Association between antimicrobial stewardship programs and antibiotic use globally: a systematic review and meta-analysis

IMPORTANCE: Antimicrobial resistance continues to spread rapidly at a global scale. Little evidence exists on the association of antimicrobial stewardship programs (ASPs) with the consumption of antibiotics across health care and income settings. OBJECTIVE: To synthesize current evidence regarding the association between antimicrobial stewardship programs and the consumption of antibiotics globally. DATA SOURCES: PubMed, Web of Science, and Scopus databases were searched from August 1, 2010, to Aug 1, 2020. Additional studies from the bibliography sections of previous systematic reviews were included. STUDY SELECTION: Original studies of the association of ASPs with antimicrobial consumption across health care and income settings. Animal and environmental studies were excluded. DATA EXTRACTION AND SYNTHESIS: Following the Preferred Reporting Items in Systematic Reviews and Meta-Analyses guideline, the pooled association of targeted ASPs with antimicrobial consumption was measured using multilevel random-effects models. The Effective Public Health Practice Project quality assessment tool was used to assess study quality. MAIN OUTCOMES AND MEASURES: The main outcome measures were proportion of patients receiving an antibiotic prescription and defined daily doses per 100 patient-days. RESULTS: Overall, 52 studies (with 1 794 889 participants) measured the association between ASPs and antimicrobial consumption and were included, with 40 studies conducted in high-income countries and 12 in low- and middle-income countries (LMICs). ASPs were associated with a 10% (95% CI, 4%-15%) reduction in antibiotic prescriptions and a 28% reduction in antibiotic consumption (rate ratio, 0.72; 95% CI, 0.56-0.92). ASPs were also associated with a 21% (95% CI, 5%-36%) reduction in antibiotic consumption in pediatric hospitals and a 28% reduction in World Health Organization watch groups antibiotics (rate ratio, 0.72; 95% CI, 0.56-0.92). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, ASPs appeared to be effective in reducing antibiotic consumption in both hospital and nonhospital settings. Impact assessment of ASPs in resource-limited settings remains scarce; further research is needed on how to best achieve reductions in antibiotic use in LMICs

Impact of scaling up prenatal nutrition interventions on human capital outcomes in low- and middle-income countries: a modeling analysis

BACKGROUND: Prenatal nutrition interventions can lead to improved birth outcomes, which in turn are associated with better education and human capital outcomes later in life. OBJECTIVE: We estimated the impact of scaling up iron-folic acid (IFA), calcium, multiple micronutrient (MMS), and balanced energy protein (BEP) supplementation for pregnant women, on human capital outcomes in low- and middle-income countries (LMIC). METHODS: We used mathematical modeling with proportional reductions in adverse birth outcomes to estimate the potential gains in school years and lifetime income due to scaling up each prenatal nutrition intervention. Estimates of intervention effects on birth outcomes were derived from meta-analyses of randomized trials. Estimates of the associations between birth outcomes and schooling and lifetime income were derived from de novo meta-analyses of observational studies. RESULTS: Across 132 LMIC, scaling up prenatal nutrition interventions to 90% coverage was estimated to increase school years and lifetime income per birth cohort by: 2.28 million y (95% uncertainty intervals (UI): -0.44, 6.26) and $8.26 billion (95$18.9 billion (95% UI: 0.59, 44.6) for calcium; 5.02 million y (95% UI: 1.07, 11.0) and $18.1 billion (95$1.34 billion (95% UI: -1.10, 3.10 billion) for BEP supplementation. South Asia and Sub-Saharan Africa tended to have the largest estimated regional gains in school years for scaling up each intervention due to the large population size and high burden of poor birth outcomes. Absolute income benefits for each intervention were estimated to be the largest in Latin America, where returns to education and incomes are higher relative to other regions. CONCLUSION: Increasing coverage of prenatal nutrition interventions in LMIC may lead to substantial gains in schooling and lifetime income. Decision makers should consider the potential long-term human capital returns of investments in maternal nutrition

