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Background: Left unabated, rising temperatures pose an escalating threat to human health. The potential effects of hot temperatures on fetal health have been under-explored. Here, we examined the association between prenatal ambient temperature exposure and fetal growth measures in a Massachusetts-based pregnancy cohort., Methods: We used ultrasound measurements of biparietal diameter (BPD), head circumference (HC), femur length and abdominal circumference (AC), in addition to birthweight (BW), from 9446 births at Beth Israel Deaconess Medical Center from 2011 to 2016. Ultrasound scans were classified into three distinct gestational periods: 16-23 weeks, 24-31 weeks, 32+ weeks; and z-scores were created for each fetal growth measure using the INTERGROWTH-21st standards. We fitted distributed lag models to estimate the time-varying association between weekly temperature and fetal growth, adjusting for sociodemographic characteristics, seasonal and long-term trends, humidity and particulate matter (PM2.5)., Results: Higher ambient temperature was associated with smaller fetal growth measures. The critical window of exposure appeared to be Weeks 1-20 for ultrasound parameters, and high temperatures throughout pregnancy were important for BW. Associations were strongest for head parameters (BPD and HC) in early to mid-pregnancy, AC late in pregnancy and BW. For example, a 5ºC higher cumulative temperature exposure was associated with a lower mean AC z-score of -0.26 (95% CI: -0.48, -0.04) among 24-31-Week scans, and a lower mean BW z-score of -0.32 (95% CI: -0.51, -0.12)., Conclusion: Higher temperatures were associated with impaired fetal growth. This has major health implications given that extreme temperatures are more common and escalating., (© The Author(s) 2022; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: There is tentative evidence to support the analgesic effect of transcranial direct current stimulation (tDCS) in fibromyalgia (FM), with large variability in the effect size (ES) encountered in different clinical trials. Understanding the source of the variability and exploring how it relates to the clinical results could characterize effective neuromodulation protocols and ultimately guide care in FM pain. The primary objective of this study was to determine the effect of tDCS in FM pain as compared with sham tDCS. The secondary objective was to explore the relationship of methodology, population, and intervention factors and the analgesic effect of tDCS in FM., Materials and Methods: For the primary objective, a systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized clinical trials (RCTs) investigating tDCS as an intervention for FM pain were searched in MEDLINE, Embase, and the Web Of Science. Studies were excluded if they used cross-over designs or if they did not use tDCS as an intervention for pain or did not measure clinical pain. Analysis for the main outcome was performed using a random-effects model. Risk of bias and evidence certainty were assessed for all studies using Cochrane Risk of Bias and Grading of Recommendations Assessment, Development, and Evaluation tools. For the secondary objective, a meta-regression was conducted to explore methodology, population, and intervention factors potentially related to the ES., Results: Sixteen RCTs were included. Six studies presented a high risk of bias. Significant reduction in pain scores were found for FM (standardized mean difference = 1.22, 95% CI = 0.80-1.65, p < 0.001). Subgroup analysis considering tDCS as a neural target revealed no differences between common neural sites. Meta-regression revealed that the duration of the tDCS protocol in weeks was the only factor associated with the ES, in which protocols that lasted four weeks or longer reported larger ES than shorter protocols., Conclusions: Results suggest an analgesic effect of tDCS in FM. tDCS protocols that last four weeks or more may be associated with larger ESs. Definite conclusions are inadequate given the large heterogeneity and limited quality of evidence of the included studies., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Preterm birth defined as delivery before 37 gestational weeks, is a leading cause of neonatal and infant morbidity and mortality. Understanding its multifactorial nature may improve prediction, prevention and the clinical management. We performed an umbrella review to summarize the evidence from meta-analyses of observational studies on risks factors associated with PTB, evaluate whether there are indications of biases in this literature and identify which of the previously reported associations are supported by robust evidence. We included 1511 primary studies providing data on 170 associations, covering a wide range of comorbid diseases, obstetric and medical history, drugs, exposure to environmental agents, infections and vaccines. Only seven risk factors provided robust evidence. The results from synthesis of observational studies suggests that sleep quality and mental health, risk factors with robust evidence should be routinely screened in clinical practice, should be tested in large randomized trial. Identification of risk factors with robust evidence will promote the development and training of prediction models that could improve public health, in a way that offers new perspectives in health professionals.

Introduction: Trauma patients with blunt abdominal solid organ injuries are at high risk for venous thromboembolism (VTE), but the optimal time to safely administer chemical thromboprophylaxis is controversial, especially for patients who are managed nonoperatively due to increased risk of hemorrhage. We sought to compare failure of nonoperative management (NOM) and VTE events based on timing of chemical thromboprophylaxis initiation., Methods: A systematic review was conducted in PubMed and Embase databases. Studies were included if they evaluated timing of initiation of chemical thromboprophylaxis in trauma patients who underwent NOM of blunt solid organ injuries. Outcomes included failure of NOM and incidence of VTE. A random-effects meta-analysis was performed comparing patients who received late (>48 h) versus early thromboprophylaxis initiation., Results: Twelve retrospective cohort studies, comprising 21,909 patients, were included. Three studies, including 6375 patients, provided data on adjusted outcomes. Pooled adjusted analysis demonstrated no difference in failure of NOM in patients receiving late versus early thromboprophylaxis (odds ratio [OR] 0.92, 95% confidence interval [CI]:0.4-2.14). When including all unadjusted studies, even those at high risk of bias, there remained no difference in failure of NOM (OR 1.16, 95% CI:0.72-1.86). In the adjusted analysis for VTE events, which had 6259 patients between two studies, patients receiving late chemical thromboprophylaxis had a higher risk of VTE compared with those who received early thromboprophylaxis (OR 1.89, 95% CI:1.15-3.12)., Conclusions: Based on current observational evidence, initiation of prophylaxis before 48 h is associated with lower VTE rates without higher risk of failure of NOM., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines highlighted some concerns about the randomized clinical trials (RCTs) comparing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) for aortic stenosis. Quantification of these biases has not been previously performed., Objective: To assess whether randomization protects RCTs comparing TAVI and SAVR from biases other than nonrandom allocation., Data Sources: A systematic review of the literature between January 1, 2007, and June 6, 2022, on MEDLINE, Embase, and Cochrane Central Register of Controlled Trials was performed. Specialist websites were also checked for unpublished data., Study Selection: The study included RCTs with random allocation to TAVI or SAVR with a maximum 5-year follow-up., Data Extraction and Synthesis: Data extraction was performed by 2 independent investigators following the PRISMA guidelines. A random-effects meta-analysis was used for quantifying pooled rates and differential rates between treatments of deviation from random assigned treatment (DAT), loss to follow-up, and receipt of additional treatments., Main Outcomes and Measures: The primary outcomes were the proportion of DAT, loss to follow-up, and patients who were provided additional treatments and myocardial revascularization, together with their ratio between treatments. The measures were the pooled overall proportion of the primary outcomes and the risk ratio (RR) in the TAVI vs SAVR groups., Results: The search identified 8 eligible trials including 8849 participants randomly assigned to undergo TAVI (n = 4458) or SAVR (n = 4391). The pooled proportion of DAT among the sample was 4.2% (95% CI, 3.0%-5.6%), favoring TAVI (pooled RR vs SAVR, 0.16; 95% CI, 0.08-0.36; P < .001). The pooled proportion of loss to follow-up was 4.8% (95% CI, 2.7%-7.3%). Meta-regression showed a significant association between the proportion of participants lost to follow-up and follow-up time (slope, 0.042; 95% CI, 0.017-0.066; P < .001). There was an imbalance of loss to follow-up favoring TAVI (RR, 0.39; 95% CI, 0.28-0.55; P < .001). The pooled proportion of patients who had additional procedures was 10.4% (95% CI, 4.4%-18.5%): 4.6% (95% CI, 1.5%-9.3%) in the TAVI group and 16.5% (95% CI, 7.5%-28.1%) in the SAVR group (RR, 0.27; 95% CI, 0.15-0.50; P < .001). The imbalance between groups also favored TAVI for additional myocardial revascularization (RR, 0.40; 95% CI, 0.24-0.68; P < .001)., Conclusions and Relevance: This study suggests that, in RCTs comparing TAVI vs SAVR, there are substantial proportions of DAT, loss to follow-up, and additional procedures together with systematic selective imbalance in the same direction characterized by significantly lower proportions of patients undergoing TAVI that might affect internal validity.

