728 6- to 23-month-old children in villages across India to study demand- and supply-side factors determining nonvaccination with DPT and dropout between DPT doses 1 and 3, using a multilevel approach. Data come from the District Level Household and Facility Survey 3 (2007-08)., Results: Individual- and household-level factors were associated with both DPT nonvaccination and dropout between doses 1 and 3. Children whose mothers had no schooling were 2.3 times more likely not to receive any DPT vaccination and 1.5 times more likely to drop out between DPT doses 1 and 3, compared with children whose mothers had 10 or more years of schooling. Although supply-side factors related to availability of public health facilities and immunization-related health workers in villages were not correlated with dropout between DPT doses 1 and 3, children in districts where 46% or more villages had a healthcare subcentre were 1.5 times more likely to receive at least one dose of DPT vaccine compared with children in districts where 30% or fewer villages had subcentres., Conclusions: Nonvaccination with DPT in India is influenced by village- and district-level contextual factors over and above individuals' background characteristics. Dropout between DPT doses 1 and 3 is associated more strongly with demand-side factors than with village- and district-level supply-side factors., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The widespread use of antibiotics in humans and animals has contributed to growing rates of antibiotic resistance. Previously treatable bacterial infections now require the last line of antibiotics or are untreatable. The current antibiotic of last resort for carbapenem-resistant Gram-negative bacterial infections is often colistin. Evidence for the shifting pattern of colistin resistance and how the international community should respond are discussed in this review., Methods: The literature on colistin resistance was reviewed., Results: Plasmid-mediated colistin resistance encoded by mcr-1 was first documented in China during the routine surveillance of food animals. This has been followed by similar reports across a wide geographic area, in humans, animals, and the environment. The mcr-1 gene has been reported among human isolates in 29 countries, related to environmental samples in four countries, and in food animals and other animals in 28 countries. More recently, a second gene encoding resistance, mcr-2, has been isolated from porcine and bovine Escherichia coli., Conclusion: The emergence and horizontal transmission of colistin resistance highlights the need for heightened stewardship efforts across the One Health platform for this antibiotic of last resort, and indeed for all antibiotics used in animals and humans., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the association between the income status of a country and the prevalence of antimicrobial resistance (AMR) in the three most common bacteria causing infections in hospitals and in the community: third-generation cephalosporin (3GC)-resistant Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), and 3GC-resistant Klebsiella species., Methods: Using 2013-2014 country-specific data from the ResistanceMap repository and the World Bank, the association between the prevalence of AMR in invasive samples and the gross national income (GNI) per capita was investigated through linear regression with robust standard errors. To account for non-linear association with the dependent variable, GNI per capita was log-transformed., Results: The models predicted an 11.3% (95% confidence interval (CI) 6.5-16.2%), 18.2% (95% CI 11-25.5%), and 12.3% (95% CI 5.5-19.1%) decrease in the prevalence of 3GC-resistant E. coli, 3GC-resistant Klebsiella species, and MRSA, respectively, for each log GNI per capita. The association was stronger for 3GC-resistant E. coli and Klebsiella species than for MRSA., Conclusions: A significant negative association between GNI per capita and the prevalence of MRSA and 3GC-resistant E. coli and Klebsiella species was found. These results underscore the urgent need for new policies aimed at reducing AMR in resource-poor settings., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: High levels of maternal mortality and large associated inequalities exist in low-income and middle-income countries. Adolescent pregnancies remain common, and pregnant adolescent women face elevated risks of maternal mortality and poverty. We examined the distribution across socioeconomic groups of maternal deaths and impoverishment among adolescent girls (15-19 years old) in Niger, which has the highest total fertility rate globally, and India, which has the largest number of maternal deaths., Methods: In Niger and India, among adolescent girls, we estimated the distribution per income quintile of: the number of maternal deaths; and the impoverishment, measured by calculating the number of cases of catastrophic health expenditure incurred, caused by complicated pregnancies. We also examined the potential impact on maternal deaths and poverty of increasing adolescent girls' level of education by 1 year. We used epidemiological and cost inputs sourced from surveys and the literature., Results: The number of maternal deaths would be larger among the poorer adolescents than among the richer adolescents in Niger and India. Impoverishment would largely incur among the richer adolescents in Niger and among the poorer adolescents in India. Increasing educational attainment of adolescent girls might avert both a large number of maternal deaths and a significant number of cases of catastrophic health expenditure in the 2 countries., Conclusions: Adolescent pregnancies can lead to large equity gaps and substantial impoverishment in low-income and middle-income countries. Increasing female education can reduce such inequalities and provide financial risk protection and poverty alleviation to adolescent girls., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Competing Interests: Competing interests: None declared.

