Parental education and inequalities in child mortality: a global systematic review and meta-analysis.

BACKGROUND: The educational attainment of parents, particularly mothers, has been associated with lower levels of child mortality, yet there is no consensus on the magnitude of this relationship globally. We aimed to estimate the total reductions in under-5 mortality that are associated with increased maternal and paternal education, during distinct age intervals. METHODS: This study is a comprehensive global systematic review and meta-analysis of all existing studies of the effects of parental education on neonatal, infant, and under-5 child mortality, combined with primary analyses of Demographic and Health Survey (DHS) data. The literature search of seven databases (CINAHL, Embase, MEDLINE, PsycINFO, PubMed, Scopus, and Web of Science) was done between Jan 23 and Feb 8, 2019, and updated on Jan 7, 2021, with no language or publication date restrictions. Teams of independent reviewers assessed each record for its inclusion of individual-level data on parental education and child mortality and excluded articles on the basis of study design and availability of relevant statistics. Full-text screening was done in 15 languages. Data extracted from these studies were combined with primary microdata from the DHS for meta-analyses relating maternal or paternal education with mortality at six age intervals: 0-27 days, 1-11 months, 1-4 years, 0-4 years, 0-11 months, and 1 month to 4 years. Novel mixed-effects meta-regression models were implemented to address heterogeneity in referent and exposure measures among the studies and to adjust for study-level covariates (wealth or income, partner's years of schooling, and sex of the child). This study was registered with PROSPERO (CRD42020141731). FINDINGS: The systematic review returned 5339 unique records, yielding 186 included studies after exclusions. DHS data were compiled from 114 unique surveys, capturing 3 112 474 livebirths. Data extracted from the systematic review were synthesized together with primary DHS data, for meta-analysis on a total of 300 studies from 92 countries. Both increased maternal and paternal education showed a dose-response relationship linked to reduced under-5 mortality, with maternal education emerging as a stronger predictor. We observed a reduction in under-5 mortality of 31·0% (95% CI 29·0-32·6) for children born to mothers with 12 years of education (ie, completed secondary education) and 17·3% (15·0-18·8) for children born to fathers with 12 years of education, compared with those born to a parent with no education. We also showed that a single additional year of schooling was, on average, associated with a reduction in under-5 mortality of 3·04% (2·82-3·23) for maternal education and 1·57% (1·35-1·72) for paternal education. The association between higher parental education and lower child mortality was significant for both parents at all ages studied and was largest after the first month of life. The meta-analysis framework incorporated uncertainty associated with each individual effect size into the model fitting process, in an effort to decrease the risk of bias introduced by study design and quality. INTERPRETATION: To our knowledge, this study is the first effort to systematically quantify the transgenerational importance of education for child survival at the global level. The results showed that lower maternal and paternal education are both risk factors for child mortality, even after controlling for other markers of family socioeconomic status. This study provides robust evidence for universal quality education as a mechanism to achieve the Sustainable Development Goal target 3.2 of reducing neonatal and child mortality. FUNDING: Research Council of Norway, Bill & Melinda Gates Foundation, and Rockefeller Foundation-Boston University Commission on Social Determinants, Data, and Decision Making (3-D Commission).

Educational disparities in disability-free life expectancy across Europe: A focus on the East-West gaps from a gender perspective.

Education plays a crucial role in shaping the health outcomes of adults. This study examines the relationship between educational attainment and health across Europe. Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE), we estimate educational inequalities in disability-free life expectancy (DFLE) by gender in seven Western European (2004-2019) and three Central and Eastern European (CEE) (2010-2019) countries. We exploit a novel approach that combines the Sullivan method and multivariate life tables to calculate DFLE using SHARE data. We find that educational differences in DFLE favoring the better-educated exist in both CEE and Western European countries, but also that the differences across countries are more pronounced among the low-educated. While the absolute gaps in DFLE between low- and high-educated individuals in CEE and Western European countries are similar, the educational disparities in DFLE impose a more significant burden on the CEE populations due to their overall lower life expectancy. Educational inequalities are larger among women than among men in CEE countries, while the results for Western European countries are mixed. Our findings further highlight the important role of the institutional context in mitigating or exacerbating educational inequalities in health.