Exposure to ambient temperature has been linked to adverse birth outcomes in several regions, including the USA, Australia, China, countries in the Middle East, and European countries. To date, no studies were performed in South America, a region with serious challenges related to climate change. Our investigation addresses this literature lack by examining the association between Low Birth Weight (LBW) and ambient temperature exposure in the largest county in South America, Brazil. We applied a nationwide case-control study design using a logistic regression model to estimate the odds ratio (OR) for LBW associated with ambient temperature during a specific trimester of pregnancy (1-3 trimester). Our sample size includes 5,790,713 birth records nationwide over 18 years (2001-2018), of which 264,967 infants were included in the model as cases of LBW, representing 4.6% of our total sample. We adjusted our model for several confounding variables, including weather factors, air pollution, seasonality, and SES variables at the individual level. Our findings indicate that North was the only region with positive and statistically significant associations in the primary analysis and most of the sensitivity analysis, which is the region where the Amazon is located. In this region, we estimated an increase of 5.16% (95%CI: 3.60; 6.74) in the odds of LBW per 1 °C increase in apparent temperature when the exposure occurred in the second trimester. Our results may be explained by the climate conditions in the Amazon region in the past years. A large body of literature indicates that the Amazon region has been facing serious climate challenges including issues related to policy, governance, and deforestation. Specifically, regarding deforestation, it is suggested that land use change and deforestation is projected to increase heat stress in the Amazon region, because of Amazon savannization, increasing the risk of heat stress exposure in Northern Brazil. Our study can assist public sectors and clinicians in mitigating the risk and vulnerability of the Amazonian population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The total mesorectal excision (TME) significantly improved rectal cancer outcomes. Radiotherapy's benefit in T3N0 rectal cancer patients managed with TME has not been clearly demonstrated. A systematic review and meta-analysis were undertaken to determine whether radiotherapy altered the risk of locoregional recurrence (LR) in T3N0 rectal cancer patients managed with a TME., Materials and Methods: Studies indexed on PubMed or Embase were systematically searched from inception to October 18, 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for the literature search, study screening, and data extraction; the Newcastle Ottawa Scale evaluated bias; Grades of Recommendation, Assessment, Development, and Evaluation Working Group system evaluated certainty; and all were performed independently by at least two investigators. Studies that reported LR data specific to T3N0 rectal cancer patients managed with TME, treated with and without radiotherapy, were included. Data was pooled using a random-effects model. Meta-analyses of the relative risk of local recurrence were conducted., Results: Five retrospective cohort studies involving 932 unique patients reported LR outcomes; no prospective studies met eligibility criteria. Median follow-up ranged from 38.4-78 months. Adjuvant radiotherapy was provided in 3 studies. Chemotherapy was delivered and reported in 4 studies, providing both concurrent and adjuvant chemotherapy. A non-significant LR reduction with radiotherapy alongside TME was estimated, mean relative risk (RR) 0.63 (95% Confidence Interval 0.31-1.29; I 2 = 41.8%)., Conclusions: A non-significant LR benefit with radiotherapy's addition was estimated. Meta-analysis of exclusively retrospective cohort studies was concerning for biased results. Adequately powered randomized trials are warranted.

The evidence for use of direct oral anticoagulants (DOACs) in the management of post-operative cardiac surgery atrial fibrillation is limited and mostly founded on clinical trials that excluded this patient population. We performed a systematic review and meta-analysis of clinical trials and observational studies to evaluate the hypothesis that DOACs are safe compared to warfarin for the anticoagulation of patients with post-operative cardiac surgery atrial fibrillation. We searched PubMed, EMBASE, Web of Science, clinicaltrials.gov, and the Cochrane Library for clinical trials and observational studies comparing DOAC with warfarin in patients ≥18 years old who had post-cardiac surgery atrial fibrillation. Primary outcomes included stroke, systemic embolization, bleeding, and mortality. We performed a random-effects meta-analysis of all outcomes. The meta-analysis for the primary outcomes showed significantly lower risk of stroke with DOAC use (6 studies, 7143 patients, RR 0.64; 95% CI 0.50-0.81, I 2 : 0.0%) compared to warfarin, a trend towards lower risk of systemic embolization (4 studies, 7289 patients, RR 0.64, 95% CI 0.41-1.01, I 2 : 31.99%) and similar risks of bleeding (14 studies, 10182 patients, RR 0.91; 95% CI 0.74-1.10, I 2 : 26.6%) and mortality (12 studies, 9843 patients, relative risk [RR] 1.01; 95% CI 0.74-1.37, I 2 : 26.5%). Current evidence suggests that DOACs, compared to warfarin, in the management of atrial fibrillation after cardiac surgery is associated with lower risk of stroke and a strong trend for lower risk of systemic embolization, and no evidence of increased risk for hospital readmission, bleeding and mortality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Birth defects are a major cause of poor health outcomes during both childhood and adulthood. A growing body of evidence demonstrated associations between air pollution exposure during pregnancy and birth defects. To date, there is no study looking at birth defects and exposure to wildfire-related air pollution, which is suggested as a type of air pollution source with high toxicity for reproductive health., Objective: Our study addresses this gap by examining the association between birth defects and wildfire smoke exposure in Brazil between 2001 and 2018. Based on known differences of impacts of wildfires across different regions of Brazil, we hypothesized differences in risks of birth defects for different regions., Methods: We used a logistic regression model to estimate the odds ratios (ORs) for individual birth defects (12 categories) associated with wildfire exposure during each trimester of pregnancy., Results: Among the 16,825,497 birth records in our study population, there were a total of 7595 infants born in Brazil between 2001 and 2018 with birth defects in any of the selected categories. After adjusting for several confounders in the primary analysis, we found statistically significant OR for three birth defects, including cleft lip/cleft palate [OR: 1.007 (95% CI: 1.001; 1.013)] during the second trimester of exposure, congenital anomalies of the respiratory system [OR: 1.013 (95% CI: 1.002; 1.023)] in the second trimester of exposure, and congenital anomalies of the nervous system [OR: 1.002 (95% CI: 1.001; 1.003)] during the first trimester of exposure for the regions South, North, and Midwest, respectively., Significance: Our results suggest that maternal exposure to wildfire smoke during pregnancy may increase the risk of an infant being born with some congenital anomaly. Considering that birth defects are associated with long-term disability, impacting families and the healthcare system (e.g., healthcare costs), our findings should be of great concern to the public health community., Impact Statement: Our study focused on the association between maternal exposure to wildfire smoke in Brazil during pregnancy and the risk of an infant being born with congenital anomalies, which presents serious public health and environmental challenges., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Introduction: Incarcerated populations represent a vulnerable and marginalised segment of society, with increased health needs and a higher burden of communicable and non-communicable diseases. Traditional population health outcomes do not capture physical, mental, emotional and social well-being. Health-related quality of life (HRQoL) outcomes attempt to measure these important parameters. To date, there has not been a scoping review to summarise the HRQoL literature in the incarcerated population. Thus, we aim to perform such a review to inform health policy decisions in incarcerated populations and support health economic evaluations of interventions in incarcerated populations., Methods and Analysis: We will conduct a scoping review of the literature on the HRQoL in the incarcerated population informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the corresponding PRISMA Extension for Scoping Reviews. The submissions records of six electronic databases with peer-reviewed literature and three health technology assessment agencies will be searched. The search strategy was informed by recommendations for HRQoL reviews. We will include studies that report HRQoL, health state utility values or reference to quality adjusted life years or quality-adjusted life expectancies of incarcerated populations. No assessments of items' quality will be made, as the purpose of this scoping review is to synthesise and describe the coverage of the evidence. We will also identify knowledge gaps on the HRQoL in the incarcerated population., Ethics and Dissemination: Research ethics approval is not required as primary data will not be collected. The findings of this scoping review will be used to inform health economic analyses for the incarcerated population and will be disseminated through peer-reviewed publications and conference presentations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The optimal method of coronary revascularization for diabetes mellitus (DM) patients with left main coronary artery disease (LMCAD) is controversial in the drug-eluting stent (DES) era., Methods: We performed a systematic review and meta-analysis comparing DES-based percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) for LMCAD in DM patients and tested for effect measure modification (EMM) by diabetes for adverse events. We included all randomized controlled trials (RCTs) and observational studies comparing CABG to DES-based PCI including DM patients with LMCAD published up to March 1, 2021. We completed separate random-effects meta-analyses for four RCTs (4356 patients, mean follow-up of 4.9 years) and six observational studies (9360 patients, mean follow-up of 5.2 years)., Results: In RCTs among DM patients, DES-based PCI, compared to CABG, was associated with a 30% increased relative risk (RR) (RR 1.30, 95% CI 1.09-1.56, I 2  = 0%), while among non-DM patients, there was a 25% increased relative risk (RR 1.25, 95% CI 1.07-1.44, I 2  = 0%) for the composite endpoint of all-cause mortality, myocardial infarction, stroke, and unplanned revascularization (MACCE). There was no evidence of EMM (p-value for interaction = 0.70). The mean weighted SYNTAX score was 25.7. In observational studies, there was no difference between DES-based PCI and CABG for all-cause mortality in patients with DM (RR 1.13, 95% CI 0.91-1.40, I 2  = 0%)., Conclusions: CABG was superior to PCI for LMCAD in RCTs in DM patients for MACCE. Heart teams may consider DM as one of the many components in the clinical decision-making process, but may not want to consider DM as a primary deciding factor between DES-based PCI and CABG for LMCAD with low to intermediate anatomical complexity in the other coronary arteries., Study Registration: CRD42021246931 (PROSPERO)., (© 2022. The Author(s).)

Preterm birth (PTB) complications are the leading cause of death among children under 5 years of age, responsible for approximately 1 million deaths in 2015, according to the World Health Organization. Those infants born prematurely who survived the first 5 years, studies suggest that these infants are more likely to experience a range of poor health outcomes during childhood and even adulthood. Wildfire smoke has been suggested as a type of air pollution source with high toxicity for reproductive health. In this study, we estimated the association between preterm birth and wildfire periods in Brazil, a country included in the list of the 10 nations with the greatest number of preterm birth and also considered as a very fire-prone region. We applied a time-stratified case-crossover study design using conditional logistic regression models to estimate the odds ratio for preterm birth associated with wildfire-related prenatal PM 2.5 , during different windows of exposure, including trimesters 1-3. After adjusting for several confounders (other air pollutants, demographics, meteorological variables, and spatiotemporal terms), we found that wildfire smoke exposure during pregnancy may be associated with preterm birth in Brazil. Southeast was the region with the highest increase in the odds of PTB (OR:1.41 (95%CI: 1.31-1.51) when the exposure occurred in the first trimester. In the North, exposure to PM 2.5 during wildfire periods in the second trimester of pregnancy was associated with increased odds of PTB (OR:1.05 (95%CI: 1.01-1.09) in preterm birth when the exposure occurred in the second trimester. This study suggests that wildfire smoke exposure during pregnancy may increase the risk for preterm birth in Brazil. This should be of great concern to the public health authorities, obstetricians, and policymakers., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