Objective: There have been no long-term studies on trends in antibiotic resistance (ABR) on a national scale in India. Using a private laboratory network, the ABR patterns of organisms most commonly associated with bacteremia, obtained from patients across India between 2008 and 2014, were examined., Methods: A retrospective study of patient blood cultures collected over a 7-year period (January 1, 2008-December 31, 2014) was conducted. Data on the microorganism(s) identified and their antimicrobial susceptibility were obtained from SRL Diagnostics (Mumbai, India)., Results: Of 135268 blood cultures, 18695 (14%) had at least one identified pathogen. In addition to continual high rates of methicillin-resistant Staphylococcus aureus (MRSA; approximately 44.2%), high resistance to nalidixic acid among Salmonella Typhi (98%) was observed, and carbapenem resistance increased in both Escherichia coli (7.8% to 11.5%; p=0.332) and Klebsiella pneumoniae (41.5% to 56.6%; p<0.001). Carbapenem resistance was also stable and high for both Acinetobacter species (approximately 69.6%) and Pseudomonas aeruginosa (approximately 49%). Resistance was also detected to colistin in the Gram-negatives and to vancomycin and linezolid in S. aureus., Conclusion: Increasing resistance to antibiotics of last-resort, particularly among Gram-negatives, suggests an urgent need for new antibiotics and improved antimicrobial stewardship programs in India., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aim: Coinfecting bacterial pathogens are a major cause of morbidity and mortality in influenza. However, there remains a paucity of literature on the magnitude of coinfection in influenza patients., Method: A systematic search of MeSH, Cochrane Library, Web of Science, SCOPUS, EMBASE, and PubMed was performed. Studies of humans in which all individuals had laboratory confirmed influenza, and all individuals were tested for an array of common bacterial species, met inclusion criteria., Results: Twenty-seven studies including 3215 participants met all inclusion criteria. Common etiologies were defined from a subset of eight articles. There was high heterogeneity in the results (I(2)  = 95%), with reported coinfection rates ranging from 2% to 65%. Although only a subset of papers were responsible for observed heterogeneity, subanalyses and meta-regression analysis found no study characteristic that was significantly associated with coinfection. The most common coinfecting species were Streptococcus pneumoniae and Staphylococcus aureus, which accounted for 35% (95% CI, 14%-56%) and 28% (95% CI, 16%-40%) of infections, respectively; a wide range of other pathogens caused the remaining infections. An assessment of bias suggested that lack of small-study publications may have biased the results., Conclusions: The frequency of coinfection in the published studies included in this review suggests that although providers should consider possible bacterial coinfection in all patients hospitalized with influenza, they should not assume all patients are coinfected and be sure to properly treat underlying viral processes. Further, high heterogeneity suggests additional large-scale studies are needed to better understand the etiology of influenza bacterial coinfection., (© 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objective: In March 2014, India, the country with historically the highest burden of polio, was declared polio free, with no reported cases since January 2011. We estimate the health and economic benefits of polio elimination in India with the oral polio vaccine (OPV) during 1982-2012., Methods: Based on a pre-vaccine incidence rate, we estimate the counterfactual burden of polio in the hypothetical absence of the national polio elimination program in India. We attribute differences in outcomes between the actual (adjusted for under-reporting) and hypothetical counterfactual scenarios in our model to the national polio program. We measure health benefits as averted polio incidence, deaths, and disability adjusted life years (DALYs). We consider two methods to measure economic benefits: the value of statistical life approach, and equating one DALY to the Gross National Income (GNI) per capita., Results: We estimate that the National Program against Polio averted 3.94 million (95% confidence interval [CI]: 3.89-3.99 million) paralytic polio cases, 393,918 polio deaths (95% CI: 388,897- 398,939), and 1.48 billion DALYs (95% CI: 1.46-1.50 billion). We also estimate that the program contributed to a $1.71 trillion (INR 76.91 trillion) gain (95% CI: $1.69-$1.73 trillion [INR 75.93-77.89 trillion]) in economic productivity between 1982 and 2012 in our base case analysis. Using the GNI and DALY method, the economic gain from the program is estimated to be $1.11 trillion (INR 50.13 trillion) (95% CI: $1.10-$1.13 trillion [INR 49.50-50.76 trillion]) over the same period., Conclusion: India accrued large health and economic benefits from investing in polio elimination efforts. Other programs to control/eliminate more vaccine-preventable diseases are likely to contribute to large health and economic benefits in India.