Large gains in schooling and income are possible from minimizing adverse birth outcomes in 121 low- and middle-income countries: a modelling study

While the global contributions of adverse birth outcomes to child morbidity and mortality is relatively well documented, the potential long-term schooling and economic consequences of adverse birth outcomes has not been estimated. We sought to quantify the potential schooling and lifetime income gains associated with reducing the excess prevalence of adverse birth outcomes in 121 low- and middle-income countries. We used a linear deterministic model to estimate the potential gains in schooling and lifetime income that may be achieved by attaining theoretical minimum prevalence of low birthweight, preterm birth and small-for-gestational age births at the national, regional, and global levels. We estimated that potential total gains across the 121 countries from reducing low birthweight to the theoretical minimum were 20.3 million school years (95% CI: 6.0,34.8) and US$68.8 billion (95$ 41.9 billion (95% CI: 6.1,80.9) in lifetime income. The potential gains from small-for-gestational age were 39.5 million (95% CI: 19.1,60.3) school years and US$113.6 billion (95% CI: 55.5,174.2) in lifetime income gained. In summary, reducing the excess prevalence of low birthweight, preterm birth or small-for-gestational age births in low- and middle-income countries may lead to substantial long-term human capital gains in addition to benefits on child mortality, growth, and development as well as on risk of non-communicable diseases in adults and other consequences across the life course

Birth weight and adult earnings: a systematic review and meta-analysis

While substantial evidence has identified low birth weight (LBW; <2500 g) as a risk factor for early life morbidity, mortality and poor childhood development, relatively little is known on the links between birth weight and economic outcomes in adulthood. The objective of this study was to systematically review the economics (EconLit) and biomedical literature (Medline) and estimate the pooled association between birth weight and adult earnings. A total of 15 studies from mostly high-income countries were included. On average, each standard deviation increase in birth weight was associated with a 2.75% increase in annual earnings [(95% CI: 1.44 to 4.07); 9 estimates]. A negative, but not statistically significant, association was found between being born LBW and earnings, compared to individuals not born LBW [mean difference: -3.41% (95% CI: -7.55 to 0.73); 7 estimates]. No studies from low-income countries were identified and all studies were observational. Overall, birth weight was consistently associated with adult earnings, and therefore, interventions that improve birth weight may provide beneficial effects on adult economic outcomes

Association Between Antimicrobial Stewardship Programs and Antibiotic Use Globally: A Systematic Review and Meta-Analysis.

IMPORTANCE: Antimicrobial resistance continues to spread rapidly at a global scale. Little evidence exists on the association of antimicrobial stewardship programs (ASPs) with the consumption of antibiotics across health care and income settings. OBJECTIVE: To synthesize current evidence regarding the association between antimicrobial stewardship programs and the consumption of antibiotics globally. DATA SOURCES: PubMed, Web of Science, and Scopus databases were searched from August 1, 2010, to Aug 1, 2020. Additional studies from the bibliography sections of previous systematic reviews were included. STUDY SELECTION: Original studies of the association of ASPs with antimicrobial consumption across health care and income settings. Animal and environmental studies were excluded. DATA EXTRACTION AND SYNTHESIS: Following the Preferred Reporting Items in Systematic Reviews and Meta-Analyses guideline, the pooled association of targeted ASPs with antimicrobial consumption was measured using multilevel random-effects models. The Effective Public Health Practice Project quality assessment tool was used to assess study quality. MAIN OUTCOMES AND MEASURES: The main outcome measures were proportion of patients receiving an antibiotic prescription and defined daily doses per 100 patient-days. RESULTS: Overall, 52 studies (with 1 794 889 participants) measured the association between ASPs and antimicrobial consumption and were included, with 40 studies conducted in high-income countries and 12 in low- and middle-income countries (LMICs). ASPs were associated with a 10% (95% CI, 4%-15%) reduction in antibiotic prescriptions and a 28% reduction in antibiotic consumption (rate ratio, 0.72; 95% CI, 0.56-0.92). ASPs were also associated with a 21% (95% CI, 5%-36%) reduction in antibiotic consumption in pediatric hospitals and a 28% reduction in World Health Organization watch groups antibiotics (rate ratio, 0.72; 95% CI, 0.56-0.92). CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, ASPs appeared to be effective in reducing antibiotic consumption in both hospital and nonhospital settings. Impact assessment of ASPs in resource-limited settings remains scarce; further research is needed on how to best achieve reductions in antibiotic use in LMICs

Getting It Straight: Accommodating Rectilinear Behavior in Captive Snakes-A Review of Recommendations and Their Evidence Base.