Purpose: Omentin-1 plays an important role in regulating insulin sensitivity outside pregnancy. As an adipokine derived from human placental and adipose tissue, it may be an important contributor in the biological pathway of gestational diabetes., Methods: Omentin-1 was measured in a sub-cohort of 50 participants in the Omega study. We aimed to evaluate whether circulating maternal omentin-1 concentrations are associated with fasting serum glucose, insulin, HOMA-IR and maternal obesity as measured by body mass index (BMI) and subcutaneous and intra-abdominal fat thickness measurements in normoglycemic pregnant participants. We performed a subgroup analysis by BMI category., Results: Omentin-1 was negatively correlated with HOMA-IR and insulin and inversely associated with serum glucose concentration in the fully adjusted model (- 47%; slope per tertile increase in concentration - 0.19; P-trend 0.01). This association was significant in non-overweight/obese (< 25 kg/m 2 ) but not among overweight/obese (≥ 25 kg/ m 2 ) participants. The association with serum insulin was not significant in the fully adjusted model., Conclusion: Circulating omentin-1 concentrations are inversely associated with serum glucose concentrations. Although the relevance of these findings remains to be elucidated, they may indicate a mechanism for the development of insulin resistance and gestational diabetes. Follow-up studies with larger sample sizes are warranted., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Prior studies have examined the association between fine particulate matter [PM ≤ 2.5 μ m in aerodynamic diameter ( PM 2.5 )] and fetal growth with either limited spatial or temporal resolution., Objectives: In this study, we examined the association between PM 2.5 exposure during pregnancy and fetal growth measures (ultrasound parameters and birth weight) in a pregnancy cohort using spatiotemporally resolved PM 2.5 in Eastern Massachusetts, USA., Methods: We used ultrasound measures of biparietal diameter (BPD), head circumference, femur length, and abdominal circumference (AC), in addition to birth weight, from 9,446 pregnancies that were delivered at the Beth Israel Deaconess Medical Center from 2011-2016. We used linear mixed-effects models to examine the associations of PM 2.5 in two exposure windows (the first 16 wk of pregnancy and the cumulative exposure up until the assessment of fetal growth) with anatomic scans (ultrasound measures at < 24   wk ), growth scans (ultrasound measures at ≥ 24 wk ), and birth weight. All models were adjusted for sociodemographic characteristics, long-term trends, and temperature., Results: Higher PM 2.5 exposure in the first 16 wk was associated with smaller fetal growth measures, where associations were particularly strong for BPD, AC, and birth weight. For example, a 5 - μ g / m 3 increase in PM 2.5 was associated with a lower mean BPD z -score of - 0.19 (95% CI: - 0.31 , - 0.06 ) before 24 wk, a lower mean AC z -score of - 0.15 (95% CI: - 0.28 , - 0.01 ) after 24 wk, and a lower mean birth weight z -score of - 0.11 (95% CI: - 0.20 , - 0.01 ). Analyses examining the associations with cumulative PM 2.5 exposure up until the assessment of fetal growth produced attenuated associations., Conclusions: Higher gestational exposure to PM 2.5 was associated with smaller fetal growth measures at levels below the current national standards. https://doi.org/10.1289/EHP9824.

Background: Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of respiratory complications. It is unclear whether administration at term gestations, prior to caesarean section, improves the respiratory outcomes for these babies without causing any unnecessary morbidity to the mother or the infant., Objectives: The objective of this review was to assess the effect of prophylactic corticosteroid administration before elective caesarean section at term, as compared to usual care (which could be placebo or no treatment), on fetal, neonatal and maternal morbidity. We also assessed the impact of the treatment on the child in later life., Search Methods: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov (20 January 2021) and reference lists of retrieved studies., Selection Criteria: We included randomised controlled trials comparing prophylactic antenatal corticosteroid administration (betamethasone or dexamethasone) with placebo or with no treatment, given before elective caesarean section at term (at or after 37 weeks of gestation). Quasi-randomised and cluster-randomised controlled trials were also eligible for inclusion., Data Collection and Analysis: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness (based on predefined criteria developed by Cochrane Pregnancy and Childbirth), extracted data and checked them for accuracy and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were respiratory distress syndrome (RDS), transient tachypnoea of the neonate (TTN), admission to neonatal special care for respiratory morbidity and need for mechanical ventilation. We planned to perform subgroup analyses for the primary outcomes according to gestational age at randomisation and type of corticosteroid (betamethasone or dexamethasone). We also planned to perform sensitivity analysis, including only studies at low risk of bias., Main Results: We included one trial in which participants were randomised to receive either betamethasone or usual care. The trial included 942 women and 942 neonates recruited from 10 UK hospitals between 1995 and 2002. This review includes only trials that met predefined criteria for trustworthiness. We removed three trials from the analysis that were included in the previous version of this review. The risk of bias was low for random sequence generation, allocation concealment and incomplete outcome data. The risk of bias for selective outcome reporting was unclear because there was no published trial protocol, and therefore it is unclear whether all the planned outcomes were reported in full. Due to a lack of blinding we judged there to be high risk of performance bias and detection bias. We downgraded the certainty of the evidence because of concerns about risk of bias and because of imprecision due to low event rates and wide 95% confidence intervals (CIs), which are consistent with possible benefit and possible harm Compared with usual care, it is uncertain if antenatal corticosteroids reduce the risk of RDS (relative risk (RR) 0.34 95% CI 0.07 to 1.65; 1 study; 942 infants) or TTN (RR 0.52, 95% CI 0.25 to 1.11; 1 study; 938 infants) because the certainty of evidence is low and the 95% CIs are consistent with possible benefit and possible harm. Antenatal corticosteroids probably reduce the risk of admission to neonatal special care for respiratory complications, compared with usual care (RR 0.45, 95% CI 0.22 to 0.90; 1 study; 942 infants; moderate-certainty evidence). The proportion of infants admitted to neonatal special care for respiratory morbidity after treatment with antenatal corticosteroids was 2.3% compared with 5.1% in the usual care group. It is uncertain if antenatal steroids have any effect on the risk of needing mechanical ventilation, compared with usual care (RR 4.07, 95% CI 0.46 to 36.27; 1 study; 942 infants; very low-certainty evidence). The effect of antenatal corticosteroids on the maternal development of postpartum infection/pyrexia in the first 72 hours is unclear due to the very low certainty of the evidence; one study (942 women) reported zero cases. The included studies did not report any data for neonatal hypoglycaemia or maternal mortality/severe mortality., Authors' Conclusions: Evidence from one randomised controlled trial suggests that prophylactic corticosteroids before elective caesarean section at term probably reduces admission to the neonatal intensive care unit for respiratory morbidity. It is uncertain if administration of antenatal corticosteroids reduces the rates of respiratory distress syndrome (RDS) or transient tachypnoea of the neonate (TTN). The overall certainty of the evidence for the primary outcomes was found to be low or very low, apart from the outcome of admission to neonatal special care (all levels) for respiratory morbidity, for which the evidence was of moderate certainty. Therefore, there is currently insufficient data to draw any firm conclusions.  More evidence is needed to investigate the effect of prophylactic antenatal corticosteroids on the incidence of recognised respiratory morbidity such as RDS. Any future trials should assess the balance between respiratory benefit and potential immediate adverse effects (e.g. hypoglycaemia) and long-term adverse effects (e.g. academic performance) for the infant. There is very limited information on maternal health outcomes to provide any assurances that corticosteroids do not pose any increased risk of harm to the mother.  Further research should consider investigating the effectiveness of antenatal steroids at different gestational ages prior to caesarean section. There are nine potentially eligible studies that are currently ongoing and could be included in future updates of this review., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Mounting evidence has shown that long-term exposure to fine particulate matter [PM ≤ 2.5 μ m in aerodynamic diameter ( PM 2.5 )] and ozone ( O 3 ) can increase mortality. However, the health effects associated with long-term exposure to nitrogen dioxide ( NO 2 ) are less clear, in particular the evidence is scarce for NO 2 at low levels that are below the current international guidelines., Methods: We constructed a population-based full cohort comprising all Medicare beneficiaries (aged ≥ 65 , N = 13,590,387 ) in the southeastern United States from 2000 to 2016, and we then further defined the below-guideline cohort that included only those who were always exposed to low-level NO 2 , that is, with annual means below the current World Health Organization guidelines (i.e., ≤ 21  ppb ). We applied previously estimated spatially and temporally resolved NO 2 concentrations and assigned annual means to study participants based on their ZIP code of residence. Cox proportional hazards models were used to examine the association between long-term exposure to low-level NO 2 and all-cause mortality, adjusting for potential confounders., Results: About 71.1% of the Medicare beneficiaries in the southeastern United States were always exposed to low-level NO 2 over the study period. We observed an association between long-term exposure to low-level NO 2 and all-cause mortality, with a hazard ratio  ( HR ) = 1.042 (95% CI: 1.040, 1.045) in single-pollutant models and a HR = 1.047 (95% CI: 1.045, 1.049) in multipollutant models (adjusting for PM 2.5 and O 3 ), per 10 -ppb increase in annual NO 2 concentrations. The penalized spline indicates a linear exposure-response relationship across the entire NO 2 exposure range. Medicare enrollees who were White, female, and residing in urban areas were more vulnerable to long-term NO 2 exposure., Conclusion: Using a large and representative cohort, we provide epidemiological evidence that long-term exposure to NO 2 , even below the national and global ambient air quality guidelines, was approximately linearly associated with a higher risk of mortality among older adults, independent of PM 2.5 and O 3 exposure. Improving air quality by reducing NO 2 emissions, therefore, may yield significant health benefits. https://doi.org/10.1289/EHP9044.