Background: Schizophrenia remains a priority condition in mental health policy and service development because of its early onset, severity and consequences for affected individuals and households., Aims and Methods: This paper reports on an 'extended' cost-effectiveness analysis (ECEA) for schizophrenia treatment in India, which seeks to evaluate through a modeling approach not only the costs and health effects of intervention but also the consequences of a policy of universal public finance (UPF) on health and financial outcomes across income quintiles., Results: Using plausible values for input parameters, we conclude that health gains from UPF are concentrated among the poorest, whereas the non-health gains in the form of out-of-pocket private expenditures averted due to UPF are concentrated among the richest income quintiles. Value of insurance is the highest for the poorest quintile and declines with income., Conclusions: Universal public finance can play a crucial role in ameliorating the adverse economic and social consequences of schizophrenia and its treatment in resource-constrained settings where health insurance coverage is generally poor. This paper shows the potential distributional and financial risk protection effects of treating schizophrenia.

Approximately 900 000 newborn children die every year in India, accounting for 28% of neonatal deaths globally. In 2011, India introduced a home-based newborn care (HBNC) package to be delivered by community health workers across rural areas. We estimate the disease and economic burden that could be averted by scaling up the HBNC in rural India using IndiaSim, an agent-based simulation model, to examine two interventions. In the first intervention, the existing community health worker network begins providing HBNC for rural households without access to home- or facility-based newborn care, as introduced by India's recent programme. In the second intervention, we consider increased coverage of HBNC across India so that total coverage of neonatal care (HBNC or otherwise) in the rural areas of each state reaches at least 90%. We find that compared with a baseline of no coverage, providing the care package through the existing network of community health workers could avert 48 [95% uncertainty range (UR) 34-63] incident cases of severe neonatal morbidity and 5 (95% UR 4-7) related deaths, save $4411 (95% UR $3088-$5735) in out-of-pocket treatment costs, and provide $285 (95% UR $200-$371) in value of insurance per 1000 live births in rural India. Increasing the coverage of HBNC to 90% will avert an additional 9 (95% UR 7-12) incident cases, 1 death (95% UR 0.72-1.33), and $613 (95% UR $430-$797) in out-of-pocket expenditures, and provide $55 (95% UR $39-$72) in incremental value of insurance per 1000 live births. Intervention benefits are greater for lower socioeconomic groups and in the poorer states of Chhattisgarh, Uttarakhand, Bihar, Assam and Uttar Pradesh., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background & Objectives: India's Universal Immunization Programme (UIP) is one of the largest programmes in the world in terms of quantities of vaccines administered, number of beneficiaries, number of immunization sessions, and geographical extent and diversity of areas covered. Strategic planning for the Programme requires credible information on the cost of achieving the objectives and the financial resources needed at national, State, and district levels. We present here expenditures on immunization services in India in 2012 (baseline) and projected costs for five years (2013-2017)., Methods: Data were collected from the Immunization Division of the Ministry of Health and Family Welfare, Government of India, and immunization partners, such as the World Health Organization and UNICEF. The cost components were immunization personnel, vaccines and injection supplies, transportation, trainings, social mobilization, advocacy and communication activities, disease surveillance, Programme management, maintenance of cold chain and other equipment, and capital costs., Results: Total baseline expenditure was ₹ 3,446 crore [1 crore = 10 million] (US$718 million), including shared personnel costs. In 2012, the government paid for 90 per cent of the Programme. Total resource requirements for 2013-2017 are ₹ 34,336 crore (US$ 5, 282 million). Allocations for vaccines increase from ₹ 511 crore in 2013 to ₹ 3,587 crore in 2017 as new vaccines are assumed to be introduced in the Programme., Interpretation & Conclusions: The projections show that the government immunization budget will be double in 2017 as compared to 2013. It will increase from ₹ 4,570 crore in 2013 to ₹ 9,451 crore in 2017., Competing Interests: None.

Investments in cancer control--prevention, detection, diagnosis, surgery, other treatment, and palliative care--are increasingly needed in low-income and particularly in middle-income countries, where most of the world's cancer deaths occur without treatment or palliation. To help countries expand locally appropriate services, Cancer (the third volume of nine in Disease Control Priorities, 3rd edition) developed an essential package of potentially cost-effective measures for countries to consider and adapt. Interventions included in the package are: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioids. These interventions would cost an additional US$20 billion per year worldwide, constituting 3% of total public spending on health in low-income and middle-income countries. With implementation of an appropriately tailored package, most countries could substantially reduce suffering and premature death from cancer before 2030, with even greater improvements in later decades., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.