Snakes are sentient animals and should be subject to the accepted general welfare principles of other species. However, they are also the only vertebrates commonly housed in conditions that prevent them from adopting rectilinear behavior (ability to fully stretch out). To assess the evidence bases for historical and current guidance on snake spatial considerations, we conducted a literature search and review regarding recommendations consistent with or specifying ≥1 × and <1 × snake length enclosure size. We identified 65 publications referring to snake enclosure sizes, which were separated into three categories: peer-reviewed literature (article or chapter appearing in a peer-reviewed journal or book, = 31), grey literature (government or other report or scientific letter, = 18), and opaque literature (non-scientifically indexed reports, care sheets, articles, husbandry books, website or other information for which originating source is not based on scientific evidence or where scientific evidence was not provided, = 16). We found that recommendations suggesting enclosure sizes shorter than the snakes were based entirely on decades-old 'rule of thumb' practices that were unsupported by scientific evidence. In contrast, recommendations suggesting enclosure sizes that allowed snakes to fully stretch utilized scientific evidence and considerations of animal welfare. Providing snakes with enclosures that enable them to fully stretch does not suggest that so doing allows adequate space for all necessary normal and important considerations. However, such enclosures are vital to allow for a limited number of essential welfare-associated behaviors, of which rectilinear posturing is one, making them absolute minimum facilities even for short-term housing

Health system readiness and the implementation of rectal artesunate for severe malaria in sub-Saharan Africa: an analysis of real-world costs and constraints

BACKGROUND: Rectal artesunate, an efficacious pre-referral treatment for severe malaria in children, was deployed at scale in Uganda, Nigeria, and DR Congo. In addition to distributing rectal artesunate, implementation required additional investments in crucial but neglected components in the care for severe malaria. We examined the real-world costs and constraints to rectal artesunate implementation. METHODS: We collected primary data on baseline health system constraints and subsequent rectal artesunate implementation expenditures. We calculated the equivalent annual cost of rectal artesunate implementation per child younger than 5 years at risk of severe malaria, from a health system perspective, separating neglected routine health system components from incremental costs of rectal artesunate introduction. FINDINGS: The largest baseline constraints were irregular health worker supervisions, inadequate referral facility worker training, and inadequate malaria commodity supplies. Health worker training and behaviour change campaigns were the largest startup costs, while supervision and supply chain management accounted for most annual routine costs. The equivalent annual costs of preparing the health system for managing severe malaria with rectal artesunate were US$2.63,$2.20, and $4.19 per child at risk and$322, $219, and$464 per child treated in Uganda, Nigeria, and DR Congo, respectively. Strengthening the neglected, routine health system components accounted for the majority of these costs at 71.5%, 65.4%, and 76.4% of per-child costs, respectively. Incremental rectal artesunate costs accounted for the minority remainder. INTERPRETATION: Although rectal artesunate has been touted as a cost-effective pre-referral treatment for severe malaria in children, its real-world potential is limited by weak and under-financed health system components. Scaling up rectal artesunate or other interventions relying on community health-care providers only makes sense alongside additional, essential health system investments sustained over the long term. FUNDING: Unitaid. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Effectiveness of rectal artesunate as pre-referral treatment for severe malaria in children under 5 years of age: a multi-country observational study