Background: Ambient air pollution has been characterized as a leading cause of mortality worldwide and has been associated with cardiovascular and respiratory diseases. There is increasing evidence that short-term exposure to nitrogen dioxide (NO 2 ), is related to adverse health effects and mortality., Methods: We conducted a systematic review of short-term NO 2 and daily mortality, which were indexed in PubMed and Embase up to June 2021. We calculated random-effects estimates by different continents and globally, and tested for heterogeneity and publication bias., Results: We included 87 articles in our quantitative analysis. NO 2 and all-cause as well as cause-specific mortality were positively associated in the main analysis. For all-cause mortality, a 10 ppb increase in NO 2 was associated with a 1.58% (95%CI 1.28%-1.88%, I 2  = 96.3%, Eggers' test p < 0.01, N = 57) increase in the risk of death. For cause-specific mortality, a 10 ppb increase in NO 2 was associated with a 1.72% (95%CI 1.41%-2.04%, I 2  = 87.4%, Eggers' test p < 0.01, N = 42) increase in cardiovascular mortality and a 2.05% (95%CI 1.52%-2.59%, I 2  = 78.5%, Eggers' test p < 0.01, N = 38) increase in respiratory mortality. In the sensitivity analysis, the meta-estimates for all-cause mortality, cardiovascular and respiratory mortality were nearly identical. The heterogeneity would decline to varying degrees through regional and study-design stratification., Conclusions: This study provides evidence of an association between short-term exposure to NO 2 , a proxy for traffic-sourced air pollutants, and all-cause, cardiovascular and respiratory mortality., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To compare the mortality associated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS)., Methods: We searched publications from PubMed, Embase, Web of Science, and the Cochrane Library from inception until December 23, 2020. All randomized clinical trials (RCTs) and observational studies comparing all-cause mortality after treatment with CABG versus PCI for patients with NSTE-ACS with minimum follow-up of 6 months were included. Restricted mean survival time (RMST) differences from RCTs and adjusted RMST differences from observational studies were computed by reconstructing time-to-event data from published Kaplan-Meier curves. Extracted hazard ratios (HRs) were also assessed as a secondary analysis., Results: Our systematic review included an individual participant data analysis of 3 RCTs and 8 observational studies. A meta-regression showed a significant association between log-transformed HRs and duration of follow-up (-0.009 [95% confidence interval (CI), -0.002 to -0.016] log-HR per 1-year longer follow-up; P  = .037), suggesting a violation of the proportional hazard assumption. Analysis of 6 studies with available RMST data showed a significant inverse association between adjusted RMST differences and cutoff years (slope, -0.028 [95% CI, -0.042 to -0.013] year difference per 1-year longer cutoff; P  < .005), suggesting a longer survival benefit in the CABG arm compared with the PCI arm with longer follow-up., Conclusions: There was a trend toward a benefit of CABG compared with PCI in the longer follow-up in patients with NSTE-ACS. A large, well-designed RCT with longer follow-up is needed to obtain definitive evidence on this topic., (© 2021 The Author(s).)

Background: Ambient air pollution is among the greatest environmental risks to human health. However, little is known about the health effects of nitrogen dioxide (NO 2 ), a traffic-related air pollutant. Herein, we aimed to conduct a meta-analysis to investigate the long-term effects of NO 2 on mortality., Methods: We conducted a systematic search for studies that were published up to February 2020 and performed a meta-analysis of all available epidemiologic studies evaluating the associations between long-term exposure to NO 2 with all-cause, cardiovascular, and respiratory mortality. Overall pooled effect estimates as well as subgroup-specific pooled estimates (e.g. location, exposure assessment method, exposure metric, study population, age at recruitment, and key confounder adjustment) and 95% confidence intervals were calculated using random-effects models. Risk of bias assessment was accessed by following WHO global air quality guidelines. Publication bias was accessed by visually inspecting funnel plot and Egger's liner regression was used to test of asymmetry., Results: Our search initially retrieved 1349 unique studies, of which 34 studies met the inclusion criteria. The pooled hazard ratio (HR) for all-cause mortality was 1.06 (95%CI: 1.04-1.08, n = 28 studies, I 2  = 98.6%) per 10 ppb increase in annual NO 2 concentrations. The pooled HRs for cardiovascular and respiratory mortality per 10 ppb increment were 1.11 (95%CI: 1.07-1.16, n = 20 studies, I 2  = 99.2%) and 1.05 (95%CI: 1.02-1.08, n = 17 studies, I 2  = 94.6%), respectively. The sensitivity analysis pooling estimates from multi-pollutant models suggest an independent effect of NO 2 on mortality. Funnel plots indicate that there is no evidence for publication bias in our study., Conclusion: We provide robust epidemiological evidence that long-term exposure to NO 2 , a proxy for traffic-sourced air pollutants, is associated with a higher risk of all-cause, cardiovascular, and respiratory mortality that might be independent of other common air pollutants., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2021. Published by Elsevier B.V.)

Background: Exposure to ionizing radiation has been associated with insulin resistance and type 2 diabetes. In light of recent work showing an association between ambient particulate matter (PM) gross β-activity and gestational diabetes mellitus (GDM) among pregnant women, we examined pregnancy glucose levels in relation to PM gross β-activity to better understand this pathway., Methods: Our study included 103 participants receiving prenatal care at Beth Israel Deaconess Medical Center in Boston, MA. PM gross β-activity was obtained from US Environmental Protection Agency's RadNet program monitors, and blood glucose levels were obtained from the non-fasting glucose challenge test performed clinically as the first step of the 2-step GDM screening test. For each exposure window we examined (i.e., moving average same-day, one-week, first-trimester, and second-trimester PM gross β-activity), we fitted generalized additive models and adjusted for clinical characteristics, socio-demographic factors, temporal variables, and PM with an aerodynamic diameter ≤ 2.5 μm (PM 2.5 ). Subgroup analyses by maternal age and by body mass index were also conducted., Results: An interquartile range increase in average PM gross β-activity during the second trimester of pregnancy was associated with an increase of 17.5 (95% CI: 0.8, 34.3) mg/dL in glucose concentration. Associations were stronger among younger and overweight/obese participants. Our findings also suggest that the highest compared to the lowest quartile of one-week exposure was associated with 17.0 (95% CI: - 4.0, 38.0) mg/dL higher glucose levels. No associations of glucose were observed with PM gross β-activity during same-day and first-trimester exposure windows. PM 2.5 was not associated with glucose levels during any exposure window in our data., Conclusions: Exposure to higher levels of ambient PM gross β-activity was associated with higher blood glucose levels in pregnant patients, with implications for how this novel environmental factor could impact pregnancy health.

Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety, and efficacy for these procedures in different clinical scenarios. The objective of the present study was to pool the available evidence to compare outcomes among patients with hydrocephalus undergoing ETV versus VPS. A systematic search of the literature was conducted via PubMed, EMBASE, and Cochrane Library through 11/29/2018 to identify studies evaluating failure and complication rates, following ETV or VPS. Pooled effect estimates were calculated using random effects. Heterogeneity was assessed by the Cochrane Q test and the I 2 value. Heterogeneity sources were explored through subgroup analyses and meta-regression. Twenty-three studies (five randomized control trials (RCTs) and 18 observational studies) were meta-analyzed. Comparing ETV to VPS, failure rate was not statistically significantly different with a pooled relative risk (RR) of 1.48, 95%CI (0.85, 2.59) for RCTs and 1.17 (0.89, 1.53) for cohort studies; P-interaction: 0.44. Complication rates were not statistically significantly different between ETV and VPS in RCTs (RR: 1.34, 95%CI: 0.50, 3.59) but were statistically significant for prospective cohort studies (RR: 0.47, 95%CI: 0.30, 0.78); P-interaction: 0.07. Length of hospital stay was no different, when comparing ETV and VPS. These results remained unchanged when stratifying by intervention type and when regressing on age when possible. No significant differences in failure rate were observed between ETV and VPS. ETV was found to have lower complication rates than VPS in prospective cohort studies but not in RCTs. Further research is needed to identify the specific patient populations who may be better suited for one intervention versus another.

Inhaling radon and its progeny is associated with adverse health outcomes. However, previous studies of the health effects of residential exposure to radon in the United States were commonly based on a county-level temporally invariant radon model that was developed using measurements collected in the mid- to late 1980s. We developed a machine learning model to predict monthly radon concentrations for each ZIP Code Tabulation Area (ZCTA) in the Greater Boston area based on 363,783 short-term measurements by Spruce Environmental Technologies, Inc., during the period 2005-2018. A two-stage ensemble-based model was developed to predict radon concentrations for all ZCTAs and months. Stage one included 12 base statistical models that independently predicted ZCTA-level radon concentrations based on geological, architectural, socioeconomic, and meteorological factors for each ZCTA. Stage two aggregated the predictions of these 12 base models using an ensemble learning method. The results of a 10-fold cross-validation showed that the stage-two model has a good prediction accuracy with a weighted R 2 of 0.63 and root mean square error of 22.6 Bq/m 3 . The community-level time-varying predictions from our model have good predictive precision and accuracy and can be used in future prospective epidemiological studies in the Greater Boston area.