The burden of mental, neurological, and substance use (MNS) disorders increased by 41% between 1990 and 2010 and now accounts for one in every 10 lost years of health globally. This sobering statistic does not take into account the substantial excess mortality associated with these disorders or the social and economic consequences of MNS disorders on affected persons, their caregivers, and society. A wide variety of effective interventions, including drugs, psychological treatments, and social interventions, can prevent and treat MNS disorders. At the population-level platform of service delivery, best practices include legislative measures to restrict access to means of self-harm or suicide and to reduce the availability of and demand for alcohol. At the community-level platform, best practices include life-skills training in schools to build social and emotional competencies. At the health-care-level platform, we identify three delivery channels. Two of these delivery channels are especially relevant from a public health perspective: self-management (eg, web-based psychological therapy for depression and anxiety disorders) and primary care and community outreach (eg, non-specialist health worker delivering psychological and pharmacological management of selected disorders). The third delivery channel, hospital care, which includes specialist services for MNS disorders and first-level hospitals providing other types of services (such as general medicine, HIV, or paediatric care), play an important part for a smaller proportion of cases with severe, refractory, or emergency presentations and for the integration of mental health care in other health-care channels, respectively. The costs of providing a significantly scaled up package of specified cost-effective interventions for prioritised MNS disorders in low-income and lower-middle-income countries is estimated at US$3-4 per head of population per year. Since a substantial proportion of MNS disorders run a chronic and disabling course and adversely affect household welfare, intervention costs should largely be met by government through increased resource allocation and financial protection measures (rather than leaving households to pay out-of-pocket). Moreover, a policy of moving towards universal public finance can also be expected to lead to a far more equitable allocation of public health resources across income groups. Despite this evidence, less than 1% of development assistance for health and government spending on health in low-income and middle-income countries is allocated to the care of people with these disorders. Achieving the health gains associated with prioritised interventions will require not just financial resources, but committed and sustained efforts to address a range of other barriers (such as paucity of human resources, weak governance, and stigma). Ultimately, the goal is to massively increase opportunities for people with MNS disorders to access services without the prospect of discrimination or impoverishment and with the hope of attaining optimal health and social outcomes., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Ramanan Laxminarayan and Ranjit Roy Chaudhury examine the factors encouraging the emergence of antibiotic resistance in India, the implications nationally and internationally, and what might be done to help.

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., (© 2016 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.)

Securing access to effective antimicrobials is one of the greatest challenges today. Until now, efforts to address this issue have been isolated and uncoordinated, with little focus on sustainable and international solutions. Global collective action is necessary to improve access to life-saving antimicrobials, conserving them, and ensuring continued innovation. Access, conservation, and innovation are beneficial when achieved independently, but much more effective and sustainable if implemented in concert within and across countries. WHO alone will not be able to drive these actions. It will require a multisector response (including the health, agriculture, and veterinary sectors), global coordination, and financing mechanisms with sufficient mandates, authority, resources, and power. Fortunately, securing access to effective antimicrobials has finally gained a place on the global political agenda, and we call on policy makers to develop, endorse, and finance new global institutional arrangements that can ensure robust implementation and bold collective action., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In a highly interconnected world, immunizing infections are a transboundary problem, and their control and elimination require international cooperation and coordination. In the absence of a global or regional body that can impose a universal vaccination strategy, each individual country sets its own strategy. Mobility of populations across borders can promote free-riding, because a country can benefit from the vaccination efforts of its neighbours, which can result in vaccination coverage lower than the global optimum. Here we explore whether voluntary coalitions that reward countries that join by cooperatively increasing vaccination coverage can solve this problem. We use dynamic epidemiological models embedded in a game-theoretic framework in order to identify conditions in which coalitions are self-enforcing and therefore stable, and thus successful at promoting a cooperative vaccination strategy. We find that countries can achieve significantly greater vaccination coverage at a lower cost by forming coalitions than when acting independently, provided a coalition has the tools to deter free-riding. Furthermore, when economically or epidemiologically asymmetric countries form coalitions, realized coverage is regionally more consistent than in the absence of coalitions., (© 2016 The Authors.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Heatwaves are one of the most deadly weather-related events in the United States and account for more deaths annually than hurricanes, tornadoes, floods, and earthquakes combined. However, there are few statistically rigorous studies of the effect of heatwaves on emergency department (ED) arrivals. A better understanding of this relationship can help hospitals plan better and provide better care for patients during these types of events., Methods:  A retrospective review of all ED patient arrivals that occurred from April 15 through August 15 for the years 2008 through 2013 was performed. Daily patient arrival data were combined with weather data (temperature and humidity) to examine the potential relationships between the heat index and ED arrivals as well as the length of time patients spend in the ED using generalized additive models. In particular the effect the 2012 heat wave that swept across the United States, and which was hypothesized to increase arrivals was examined., Results:  While there was no relationship found between the heat index and arrivals on a single day, a non-linear relationship was found between the mean three-day heat index and the number of daily arrivals. As the mean three-day heat index initially increased, the number of arrivals significantly declined. However, as the heat index continued to increase, the number of arrivals increased. It was estimated that there was approximately a 2% increase in arrivals when the mean heat index for three days approached 100°F. This relationship was strongest for adults aged 18-64, as well as for patients arriving with lower acuity. Additionally, a positive relationship was noted between the mean three-day heat index and the length of stay (LOS) for patients in the ED, but no relationship was found for the time from which a patient was first seen to when a disposition decision was made. No significant relationship was found for the effect of the 2012 heat wave on ED arrivals, though it did have an effect on patient LOS., Conclusion:  A single hot day has only a limited effect on ED arrivals, but continued hot weather has a cumulative effect. When the heat index is high (~90°F) for a number of days in a row, this curtails peoples activities, but if the heat index is very hot (~100°F) this likely results in an exacerbation of underlying conditions as well as heat-related events that drives an increase in ED arrivals. Periods of high heat also affects the length of stay of patients either by complicating care or by making it more difficult to discharge patients.