Which public health interventions are effective in reducing morbidity, mortality and health inequalities from infectious diseases amongst children in low- and middle-income countries (LMICs): An umbrella review.

Despite significant progress in the last few decades, infectious diseases remain a major threat to child health in low- and middle-income countries (LMICs)-particularly amongst more disadvantaged groups. It is imperative to understand the best available evidence concerning which public health interventions reduce morbidity, mortality and health inequalities in children aged under five years. To address this gap, we carried out an umbrella review (a systematic reviews of reviews) to identify evidence on the effects of public health interventions (promotion, protection, prevention) on morbidity, mortality and/or health inequalities due to infectious diseases amongst children in LMICs. Ten databases were searched for records published between 2014-2021 alongside a manual search of gray literature. Articles were quality-assessed using the Assessment of Multiple Systematic Reviews tool (AMSTAR 2). A narrative synthesis was conducted. We identified 60 systematic reviews synthesizing 453 individual primary studies. A majority of the reviews reported on preventive interventions (n = 48), with a minority on promotion (n = 17) and almost no reviews covering health protection interventions (n = 2). Effective interventions for improving child health across the whole population, as well as the most disadvantaged included communication, education and social mobilization for specific preventive services or tools, such as immunization or bed nets. For all other interventions, the effects were either unclear, unknown or detrimental, either at the overall population level or regarding health inequalities. We found few reviews reporting health inequalities information and the quality of the evidence base was generally low. Our umbrella review identified some prevention interventions that might be useful in reducing under five mortality from infectious diseases in LMICs, particularly amongst the most disadvantaged groups.

Assessment of the stability of citrate-buffered flucloxacillin for injection when stored in two commercially available ambulatory elastomeric devices: INfusor LV (Baxter) and Accufuser (Woo Young Medical): a study compliant with the NHS Yellow Cover Document (YCD) requirements.

Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD. Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices. Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles.

Investigation of meropenem stability after reconstitution: the influence of buffering and challenges to meet the NHS Yellow Cover Document compliance for continuous infusions in an outpatient setting.

Objectives: To determine the influence of different buffers, pH and meropenem concentrations on the degradation rates of meropenem in aqueous solution during storage at 32°C, with the aim of developing a formulation suitable for 24-hour infusion in an ambulatory elastomeric device, compliant with the latest National Health Service Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: Meropenem was diluted to 6.25 mg/mL and 25 mg/mL in aqueous solutions adjusted to various pH with phosphate or citrate buffer and assessed for stability. Meropenem concentrations were determined using a validated stability-indicating high-performance liquid chromatography method at time 0 and following storage for up to 24 hours at 32°C as per the YCD requirements. Results: Degradation was observed to be slowest in citrate buffer around pH 7 and at a meropenem concentration of 6.25 mg/mL; however, losses exceeded 10% after storage for 24 hours at 32°C in all of the diluents tested in the study. Conclusions: Meropenem at concentrations between 6.25 mg/mL and 25 mg/mL as tested is not sufficiently stable to administer as a 24-hour infusion in ambulatory device reservoirs. If the YCD 95% minimum content limit is applied, the infusion period must be reduced to less than 6 hours for body-worn devices, especially at the higher concentration studied (25 mg/mL). This limits the possibility of using elastomeric devices to deliver continuous infusions of meropenem as part of a wider outpatient parenteral antimicrobial therapy service.

Which public health interventions are effective in reducing morbidity, mortality and health inequalities from infectious diseases amongst children in low-income and middle-income countries (LMICs): protocol for an umbrella review.