Background: Exposure to ionizing radiation has been associated with hypertension, but the relationship between residential radon exposure and hypertensive disorders of pregnancy (HDP) has not been examined., Methods: We used the Massachusetts Birth Registry of Vital Records from 2001 to 2015 including women with a singleton pregnancy without prior hypertension. The binary outcome (HDP) included gestational hypertension and pre-eclampsia cases and was assessed using birth certificate data. We obtained 141,665 basement radon measurements from Spruce Environmental Technologies, Inc. and modeled the monthly zip code basement radon level. We used a logistic regression model adjusted for sociodemographic covariates, maternal comorbidities, PM 2.5 , season, temperature, and relative humidity. We examined effect modification by maternal age, race, and maternal education as an indicator of socio-economic status., Results: Of 975,528 women, 3.7% (36,530) of them developed HDP. Zip code level radon ranged from 22 to 333 mBq/m 3 . An interquartile range (IQR) increase in zip code radon level throughout pregnancy was associated with a 15% increase in the odds of HDP (95% CI 13% to 18%). In women less than 20 years old, an IQR increase in zip code level radon was associated with 38% increase in the odds of HDP (95% CI 24% to 50%), while the effect was smaller in older women. There was no effect modification by maternal race or education., Conclusions: In this cohort, higher levels of residential radon are associated with increased odds of HDP. After stratifying by age, this effect was stronger in participants younger than 20 years old. Since the burden of hypertensive disorders of pregnancy is increasing and affects women's future cardiovascular health, identification of modifiable risk factors is of great importance., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: While the results of previous meta-analyses have shown beneficial effects of corticosteroid therapy on post-extubation stridor and extubation failure in adults, these results might not be generalizable to children because of the differences in anatomy and structure. We aimed to determine the benefits of corticosteroids on those outcomes in pediatric populations., Methods: We searched PubMed, EMBASE, and reference lists of articles from inception until February 2019. Randomized controlled trials and observational studies on the efficacy of systemic corticosteroid administration given prior to elective extubation in mechanically ventilated pediatrics were eligible. Outcomes included post-extubation stridor indicating laryngeal edema and extubation failures., Results: A total of ten randomized controlled trials with 591 pediatric patients were included: seven of the ten studies for post-extubation stridor/suspected upper airway obstruction and nine of the ten studies for extubation failure. The estimate of pooled odds ratios (ORs) for post-extubation stridor/suspected upper airway obstruction was 0.40 (95% CI: 0.21-0.79). When analysis was restricted to trials that had explicit data for infants and explicit data for pediatric patients under 5 years old excluding infants, the estimates of pooled ORs were 0.53 (95% CI: 0.20-1.40) and 0.68 (95% CI: 0.38-1.22), respectively. For pediatric patients who received corticosteroids, there was a 0.37-fold lower odds of extubation failure than that in pediatric patients who did not receive corticosteroids (OR, 0.37; 95% CI, 0.22-0.61). While three observational studies were included in this review, their estimates have a potential for bias and we did not perform a meta-analysis., Conclusions: Despite a relatively small sample size in each randomized controlled trial and wide ranges of ages and steroid administration regimens, our results suggest that the use of corticosteroids for prevention of post-extubation stridor and extubation failure could be considered to be acceptable in pediatric patients.

Background: The literature suggests an increased risk between anthropometrics including higher body mass index and lymphoma incidence; however, the association with physical activity remains unclear. A systematic review/meta-analysis was therefore performed to examine this association with physical activity (total, recreational or occupational)., Methods: PubMed, Web of Science and Embase were reviewed from inception to October 2019 identifying relevant observational studies. Non-Hodgkin lymphoma (NHL) including subtypes diffuse large B cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, and Hodgkin lymphoma (HL) were analyzed. Included studies reported activity, lymphoma cases, effect size and variability measures, and were restricted to human subjects of any age. Data was pooled generating summary relative risk (RR) estimates with 95% confidence intervals (CI) using random-effects models with primary outcome of histologically confirmed incident lymphoma., Results: One thousand four hundred studies were initially identified with 18 studies (nine cohort, nine case-control) included in final analysis. Comparing highest vs. lowest activity categories was protective for all lymphoma (RR 0.89, 95%CI 0.81-0.98). Sensitivity analysis demonstrated effect persistence within case-control studies (RR 0.82, 95% CI 0.71-0.96), but not cohort studies (RR 0.95, 95%CI 0.84-1.07). Borderline protective effect was seen for NHL (RR 0.92, 95%CI 0.84-1.00), but not HL (RR 0.72, 95%CI 0.50-1.04). Analysis by NHL subtype or gender showed no effect. Dose response analysis demonstrated a protective effect (p = 0.034) with a 1% risk reduction per 3 MET hours/week (RR 0.99, 95%CI 0.98-1.00)., Conclusions: Physical activity may have a protective effect against lymphoma development; further studies are required to generate recommendations regarding health policy., Trial Registration: This study was registered prospectively at PROSPERO: CRD42020156242 .

There is a lack of evidence on causal effects of air pollution on gestational age (GA) at delivery., Methods: Inverse probability weighting (IPW) quantile regression was applied to derive causal marginal population-level GA reduction for GA percentiles associated with increased ambient particulate matter with diameter <2.5 μm (PM 2.5 ) levels at maternal residential address for each trimester and the month preceding delivery using Massachusetts birth registry 2001 to 2015. Stratified analyses were conducted for neonatal sex, maternal age/race/education, and extreme ambient temperature conditions., Results: For neonates at 2.5th, 10th, 25th, 50th, 75th, and 97.5th percentiles of GA at delivery, we estimated an adjusted GA reduction of 4.2 days (95% confidence interval [CI] = 3.4, 5.0), 1.9 days (1.6, 2.1), 1.2 days (1.0, 1.4), 0.82 days (0.72, 0.92), 0.74 days (0.54, 0.94), and 0.54 days (0.15, 0.93) for each 5 μg/m3 increment in third trimester average PM 2.5 levels. Final gestational month average exposure yielded a similar effect with greater magnitude. Male neonates and neonates of younger (younger than 35 years) and African American mothers as well as with high/low extreme temperature exposure in third trimester were more affected. Estimates were consistently higher at lower GA percentiles, indicating preterm/early-term births being more affected. Low-exposure analyses yielded similar results, restricting to areas with PM 2.5 levels under US ambient annual standard of 12 μg/m 3 ., Conclusions: Prenatal exposure to PM 2.5 in late pregnancy reduced GA at delivery among Massachusetts neonates, especially among preterm/early-term births, male neonates, and neonates of younger and African American mothers. Exposure to extremely high/low temperature amplifies the effect of PM 2.5 on GA., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report. This study was supported by the National Institutes of Health (NIH) grant (R01 ES024332-01A1, ES-000002). This publication was made possible also by US Environmental Protection Agency (EPA) grant (RD-835872-01). Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the US EPA. Further, US EPA does not endorse the purchase of any commercial products or services mentioned in the publication. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The funding sources support open access publishing.Sponsorships or competing interests that may be relevant to content are disclosed at the end of the article., (Copyright © 2020 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The Environmental Epidemiology. All rights reserved.)

Background: Exposure to ionizing radiation increases the risk of chronic metabolic disorders such as insulin resistance and type 2 diabetes. Internal ionizing radiation from inhaled radioactive aerosol may contribute to the associations between fine particulate matter (PM 2.5 ) and gestational diabetes mellitus (GDM)., Methods: We used the Massachusetts Registry of Vital Records to study 1,061,937 pregnant women from 2001 to 2015 with a singleton pregnancy without pre-existing diabetes. Gross β activity measured by seven monitors of the U.S. Environmental Protection Agency's RadNet monitoring network was utilized to represent ambient particle radioactivity (PR). We obtained GDM status from birth certificates and used logistic regression analyses adjusted for socio-demographics, maternal comorbidities, PM 2.5 , temperature and relative humidity. We also examined effect modification by smoking habits., Results: Ambient particle radioactivity exposure during first and second trimester of pregnancy was associated with higher odds of GDM (OR: 1.18 (95% CI 1.10 to 1.22). Controlling for PM 2.5 did not substantially change the effects of PR on GDM. In women that reported being former or current smokers, the association between PR and GDM was null. In the full cohort, the overall effect of PM 2.5 on GDM without adjusting for PR was not significant., Conclusion: This is the first population-based study to examine the association between particle radioactivity and gestational diabetes mellitus - one of the most common pregnancy-related diseases with lifelong effects for the mother and the fetus. This finding has important public health policy implications because it enhances our understanding about the toxicity of PR, a modifiable risk factor, which to date, has been considered only as an indoor and occupational air quality risk., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The characteristics of desert dust storms (DDS) have been shown to change in response to climate change and land use. There is limited information on the frequency and intensity of DDS over the last decade at a regional scale in the Eastern Mediterranean. An algorithm based on daily ground measurements (PM 10 , particulate matter ≤10 μm), satellite products (dust aerosol optical depth) and meteorological parameters, was used to identify dust intrusions for three Eastern Mediterranean locations (Crete-Greece, Cyprus, and Israel) between 2006 and 2017. Days with 24-hr average PM 10 concentration above ~30 μg/m 3 were found to be a significant indicator of DDS for the background sites of Cyprus and Crete. Higher thresholds were found for Israel depending on the season (fall and spring: PM 10  > 70 μg/m 3 , winter and summer: PM 10  > 90 μg/m 3 ). We observed a high variability in the frequency and intensity of DDS during the last decade, characterized by a steady trend with sporadic peaks. The years with the highest DDS frequency were not necessarily the years with the most intense episodes. Specifically, the highest dust frequency was observed in 2010 at all three locations, but the highest annual median dust-PM 10 level was observed in 2012 in Crete (55.8 μg/m 3 ) and Israel (137.4 μg/m 3 ), and in 2010 in Cyprus (45.3 μg/m 3 ). Crete and Cyprus experienced the same most intense event in 2006, with 24 h-PM 10 average of 705.7 μg/m 3 and 1254.6 μg/m 3 , respectively, which originated from Sahara desert. The highest 24 h-PM10 average concentration for Israel was observed in 2010 (3210.9 μg/m 3 ) during a three-day Saharan dust episode. However, a sub-analysis for Cyprus (years 2000-2017) suggests a change in DDS seasonality pattern, intensity, and desert of origin. For more robust conclusions on DDS trends in relation to climate change, future work needs to study data over several decades from different locations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background Healthcare-acquired pneumonias are a significant risk for nursing home and hospital patients. While oral care interventions (OCIs) have been found to be effective in reducing the risk of ventilator-associated pneumonia (VAP), their utility in mitigating non-ventilator-associated pneumonias (NVAP) remains unknown. We performed a structured meta-analysis of randomised and non-randomised clinical trials of enhanced oral hygiene procedures on NVAP.Methods We searched PubMed and Embase to include clinical trials (randomised and non-randomised), and observational (retrospective and prospective) and quasi-experimental studies examining the effect of any method of OCI on incidence of NVAP.Results After quality assessment and consensus agreement between authors, we synthesised six randomised clinical trials (3,891 patients), two non-randomised trials (2,993 patients), and separately assessed a retrospective trial (143 patients) and a quasi-experimental study (83 patients). Most studies, performed in nursing homes, did not show a significant association between OCI and NVAP prevention (RR random 0.89, 95% CI 0.64-1.25, p value 0.50). Likewise, the non-randomised trials failed to show an association between NVAP risk and OCI (RR random 1.42, 95% CI, 0.70-2.88, p value 0.32). However, in the subgroup analysis comparing dental professional involvement in care vs usual care, reduced NVAP risk was demonstrated (RR random 0.65, 95% CI 0.43-0.98, p value 0.03).Conclusions Study results suggest that professional dental care may confer some benefit among NVAP patients. The lack of consistent OCI protocols, data in hospitalised patients and robust randomised clinical trials do not allow definitive conclusions about the contribution of OCI in mitigating NVAP risk.