BACKGROUND: To prevent child deaths from severe malaria, early parenteral treatment is essential. Yet, in remote rural areas, accessing facilities offering parenteral antimalarials may be difficult. A randomised controlled trial found pre-referral treatment with rectal artesunate (RAS) to reduce deaths and disability in children who arrived at a referral facility with delay. This study examined the effectiveness of pre-referral RAS treatment implemented through routine procedures of established community-based health care systems. METHODS: An observational study accompanied the roll-out of RAS in the Democratic Republic of the Congo (DRC), Nigeria and Uganda. Children <5 years of age presenting to a community-based health provider with a positive malaria test and signs of severe malaria were enrolled and followed up during admission and after 28 days to assess their health status and treatment history. The primary outcome was death; covariates of interest included RAS use, referral completion, and post-referral treatment. RESULTS: Post-roll-out, RAS was administered to 88% of patients in DRC, 52% in Nigeria, and 70% in Uganda. The overall case fatality rate (CFR) was 6.7% (135/2011) in DRC, 11.7% (69/589) in Nigeria, and 0.5% (19/3686) in Uganda; 13.8% (865/6286) of patients were sick on day 28. The CFR was higher after RAS roll-out in Nigeria (16.1 vs. 4.2%) and stable in DRC (6.7 vs. 6.6%) and Uganda (0.7 vs. 0.3%). In DRC and Nigeria, children receiving RAS were more likely to die than those not receiving RAS (aOR=3.06, 95% CI 1.35-6.92 and aOR=2.16, 95% CI 1.11-4.21, respectively). Only in Uganda, RAS users were less likely to be dead or sick at follow-up (aOR=0.60, 95% CI 0.45-0.79). Post-referral parenteral antimalarials plus oral artemisinin-based combination therapy (ACT), a proxy for appropriate post-referral treatment, was protective. However, in referral health facilities, ACT was not consistently administered after parenteral treatment (DRC 68.4%, Nigeria 0%, Uganda 70.9%). CONCLUSIONS: Implemented at scale to the recommended target group, pre-referral RAS had no beneficial effect on child survival in three highly malaria-endemic settings. RAS is unlikely to reduce malaria deaths unless health system issues such as referral and quality of care at all levels are addressed. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov : NCT03568344

Healing of surgical site after total hip and knee replacements show similar telethermographic patterns

BACKGROUND: Isolated reports indicate the efficacy of infrared thermography for monitoring wound healing and septic complications, but no long-term analysis has ever been performed on this, and there are no data on the telethermographic patterns of surgical site healing after uncomplicated total hip prosthesis and after knee prosthesis. MATERIALS AND METHODS: In this prospective, observational, nonrandomized cohort study, two groups with forty consecutive patients each, who were operated on respectively for total hip and for total knee replacements, underwent telethermographic examination of the operated and contralateral joints prior to and at fixed intervals for up to 1\ua0year after uncomplicated surgery. A digital, portable telethermocamera and dedicated software were used for data acquisition and processing. RESULTS: No thermographic difference was observed preoperatively between the affected side and the contralateral side in both groups. After the intervention, a steep increase in the temperature of the operated joint was recorded after total hip replacement and after knee replacement, with a peak mean differential temperature measured three days postoperatively between the operated and unoperated joint of 3.1\ua0\ub1\ua00.8\ub0C after total hip replacement, and 3.4\ua0\ub1\ua00.7\ub0C after total knee replacement. Thereafter, the mean differential temperature declined slowly to 0.7\ua0\ub1\ua01.1\ub0C and to 0.5\ua0\ub1\ua01.3\ub0C at 60\ua0days, and to 0.0\ua0\ub1\ua01.0\ub0C and -0.1\ua0\ub1\ua01.1\ub0C 90\ua0days post-operatively, respectively. No further changes were observed for up to 1\ua0year after surgery. Results were similar when comparing the average telethermographic values of an elliptical area where the main axis corresponded to the surgical wound. CONCLUSIONS: The surgical sites after uncomplicated total hip or total knee replacement show similar telethermographic patterns for up to 1\ua0year from surgery, and can easily be monitored using a portable, digital, telethermocamera