A basic quantitative understanding of malaria transmission requires measuring the probability a mosquito becomes infected after feeding on a human. Parasite prevalence in mosquitoes is highly age-dependent, and the unknown age-structure of fluctuating mosquito populations impedes estimation. Here, we simulate mosquito infection dynamics, where mosquito recruitment is modelled seasonally with fractional Brownian noise, and we develop methods for estimating mosquito infection rates. We find that noise introduces bias, but the magnitude of the bias depends on the 'colour' of the noise. Some of these problems can be overcome by increasing the sampling frequency, but estimates of transmission rates (and estimated reductions in transmission) are most accurate and precise if they combine parity, oocyst rates and sporozoite rates. These studies provide a basis for evaluating the adequacy of various entomological sampling procedures for measuring malaria parasite transmission from humans to mosquitoes and for evaluating the direct transmission-blocking effects of a vaccine., (© 2015 The Authors.)

In this review the existing evidence on the impact of Rashtriya Swasthya Bima Yojana (RSBY) is discussed in the context of international literature available on health insurance. We describe potential pathways through which health insurance can affect health and economic outcomes, discuss evidence from other developing countries, and identify potential biases and inconsistencies in existing studies on RSBY impact. Given the relatively recent introduction of RSBY, lack of quality, verifiable data on utilization patterns, and the absence of reliable evaluation studies, there is a need to exercise caution while assessing the merits of the programme. Considering the enormous potential and cost of the programme, we emphasize the need for a rigorous impact evaluation of RSBY. It will not only help capture the real impact of the scheme, but may also be able to estimate the extent of systemic inefficiencies at the level of the consumer.

Background: Although Plasmodium falciparum transmission frequently exhibits seasonal patterns, the drivers of malaria seasonality are often unclear. Given the massive variation in the landscape upon which transmission acts, intra-annual fluctuations are likely influenced by different factors in different settings. Further, the presence of potentially substantial inter-annual variation can mask seasonal patterns; it may be that a location has "strongly seasonal" transmission and yet no single season ever matches the mean, or synoptic, curve. Accurate accounting of seasonality can inform efficient malaria control and treatment strategies. In spite of the demonstrable importance of accurately capturing the seasonality of malaria, data required to describe these patterns is not universally accessible and as such localized and regional efforts at quantifying malaria seasonality are disjointed and not easily generalized., Methods: The purpose of this review was to audit the literature on seasonality of P. falciparum and quantitatively summarize the collective findings. Six search terms were selected to systematically compile a list of papers relevant to the seasonality of P. falciparum transmission, and a questionnaire was developed to catalogue the manuscripts., Results and Discussion: 152 manuscripts were identified as relating to the seasonality of malaria transmission, deaths due to malaria or the population dynamics of mosquito vectors of malaria. Among these, there were 126 statistical analyses and 31 mechanistic analyses (some manuscripts did both)., Discussion: Identified relationships between temporal patterns in malaria and climatological drivers of malaria varied greatly across the globe, with different drivers appearing important in different locations. Although commonly studied drivers of malaria such as temperature and rainfall were often found to significantly influence transmission, the lags between a weather event and a resulting change in malaria transmission also varied greatly by location., Conclusions: The contradicting results of studies using similar data and modelling approaches from similar locations as well as the confounding nature of climatological covariates underlines the importance of a multi-faceted modelling approach that attempts to capture seasonal patterns at both small and large spatial scales.