Aims: Idiopathic left ventricular hypertrophy (LVH) is defined as LVH in the absence of myocyte disarray or secondary causes. It is unclear whether idiopathic LVH represents the phenotypic spectrum of hypertrophic cardiomyopathy (HCM) or whether it is a unique disease entity. We aimed to ascertain the prevalence of HCM in first-degree relatives of decedents from sudden death with idiopathic LVH at autopsy. Decedents also underwent molecular autopsy to identify the presence of pathogenic variants in genes implicated in HCM., Methods and Results: Families of 46 decedents with idiopathic LVH (125 first-degree relatives) were investigated with electrocardiogram, echocardiogram exercise tolerance test, cardiovascular magnetic resonance imaging, 24-h Holter, and ajmaline provocation test. Next-generation sequencing molecular autopsy was performed in 14 (30%) cases. Decedents with idiopathic LVH were aged 33 ± 14 years and 40 (87%) were male. Fourteen families (30%) comprising 16 individuals were diagnosed with cardiac disease, including Brugada syndrome (n = 8), long QT syndrome (n = 3), cardiomyopathy (n = 2), and Wolff-Parkinson-White syndrome (n = 1). None of the family members were diagnosed with HCM. Molecular autopsy did not identify any pathogenic or likely pathogenic variants in genes encoding sarcomeric proteins. Two decedents had pathogenic variants associated with long QT syndrome, which were confirmed in relatives with the clinical phenotype. One decedent had a pathogenic variant associated with Danon disease in the absence of any histopathological findings of the condition or clinical phenotype in the family., Conclusion: Idiopathic LVH appears to be a distinct disease entity from HCM and is associated with fatal arrhythmias in individuals with primary arrhythmia syndromes. Family screening in relatives of decedents with idiopathic LVH should be comprehensive and encompass the broader spectrum of inherited cardiac conditions, including channelopathies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Introduction: The role for steroids in acute spinal cord injury (ASCI) remains unclear; while some studies have demonstrated the risks of steroids outweigh the benefits,a meta-analyses conducted on heterogeneous patient populations have shown significant motor improvement at short-term but not at long-term follow-up. Given the heterogeneity of the patient population in previous meta-analyses and the publication of a recent trial not included in these meta-analyses, we sought to re-assess and update the safety and short-term and long-term efficacy of steroid treatment following ASCI in a more homogeneous patient population., Materials and Methods: A literature search was conducted on PubMed, EMBASE and Cochrane Library through June 2019 for studies evaluating the utility of steroids within the first 8 h following ASCI. Neurological and safety outcomes were extracted for patients treated and not treated with steroids. Pooled effect estimates were calculated using the random-effects model., Results: Twelve studies, including five randomized controlled trials (RCTs) and seven observational studies (OBSs), were meta-analyzed. Overall, methylprednisolone was not associated with significant short-term or long-term improvements in motor or neurological scores based on RCTs or OBSs. An increased risk of hyperglycemia was shown in both RCTs (RR: 13.7; 95% CI: 1.93, 97.4; 1 study) and OBSs (RR: 2.9; 95% CI: 1.55, 5.41; 1 study). Risk for pneumonia was increased with steroids; while this increase was not statistically significant in the RCTs (pooled RR: 1.16; 95% C.I: 0.59, 2.29; 3 studies), it reached statistical significance in the OBSs (pooled RR: 2.00; 95% C.I: 1.32, 3.02; 6 studies). There was no statistically significant increased risk of gastrointestinal bleeding, decubitus ulcers, surgical site infections, sepsis, atelectasis, venous thromboembolism, urinary tract infections, or mortality among steroid-treated ASCI patients compared to untreated controls in either RCTs or OBSs., Conclusions: Methylprednisolone therapy within the first 8 h following ASCI failed to show a statistically significant short-term or long-term improvement in patients' overall motor or neurological scores compared to controls who were not administered steroids. For the same comparison, there was an increased risk of pneumonia and hyperglycemia compared to controls. Routine use of methylprednisone following ASCI should be carefully considered in the context of these results., (© 2020 Published by Elsevier Ltd.)

Objective: To evaluate the effects of omega-3 long-chain polyunsaturated fatty acids on proteinuria, estimated glomerular filtration rate (eGFR) and metabolic biomarkers among patients with diabetes., Study Design: Meta-analysis of randomized controlled clinical trials (RCTs)., Setting & Subjects: Patients with diabetes., Selection Criteria for Studies: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to April 2019 to identify RCTs, which examined the effects of omega-3 fatty acids on proteinuria, eGFR and metabolic biomarkers among diabetic patients., Results: Ten RCTs with 344 participants were included in our meta-analysis. Omega-3 fatty acids reduced the amount of proteinuria among type 2 diabetes mellitus (type 2 DM) and type 1 diabetes mellitus (type 1 DM). This association was only significant among type 2 DM (SMD = -0.29 (95% CI: -0.54, -0.03; p = 0.03). Only studies with duration of intervention of 24 weeks or longer demonstrated a significant lower proteinuria among omega-3 fatty acids compared to control group (SMD = -0.30 (95% CI: -0.58, -0.02; p = 0.04). There was a higher eGFR for both type 1 and type 2 DM groups among omega-3 fatty acids compared to control group, however, the effect was not statistically significant. Regarding serum total cholesterol, LDL-cholesterol and HbA1C, there was no significant difference comparing omega-3 fatty acids to control group. There was a non-significant systolic blood pressure reduction in the omega-3 fatty acids supplementation group compared to control., Conclusion: Omega-3 fatty acids could help ameliorate proteinuria among type 2 DM who received omega-3 supplementation for at least 24 weeks without adverse effects on HbA1C, total serum cholesterol and LDL-cholesterol., Competing Interests: No authors have competing interests.

Background and Purpose- Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia. Methods- A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models. Results- These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 [95% CI, 1.06-1.50]). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 [95% CI, 0.74-1.16]) and the presence of microbleeds (odds ratio, 1.13 [95% CI, 0.89-1.44]) were not statistically significant. Conclusions- A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.

This study aimed to evaluate human papillomavirus (HPV)-related knowledge of women aged 18-25 years and estimate the reported uptake of HPV vaccine and testing. A cross-sectional study was conducted among female students of the University of Cyprus between March and April 2017. The participants self-completed a questionnaire, which consisted of 37 items on demographics, general HPV-related knowledge, and HPV vaccination and testing. In total, 283 young females (mean age: 19.7 ± 1.5 years) took part in the study. Of these, about half (53.7%) reported that they were aware of HPV; one-third (30.7%) reported having been vaccinated; 38.8% had been informed of the recent introduction of the HPV vaccine in the National Immunization Schedule in Cyprus, while 14.3% reported a previous Pap-test and 3.4% a previous HPV DNA test. The mean Overall Knowledge Index (max: 25 correct answers) was 6.1 (±3.8) and was positively associated with the reported uptake of the HPV vaccine (adjusted Odds ratio: 1.14, 95% Confidence Interval (CI): 1.04-1.24). Knowledge about HPV has to be improved as it is associated with increased reported rates of HPV vaccination.

Background: The analgesic effects of transcranial Direct Current Stimulation (tDCS) combined with physical therapy remain unclear., Objective: To systematically review available evidence comparing tDCS with any physical therapy modality (PTM) to PTM alone or PTM with sham tDCS on pain relief on common musculoskeletal (MSK) conditions, namely knee osteoarthritis (KOA), chronic low back pain (CLBP), myofascial pain syndrome (MPS) and fibromyalgia., Methods: EMBASE and MEDLINE were searched from inception to April 2019 for randomized controlled trials. Reviewers independently assessed the studies quality and extracted data according to the PRISMA protocol. The GRADE approach was used to asses quality of evidence and a "Summary of Findings" table was created. The analyses used random-effects model. The primary outcome was pain reduction after treatment., Results: Eight articles were included. Only one study had low risk of bias. Quality of evidence was considered low or very low. Significant reduction in pain scores were found for fibromyalgia and KOA (Standardized mean difference (SMD) = -1.94 [95% CI: -3.37 to -0.49; I 2 =76.4%] and SMD = -2.35 [95% CI: -3.63 to -1.06; I 2 =69.7%] respectively). Subgroup analysis considering the type of PTM despite MSK condition revealed significant reduction in pain scores for exercise, SMD = -1.20 [95% CI: -1.683 to -0.717; I 2 =10.8%]., Conclusions: Large heterogeneity and low quality of evidence and limited number of studies were found. Results suggest a potential analgesic effect of tDCS in combination with a PTM for fibromyalgia and KOA. Subgroup analysis suggests a stronger effect of tDCS when combined with an exercise based PTM., Competing Interests: Conflict of Interest The author followed the International Committee of Journal of Medical Journal Editors (ICMJE) form for disclosure of potential conflicts of interest. The listed author concurs with the submission of the manuscript. The final version has been approved by the author. The author has no financial or personal conflicts of interest.