INTRODUCTION: Despite significant progress in the last few decades, infectious diseases remain a significant threat to children's health in low-income and middle-income countries. Effective means of prevention and control for these diseases exist, making any differences in the burden of these diseases between population groups or countries inequitable. Yet, gaps remain in our knowledge of the effect these public health interventions have on health inequalities in children, especially in low-income and middle-income countries. This umbrella review aims to address some of these gaps by exploring which public health interventions are effective in reducing morbidity, mortality and health inequalities from infectious diseases among children in low-income and middle-income countries. METHODS AND ANALYSIS: An umbrella review will be conducted to identify systematic reviews or evidence synthesis of public health interventions that reduce morbidity, mortality and/or health inequalities due to infectious diseases among children (aged under 5 years) in low-income and middle-income countries. The interventions of interest are public health interventions targeting infectious diseases or associated risk factors in children. We will search for reviews reporting health and health inequalities outcomes in and between populations. The literature search will be undertaken using the Cochrane Library, Medline, EMBASE, the CAB Global Health database, Health Evidence, the Campbell Collaboration Library of Systematic Reviews, International Initiative for Impact Evaluation Systematic review repository, Scopus, the Social Sciences Citation Index and PROSPERO. Additionally, a manual search will be performed in Google Scholar and three international organisations websites (UNICEF Office of Research-Innocenti, UNICEF, WHO) to capture grey literature. Data from the records meeting our inclusion/exclusion criteria will be collated using a narrative synthesis approach. ETHICS AND DISSEMINATION: This review will exclusively work with anonymous group-level information available from published reviews. No ethical approval was required.The results of the review will be submitted for publication in academic journals and presented at international public health conferences. Additionally, key findings will be summarised for dissemination to a wider policy and general public audience as part of the Centre for Global Health Inequalities Research's policy work. PROSPERO REGISTRATION NUMBER: CRD42019141673.

Performance testing protocol for closed-system transfer devices used during pharmacy compounding and administration of hazardous drugs.

OBJECTIVES: The United States National Institute for Occupational Safety and Health (NIOSH) is developing a protocol to assess the containment performance of closed system transfer devices (CSTDs) when used for drug preparation (task 1) and administration (task 2) and published a draft protocol in September 2016. Nine possible surrogates were proposed by NIOSH for use in the testing. The objectives of this study were to: (A) select the most appropriate surrogate; (B) validate the NIOSH protocol using this surrogate; and (C) determine the containment performance of four commercial CSTDs as compared with an open system of needle and syringe using the validated NIOSH protocol. METHODS: 2-Phenoxyethanol (2-POE) was selected as a surrogate based on its water solubility, Henry's volatility constant, detectability by mass spectrometry, and non-toxicity. Standard analytical validation methods including system suitability, limit of detection (LOD), and limit of quantitation (LOQ) as well as system cleaning validation were performed. The amount of 2-POE released when the CSTDs were manipulated according to two tasks defined by NIOSH was determined using mass spectrometry coupled to thermal desorption and gas chromatography. This approach allows sensitivity of detection below 1 part per billion (ppb). Equashield, Tevadaptor (OnGuard), PhaSeal, and ChemoClave were assessed according to manufacturers' instructions for use. RESULTS: 2-POE was tested and validated for suitability of use within the NIOSH protocol. A simple and efficient cleaning protocol achieved consistently low background values, with an average value, based on 85 measurements, of 0.12 ppb with a 95% confidence interval (CI) of ±0.16 ppb. This gives an LOD for the tests of 0.35 ppb and an LOQ of 0.88 ppb. The Equashield, Tevadaptor (OnGuard), and PhaSeal devices all showed average releases, based on 10 measurements from five tests, that were less than the LOQ (i.e. < 0.88 ppb), while the ChemoClave Vial Shield with Spinning Spiros showed average releases of 2.9±2.3 ppb and 7.5±17.9 ppb for NIOSH tasks 1 and 2 respectively at the 95% confidence level. The open system of needle and syringe showed releases, based on two measurements from a single test, of 4.2±2.2 ppb and 5.1±1.7 ppb for NIOSH tasks 1 and 2 respectively at the 95% confidence level. CONCLUSIONS: 2-POE proved to be an ideal surrogate for testing of CSTDs using the NIOSH protocol. We propose that a CSTD can be qualified using the NIOSH testing approach if the experimental LOQ is less than 1 ppb and the release values are below the LOQ. Equashield, Tevadaptor (OnGuard), and PhaSeal meet these acceptance criteria and can therefore all be qualified as CSTDs, but the ChemoClave system does not and so would not qualify as a CSTD.