Antibiotic resistance, similar to climate change, is a shared global problem, but unlike climate change, national and local action produces direct localized benefits in addition to improving the global situation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Face-to-face social contacts are potentially important transmission routes for acute respiratory infections, and understanding the contact network can improve our ability to predict, contain, and control epidemics. Although workplaces are important settings for infectious disease transmission, few studies have collected workplace contact data and estimated workplace contact networks. We use contact diaries, architectural distance measures, and institutional structures to estimate social contact networks within a Swiss research institute. Some contact reports were inconsistent, indicating reporting errors. We adjust for this with a latent variable model, jointly estimating the true (unobserved) network of contacts and duration-specific reporting probabilities. We find that contact probability decreases with distance, and that research group membership, role, and shared projects are strongly predictive of contact patterns. Estimated reporting probabilities were low only for 0-5 min contacts. Adjusting for reporting error changed the estimate of the duration distribution, but did not change the estimates of covariate effects and had little effect on epidemic predictions. Our epidemic simulation study indicates that inclusion of network structure based on architectural and organizational structure data can improve the accuracy of epidemic forecasting models.

Background: Bidis, the most common smoking tobacco product in India, remain largely untaxed and are subject to very few regulations to discourage their use. A major argument against tax increases is the large potential loss of economic activity and employment in the bidi industry from reduced consumption., Methods: We used a nationally representative survey of unorganised bidi manufacturing firms (n=2841) in India to estimate the economic contribution of the industry., Results: We find that of the 35 states and union territories of India, the bidi industry operated across 17 states, with over 95% of its production concentrated in 10 states. Bidi manufacturing firms contributed 0.50% of total sales and 0.6% of the gross value added by the manufacturing economy in 2005-2006. The industry employed approximately 3.4 million full-time workers, which comprise about 0.7% of employment in all sectors. A further 0.7 million were part-time workers. Bidi workers were also among the lowest paid employees in India. The industry offered only 0.09% of all compensation provided in the manufacturing sector (organised and unorganised)., Conclusions: Considering the relatively small economic footprint of the bidi industry in India, higher excise taxes and regulations on bidis are unlikely to disrupt economic growth at an aggregate level, or lead to mass unemployment and economic hardship among small bidi workers. On average, the economic annual output per bidi worker is about US$143, which is an order of magnitude smaller than the large economic losses from the several hundred thousand deaths due to bidi smoking per year., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The Affordable Medicines Facility for malaria (AMFm) was conceived as a global market-based mechanism to increase access to effective malaria treatment and prolong effectiveness of artemisinin. Although results from a pilot implementation suggested that the subsidy was effective in increasing access to high-quality artemisinin combination therapies (ACTs), the Global Fund has converted AMFm into a country-driven mechanism whereby individual countries could choose to fund the subsidy from within their country envelopes. Because the initial costs of the subsidy in the pilot countries was higher than expected, countries are also exploring alternatives to a universal subsidy, such as subsidizing only child doses. We examined the incremental cost-effectiveness of a child-targeted policy using an age-structured bioeconomic model of malaria from the provider perspective. Because the vast majority of malaria deaths occur in children, targeting children could potentially improve the cost-effectiveness of the subsidy, though it would avert significantly fewer deaths. However, the benefits of a child-targeted subsidy (i.e. deaths averted) are eroded as leakage (i.e. older individuals taking young child-targeted doses) increases, with few of the benefits of a universal subsidy gained (i.e. reductions in overall prevalence). Although potentially more cost-effective, a child-targeted subsidy must contain measures to reduce the possibility of leakage.