Sudden cardiac death (SCD) is often associated with structural abnormalities of the heart during autopsy. This study sought to compare the diagnostic yield of postmortem genetic testing in (1) cases with structural findings of uncertain significance at autopsy to (2) cases with autopsy findings diagnostic of cardiomyopathy. We evaluated 57 SCD cases with structural findings at cardiac autopsy. Next-generation sequencing using a panel of 77 primary electrical disorder and cardiomyopathy genes was performed. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. In 29 cases (51%) autopsy findings of uncertain significance were identified whereas in 28 cases (49%) a diagnosis of cardiomyopathy was established. We identified a pathogenic or likely pathogenic variant in 10 cases (18%); in 1 (3%) case with non-specific autopsy findings compared with 9 (32%) cases with autopsy findings diagnostic of cardiomyopathy (p = 0.0054). The yield of genetic testing in SCD cases with autopsy findings consistent with cardiomyopathy is comparable with the yield in cardiomyopathy patients that are alive. Genetic testing in cases with findings of uncertain significance offers lower clinical utility than in cardiomyopathy, with lower yields than detected previously. This highlights the need for stringent evaluation of variant pathogenicity.

Objectives: Major spinal corrective surgeries can be associated with critical intra-operative blood loss. The objective of this systematic review and meta-analysis was to assess the safety and efficacy of tranexamic acid (TXA), a commonly used antifibrinolytic agent, in adult spinal deformity (ASD) surgery, defined as fusion of five or more levels., Methods: Articles from PubMed, Embase, Cochrane, and clinicaltrials.gov were screened using PRISMA guidelines through December 2018. Thromboembolic events, blood loss, and transfusion levels were primary outcomes of interest. Randomized controlled trials (RCTs) and observational studies (OBSs) with adult patients (≥ 18 years) were included. Continuous variables were analyzed using mean difference (MD) and categorical variables were analyzed using Peto odds ratio (OR), via random effects models., Results: Of the 604 articles screened, seven studies (two RCTs and five cohort studies) were included. Incidence of thromboembolic events was not statistically significantly different between TXA (1 event/19) and placebo (0 events/13) in the RCT (Peto OR = 1.41, 95% CI 0.05-37.2; 32 patients; 1 study) and in the OBSs (TXA [2 events/135] vs control [0 events/72]; Peto OR = 1.09, 95% CI 0.16-7.61; p-heterogeneity = 0.85; 207 patients; 3 studies). Data from OBSs showed that the pooled MD was statistically significantly lower in the TXA group compared with the control group for intraoperative blood loss (MD: - 620.2 mL, 95% CI - 1066.6 to - 173.7; p-heterogeneity = 0.14; 228 patients; 4 studies) and total transfusion volume (MD: - 958.2 mL, 95% CI - 1867.5 to - 49.0; p-heterogeneity = 0.23; 93 patients; 2 studies)., Conclusion: In this meta-analysis, TXA was not significantly associated with increased risk of thromboembolic events but was associated with lower intraoperative blood loss and lower total transfusion volumes in ASD surgery.

Background: The prevalence of spinal deformities increases with age, affecting between 30% and 68% of the elderly population (ages ≥65). The reported prevalence of complications associated with surgery for spinal deformities in this population ranges between 37% and 71%. Given the wide range of reported complication rates, the decision to perform surgery remains controversial., Methods: A comprehensive search was conducted using PubMed, Embase, and Cochrane to identify studies reporting complications for spinal deformity surgery in the elderly population. Pooled prevalence estimates for individual complication types were calculated using the random-effects model., Results: Of 5,586 articles, 14 met inclusion criteria. Fourteen complication types were reported, with at least 2 studies for each complication with the following pooled prevalence: reoperation (prevalence 19%; 95% CI, 9-36%; 107 patients); hardware failure (11%; 95% CI, 5-25%; 52 patients); infection (7%; 95% CI, 4-12%; 262 patients); pseudarthrosis (6%; 95% CI, 3-12%; 149 patients); radiculopathy (6%; 95% CI, 1-33%; 116 patients); cardiovascular event (5%; 95% CI, 1-32%; 121 patients); neurological deficit (5%; 95% CI, 2-15%; 248 patients); deep vein thrombosis (3%; 95% CI, 1-7%; 230 patients); pulmonary embolism (3%; 95% CI, 1-7%; 210 patients); pneumonia (3%; 95% CI, 1-11%; 210 patients); cerebrovascular or stroke event (2%; 95% CI, 0-9%; 85 patients); death (2%; 95% CI, 1-9%; 113 patients); myocardial infarction (2%; 95% CI, 1-6%; 210 patients); and postoperative hemorrhage (1%; 95% CI, 0-10%; 85 patients)., Conclusions: Most complication types following spinal deformity surgery in the elderly had prevalence point estimates of <6%, while all were at least ≤19%. Additional studies are needed to further explore composite prevalence estimates and prevalence associated with traditional surgical approaches as compared to minimally-invasive procedures in the elderly., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background and Purpose- Digital subtraction angiography has been used as the gold standard to confirm successful aneurysmal obliteration after aneurysm clipping procedures using titanium or cobalt alloy clips. Computed tomographic angiography is a newer, less invasive imaging technique also used to confirm successful aneurysmal obliteration; however, its use compared with digital subtraction angiography remains controversial. Methods- A comprehensive literature search was conducted on Pubmed, EMBASE, and Cochrane databases through November 6, 2017, for studies that evaluated postclipping aneurysm obliteration with both computed tomographic angiography and digital subtraction angiography. Pooled sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated using the bivariate random-effects model. Results- Out of 6916 studies, 13 studies met inclusion criteria for this meta-analysis. A total of 510 patients with 613 aneurysms were included. Compared with digital subtraction angiography, which detected 87 residual aneurysms, computed tomographic angiography detected 58 resulting in a pooled sensitivity of 69% (95% CI, 54%-81%) and a pooled specificity of 99% (95% CI, 97%-99%). This corresponded to LR+ of 55.5 (95% CI, 23.6-130.9) and LR- of 0.31 (95% CI, 0.20-0.48). Univariate meta-regression revealed that the pooled sensitivity was worse in prospective designs ( P interaction <0.05), and the pooled specificity was better in higher-quality studies and for postoperative aneurysm diameters of <2 mm ( P interaction <0.001 for both). Conclusions- This meta-analysis revealed that computed tomographic angiography had a favorable LR+ but not a favorable LR-. Thus, this imaging modality may be applicable to rule in, but not rule out, residual aneurysms after clipping.

Aim: To synthesize magnetic nanoparticles loaded with the SGLT2-inhibitor canagliflozin (CANA) and evaluate its anticancer potential under normoxic and hypoxic conditions in combination or not with radiotherapy., Material & Methods: Iron oxide nanoparticles were synthesized via an alkaline hydrolytic precipitation of iron precursor in the presence of poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate). CANA was conjugated to the nanoparticles using N-ethyl-N'-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide chemistry. The anticancer efficacy of the nanoparticles was evaluated in cancer cell lines and in a mouse PDV C57 tumor model., Results: In the mouse xenograft cancer model, the combination of CANA-loaded nanoparticles with radiotherapy (in the presence of an external magnetic field at the tumor site) exhibited higher antitumor activity compared with the combination of free CANA with radiotherapy., Conclusion: The results obtained indicate the potential that the combination of selective delivery of a SGLT2 inhibitor such as CANA with radiotherapy holds as an anticancer treatment.

Background: Infants born at term by elective caesarean section are more likely to develop respiratory morbidity than infants born vaginally. Prophylactic corticosteroids in singleton preterm pregnancies accelerate lung maturation and reduce the incidence of respiratory complications., Objectives: The objective of this review was to assess the effect of prophylactic corticosteroid administration before elective caesarean section at term, as compared to usual management without corticosteroids, in reducing neonatal respiratory morbidity and admission to special care with respiratory complications., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (14 June 2017), and reference lists of retrieved studies., Selection Criteria: Randomised controlled trials comparing prophylactic antenatal corticosteroid administration (betamethasone or dexamethasone) with placebo or with no treatment, given before elective caesarean section at term (at or after 37 weeks of gestation)., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach., Main Results: We included four trials (3956 women and 3893 neonates) at a moderate risk of bias, comparing prophylactic administration of betamethasone or dexamethasone versus placebo or usual treatment without steroids in term elective caesarean section. Women randomised to treatment group received either two intramuscular doses of betamethasone in the 48 hours before delivery, or intramuscular dexamethasone (two or four doses) prior to delivery (at 37 weeks' gestation or 48 hours before delivery), and were compared to the control group who received a saline placebo or treatment as usual.Prophylactic antenatal corticosteroid administration appeared to decrease the risk of respiratory distress syndrome (RDS) (risk ratio (RR) 0.48; 95% confidence interval (CI) 0.27 to 0.87; 4 studies; 3817 participants; low-quality evidence), transient tachypnoea of the neonate (TTN) (RR 0.43; 95% CI 0.29 to 0.65; 4 studies; 3821 participants; low-quality evidence), admission to the neonatal intensive care unit (NICU) for respiratory morbidity (RR 0.42; 95% CI 0.22 to 0.79; 3 studies; 3441 participants), and admission to neonatal special care (all levels) for respiratory complications (RR 0.45; 95% CI 0.22 to 0.90; 1 study; 942 participants; low-quality evidence). Administration of antenatal corticosteroids also appeared to reduce admission to neonatal special care (RR 0.62; 95% CI 0.43 to 0.89; 2 studies; 2169 participants) and neonatal intensive care (RR 0.14; 95% CI 0.03 to 0.61; 1 study; 452 participants) for any indication, compared to placebo or usual care. Finally, prophylactic antenatal corticosteroids also appeared to reduce the length of stay in NICU by 2.70 days (mean difference (MD) -2.70; 95% CI -2.76 to -2.64; 2 studies; 32 participants).No reduction was found in the need for mechanical ventilation (RR 0.67; 95% CI 0.27 to 1.68; 3 studies; 3441 participants; very-low quality), perinatal death (RR 0.67; 95% CI 0.11 to 4.10; 4 studies; 3893 participants) or neonatal sepsis (RR 1.00; 95% CI 0.06 to 15.95; 2 studies; 2214 participants) .There were no reported events of neonatal respiratory complications (other than RDS and tachypnoea of the newborn (TTN)), chronic lung disease, duration of mechanical ventilation or maternal postpartum infection, therefore results on these outcomes are non-estimable. The studies did not provide data on other pre-defined outcomes.The quality of evidence, as assessed using GRADE was low for the outcomes of RDS, TTN and admission to NICU for respiratory morbidity, indicating that the true effect could potentially be substantially different from our estimate of effect., Authors' Conclusions: The results from the four trials are promising, but more high-quality studies with larger sample sizes that are adequately powered to detect the effect of prophylactic antenatal corticosteroids on outcomes of respiratory morbidity are needed, given the potential of the current studies for bias. Consideration should be given to the balance between statistical significance and clinical significance, particularly in view of the low event rates of significant respiratory morbidity (RDS or admission to NICU for respiratory complications) in this population. In addition, further trials on the long-term outcomes of these infants are needed to identify any potential harms and complications of antenatal corticosteroid administration at term.