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Demand for animal protein for human consumption is rising globally at an unprecedented rate. Modern animal production practices are associated with regular use of antimicrobials, potentially increasing selection pressure on bacteria to become resistant. Despite the significant potential consequences for antimicrobial resistance, there has been no quantitative measurement of global antimicrobial consumption by livestock. We address this gap by using Bayesian statistical models combining maps of livestock densities, economic projections of demand for meat products, and current estimates of antimicrobial consumption in high-income countries to map antimicrobial use in food animals for 2010 and 2030. We estimate that the global average annual consumption of antimicrobials per kilogram of animal produced was 45 mg⋅kg(-1), 148 mg⋅kg(-1), and 172 mg⋅kg(-1) for cattle, chicken, and pigs, respectively. Starting from this baseline, we estimate that between 2010 and 2030, the global consumption of antimicrobials will increase by 67%, from 63,151 ± 1,560 tons to 105,596 ± 3,605 tons. Up to a third of the increase in consumption in livestock between 2010 and 2030 is imputable to shifting production practices in middle-income countries where extensive farming systems will be replaced by large-scale intensive farming operations that routinely use antimicrobials in subtherapeutic doses. For Brazil, Russia, India, China, and South Africa, the increase in antimicrobial consumption will be 99%, up to seven times the projected population growth in this group of countries. Better understanding of the consequences of the uninhibited growth in veterinary antimicrobial consumption is needed to assess its potential effects on animal and human health.

Objectives: Despite a strong link between antibiotic use and resistance, and highly variable antibiotic consumption rates across the USA, drivers of differences in consumption rates are not fully understood. The objective of this study was to examine how provider density affects antibiotic prescribing rates across socioeconomic groups in the USA., Methods: We aggregated data on all outpatient antibiotic prescriptions filled in retail pharmacies in the USA in 2000 and 2010 from IMS Health into 3436 geographically distinct hospital service areas and combined this with socioeconomic and structural factors that affect antibiotic prescribing from the US Census. We then used fixed-effect models to estimate the interaction between poverty and the number of physician offices per capita (i.e. physician density) and the presence of urgent care and retail clinics on antibiotic prescribing rates., Results: We found large geographical variation in prescribing, driven in part by the number of physician offices per capita. For an increase of one standard deviation in the number of physician offices per capita there was a 25.9% increase in prescriptions per capita. However, the determinants of the prescription rate were dependent on socioeconomic conditions. In poorer areas, clinics substitute for traditional physician offices, reducing the impact of physician density. In wealthier areas, clinics increase the effect of physician density on the prescribing rate., Conclusions: In areas with higher poverty rates, access to providers drives the prescribing rate. However, in wealthier areas, where access is less of a problem, a higher density of providers and clinics increases the prescribing rate, potentially due to competition., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

In the last decade we have witnessed a dramatic increase in the proportion and absolute number of bacterial pathogens resistant to multiple antibacterial agents. Multidrug-resistant bacteria are currently considered as an emergent global disease and a major public health problem. The B-Debate meeting brought together renowned experts representing the main stakeholders (i.e. policy makers, public health authorities, regulatory agencies, pharmaceutical companies and the scientific community at large) to review the global threat of antibiotic resistance and come up with a coordinated set of strategies to fight antimicrobial resistance in a multifaceted approach. We summarize the views of the B-Debate participants regarding the current situation of antimicrobial resistance in animals and the food chain, within the community and the healthcare setting as well as the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global threat of antimicrobial resistance.

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., (© 2016 American Society for Nutrition.)

Information on population health indicators in India come from a number of surveys that vary in periodicity, scope and detail. In the case of immunization, the most recent coverage indicators are derived from the first round of Annual Health Survey (AHS-1, 2010-11), but these were conducted only in 9 of 35 states and union territories. The most recent national surveys of immunization coverage were conducted in 2009 (Coverage Evaluation Survey) by UNICEF. Therefore, reliable immunization coverage data for the entire country since 2009 is lacking. We used an established approach of small area estimation to predict coverage rates of several vaccinations for the remaining 26 states (not covered by AHS-1) in 2011. In our method, we considered a linear mixed model that combines data from five cross sectional surveys representing five different time points. Our model encompasses sampling error of the survey estimates, area specific random effects, autocorrelated area by time random effects and hence, borrows strength across areas and time points both. Model-based estimates for 2011 are almost identical to the AHS-1 estimates for the nine states, suggesting that our model provides reliable prediction of vaccination coverage as AHS-1 estimates are highly precise because of their large sample size. Results indicate that coverage inequality between rural and urban areas has been reduced significantly for most states in India. The National Rural Health Mission has had both supply side and demand side effects on the immunization programme in rural India. In combination, these effects may have contributed to the reduction of vaccination coverage gaps between urban and rural areas., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Legal prohibitions on sex-selective abortions are proliferating in the United States. Eight state legislatures have banned abortions sought on the basis of the sex of the fetus, 21 states have considered such laws since 2009, and a similar bill is pending in U.S. Congress. These laws have been introduced and enacted without any empirical data about their impact or effectiveness. Prior studies of U.S. Census data found sex ratios among foreign-born Chinese, Korean and Indian immigrants were skewed in favor of boys, but only in families where there were already one or two girls. Using the variation in the timing of bans in Illinois and Pennsylvania as natural experiments, we compare the pre-ban and post-ban sex ratios of certain Asian newborn children in these states over 12-year periods. We then compare these ratios with the sex ratios of Asian newborn children in neighboring states during the same period. We find that the bans in Illinois and Pennsylvania are not associated with any changes in sex ratios at birth among Asians. In Illinois and its neighboring states, the sex ratio at birth of Asian children was not male-biased during our study period. On the other hand, the sex ratio at birth among Asians in Pennsylvania and its neighboring states was skewed slightly in favor of boys, but the enactment of the ban did not normalize the sex ratio. This strongly suggests that sex-selective abortion bans have had no impact on the practice of sex selection, to the extent that it occurs, in these states. This finding is highly relevant to legislative and policy debates in the U.S. Congress and state legislatures where sex-selective abortion laws are being considered.

Background: Enterobacteriaceae infections resistant to extended-spectrum β-lactams are an emerging problem in children. We used a large database of clinical isolates to describe the national epidemiology of extended-spectrum β-lactamase (ESBL)-producing and third-generation cephalosporin-resistant (G3CR) Enterobacteriaceae., Methods: Antimicrobial susceptibilities of Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis reported to ∼300 laboratories participating in The Surveillance Network (TSN) between January 1999 and December 2011 were used to phenotypically identify G3CR and ESBL isolates cultured from patients <18 years. Bi-annual trends in the prevalence of each phenotype were stratified by species, patient location, culture site, age, and region. Children of age 0-1 years were excluded from analysis as data were only available from 2010 onwards., Results: Out of 368,398 pediatric isolates, 1.97% (7255) were identified as G3CR, and 0.47% (1734) as ESBL producers. The prevalence of both phenotypes increased, respectively, from 1.39% and 0.28% in 1999-2001 to 3% and 0.92% in 2010-2011. Trends were significant across all demographic and age groups, including outpatients, with the highest proportion of isolates in the 1-5-year-old age group. The majority of G3CR and ESBL isolates were E. coli (67.8% and 65.2%, respectively). Among ESBLs, resistance to ≥3 antibiotic classes was 74%. The lower regional prevalence of ESBL-producing bacteria in the upper Midwest relative to the rest of the country is consistent with recent local data., Conclusions: Rates of G3CR and ESBL infections in children are increasing in both inpatient and ambulatory settings nationally. The identification of host factors and exposures leading to infection in children is essential., (© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae infections are an emerging problem in children. We sought to identify risk factors and describe outcomes associated with pediatric ESBL-producing bacterial infections at 2 hospitals in Chicago, IL from 2008 to 2011., Methods: A case-case-control study of children aged 0-17 years was conducted. Cases of Escherichia coli, Klebsiella, and Proteus spp. ESBL-producing bacterial infections (n = 30) were compared to uninfected controls and in parallel, cases of non-ESBL-producing bacterial infections (n = 30) were compared to uninfected controls (n = 60). We then qualitatively compared these results., Results: Median age of cases was 1.06 years; 62% of isolates were from urine, and 60% were E. coli. By multivariable analysis, ESBL cases were 5.7 and 3.3 times more likely to have gastrointestinal (P = .001; 95% confidence interval [CI] 1.9-17.0) and neurologic (P = .001; 95% CI 1.1-3.7) comorbidities, respectively, than controls; non-ESBL cases were also more likely to have gastrointestinal comorbidities than controls (P = .014; odds ratio 3.6; 95% CI 1.2-10.1). Study period prevalence remained stable (1.7%). Most (60%) infections occurred in the intensive care unit; however, 30% of children presented in the outpatient setting. Seventy-seven percent of isolates were multidrug resistant (ie, resistant to ≥3 antibiotic classes). Recurrence of infection occurred in 17% of ESBL cases. Crude mortality rates (7%) did not differ between cases and controls., Conclusions: The incidence of pediatric infection due to ESBL-positive Enterobacteriaceae was stable at 2 large tertiary-care medical centers over a 4-year period. Multidrug resistance in pediatric ESBL isolates is common. Risk factors for infection due to ESBL-producing bacteria include neurologic medical conditions., (© The Author 2014. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Modification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy., Methods: We did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable., Findings: Across the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive culture (1·99, 1·20-3·29)., Interpretation: Broad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials., Funding: US Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security., (Copyright © 2014 Elsevier Ltd. All rights reserved.)