Background: The association between athletic participation and alteration in diastolic function is not well established. The aims of this study were to determine the spectrum of Doppler parameters of left ventricular (LV) diastolic function in a large cohort of healthy athletes and to quantify the overlap between physiologic LV hypertrophy and hypertrophic cardiomyopathy (HCM)., Methods: A retrospective analysis of indices of LV diastolic function was performed in 1,510 healthy athletes (mean age, 22 ± 5 years; range, 13-33 years; 72% men). The results were compared with those from 58 young patients with HCM., Results: Septal E' < 7 cm/sec and lateral E' < 10 cm/sec were found in five (0.3%) and eight (0.5%) athletes, respectively. Septal E' was >14.6 cm/sec in 170 (11%) and lateral E' was >19.9 cm/sec in 430 (28%) athletes. Athletes aged >25 years showed lower E' velocities compared with younger athletes (mean septal E', 11.8 ± 6.1 vs 12.9 ± 5.9 cm/sec [P < .001]; mean lateral E', 17.1 ± 3.6 vs 19.3 ± 4.1 cm/sec [P < .001]). Athletes with high indexed LV end-diastolic diameters (>32 mm/m 2 ) exhibited lower septal E' compared with athletes with normal indexed LV end-diastolic diameters (mean septal E', 11.9 ± 6 vs 12.7 ± 6 cm/sec; P = .002). Septal E' < 10 cm/sec and lateral E' < 12 cm/sec showed the best accuracy in differentiating between HCM and athlete's heart., Conclusions: Reduced septal and lateral E' are rarely observed in young elite athletes. Tissue Doppler velocities tend to decrease with increasing age and LV size, and values representative of supernormal diastolic function are found in less than one-third of young athletes. Cutoff thresholds for Doppler parameters of diastolic function should be corrected for multiple demographic and clinical variables to differentiate cardiac adaptation to exercise from HCM in young individuals., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the health risks of air pollution and cardiorespiratory diseases, globally, across regions and populations, which may differ because of external factors., Objectives: We systematically reviewed the evidence on the association between air pollution and cardiorespiratory diseases (hospital admissions and mortality), including variability by energy, transportation, socioeconomic status, and air quality., Search Methods: We conducted a literature search (PubMed and Web of Science) for studies published between 2006 and May 11, 2016., Selection Criteria: We included studies if they met all of the following criteria: (1) considered at least 1 of these air pollutants: carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, or particulate matter (PM 2.5 or PM 10 ); (2) reported risk for hospital admissions, mortality, or both; (3) presented individual results for respiratory diseases, cardiovascular diseases, or both; (4) considered the age groups younger than 5 years, older than 65 years, or all ages; and (5) did not segregate the analysis by gender., Data Collection and Analysis: We extracted data from each study, including location, health outcome, and risk estimates. We performed a meta-analysis to estimate the overall effect and to account for both within- and between-study heterogeneity. Then, we applied a model selection (least absolute shrinkage and selection operator) to assess the modifier variables, and, lastly, we performed meta-regression analyses to evaluate the modifier variables contributing to heterogeneity among studies., Main Results: We assessed 2183 studies, of which we selected 529 for in-depth review, and 70 articles fulfilled our study inclusion criteria. The 70 studies selected for meta-analysis encompass more than 30 million events across 28 countries. We found positive associations between cardiorespiratory diseases and different air pollutants. For example, when we considered only the association between PM 2.5 and respiratory diseases ( Figure 1 , we observed a risk equal to 2.7% (95% confidence interval = 0.9%, 7.7%). Our results showed statistical significance in the test of moderators for all pollutants, suggesting that the modifier variables influence the average cardiorespiratory disease risk and may explain the varying effects of air pollution., Conclusions: Variables related to aspects of energy, transportation, and socioeconomic status may explain the varying effect size of the association between air pollution and cardiorespiratory diseases. Public Health Implications. Our study provides a transferable model to estimate the health effects of air pollutants to support the creation of environmental health public policies for national and international intervention.

Objective: To systematically review and integrate data on the neurodevelopmental outcome of children after administration of a single course of antenatal corticosteroids for threatened preterm labor., Data Sources: MEDLINE, Scopus, CENTRAL, and www.clinicaltrials.gov (inception to August 2014) using combinations of the terms "prenatal," "antenatal," "cortico*," "*steroid*," "betamethasone," "dexamethasone," "neurodevelopment*," "*development*," and "follow-up." We perused the references of the retrieved articles., Methods of Study Selection: We included randomized and nonrandomized trials reporting on the neurodevelopmental outcomes of children whose mothers were administered a single course of betamethasone or dexamethasone antenatally for threatened preterm birth as opposed to placebo or no treatment., Tabulation, Integration, and Results: Summary risk ratio (RR) was calculated for dichotomous data; standardized mean difference was calculated for trials that measured the same outcome but used different methods. Heterogeneity was assessed using the I statistic. Sensitivity and subgroup analyses were planned according to study design, specific steroid, and mean gestational age at birth. A single course of antenatal corticosteroids was associated with reduced risk for cerebral palsy (seven studies; treated: 390 of 5,199, untreated: 146 of 1,379; RR 0.678, 95% confidence interval [CI] 0.564-0.815), psychomotor development index less than 70 (two studies; treated: 783 of 3,049, untreated: 258 of 969; RR 0.829, 95% CI 0.737-0.933), and severe disability (five studies; treated: 1,567 of 4,840, untreated: 475 of 1,211; RR 0.787, 95% CI 0.729-0.850). Steroid treatment increased the rates of intact survival (six studies; treated: 1,082 of 2,013, untreated: 273 of 561; RR 1.186, 95% CI 1.056-1.332). Betamethasone was found to significantly decrease the risk for severe disability and increase the rate of intact survival. Dexamethasone increased the rate of intact survival; however, data for dexametasone and the other planned subgroup analyses were limited (fewer than 1,000 children at most). The major limitations involved inclusion of nonrandomized studies and scarcity of data on finer neurodevelopmental outcomes., Conclusion: A single course of antenatal corticosteroids in women at high risk for preterm birth appears to improve most neurodevelopmental outcomes in offspring born before 34 weeks of gestation.

Background: Heart defects are the most common congenital abnormalities., Objective: We aimed to evaluate in a meta-analysis the screening performance of abnormal ductus venosus (DV) Doppler waveform for detection of congenital heart disease (CHD) in chromosomally normal fetuses., Search Strategy: Studies were retrieved from a search of MEDLINE, ISI, SCOPUS and EMBASE (from 1999 to March 2011) using the keywords 'ductus venosus', 'DV', 'chromosomal abnormalities', 'congenital heart disease' and 'nuchal translucency'., Selection Criteria: We considered all studies that examined the diagnostic performance of DV in the first trimester for CHD in chromosomally normal fetuses. We included studies that were limited to fetuses with increased nuchal translucency (NT), normal NT, and studies that examined fetuses regardless of NT status., Data Collection and Analysis: Seven studies (n = 50,354) regardless of the NT status, nine studies (n = 2908) with increased NT and seven studies (n = 47,610) with normal NT were included in the meta-analysis. We drew hierarchical summary receiver operating characteristic (HSROC) curves using the parameters of the fitted models., Main Results: In populations including participants regardless of NT status, the summary sensitivity and specificity of DV for detecting CHD were 50 and 93%, respectively. In participants with increased NT, the summary sensitivity and specificity were 83 and 80%, and in those with normal NT, they were 19 and 96%, respectively., Authors' Conclusions: The estimated performance of DV assessment for detection of CHD in chromosomally normal fetuses can be considered in evaluating the potential use and limitations of this screening test., (© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)

Objective: To report a case of a healthy woman who was admitted to the hospital with septic shock caused by a common uropathogen after self-administration of misoprostol for pregnancy termination., Design: Case report., Setting: Tertiary hospital., Patient(s): A 38-year-old woman, gravida 5, para 3, who developed septic shock after medical termination of pregnancy., Intervention(s): Suction curettage, antibiotic treatment, plasma and platelet transfusions., Main Outcome Measure(s): Klebsiella pneumoniae was isolated from blood samples., Result: Ten days after her admission she was discharged home in good condition on oral antibiotics., Conclusion(s): Severe infections leading to septic shock from common pathogen bacteria can occur after medical termination of pregnancy, independently of the regimen used., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the predictive performance of cervical length measurement at presentation and 24h later in women with symptoms of preterm labour., Study Design: Cervical length was measured transvaginally at presentation and 24 hours later in 122 women presenting with threatened preterm labour between 23 and 33+6 gestational weeks., Results: Six women delivered within 1 week of presentation. The sensitivity and specificity of a cervical length <15 mm at admission for delivery within one week was 83.3 and 95.8%, respectively. A reduction of >20% in cervical length 24h after admission predicted 50% of preterm deliveries within 1 week, with a specificity of 92.7%; in combination with cervical length at presentation it did not improve the prediction. The same was observed for birth before 32 weeks (N=9) and birth before 35 weeks (N=15)., Conclusions: Women with threatened preterm labour and a cervical length of <15 mm at presentation are at high risk of delivering preterm. Cervical change in the following 24 hours does not seem to improve the prediction.