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Objective: To use data from routine sources to compare rates of obstetric intervention in Europe both overall and for subgroups at higher risk of intervention.Design: Retrospective analysis of aggregated routine data.Setting: Thirty-one European countries or regions contributing data on mode of delivery to the Euro-Peristat project.Population: Births in participating countries in 2010.Methods: Countries provided aggregated data about overall rates of obstetric intervention and about caesarean section rates for specified subgroups.Main Outcome Measures: Mode of delivery.Results: Rates of caesarean section ranged from 14.8% to 52.2% of all births and rates of instrumental vaginal delivery ranged from 0.5% to 16.4%. Overall, there was no association between rates of instrumental vaginal delivery and rates of caesarean section, but similarities were observed between some countries that are geographically close and may share common traditions of practice. Associations were observed between caesarean section rates for women with breech and vertex births and with singleton and multiple births but patterns of association for women who had and had not had previous caesarean sections were more complex.Conclusions: The persisting wide variations in caesarean section and instrumental vaginal delivery rates point to a lack of consensus about practice and raise questions for further investigation. Further research is needed to explore the impact of differences in clinical guidelines, healthcare systems and their financing and parents' and professionals' attitudes to care at delivery. [ABSTRACT FROM AUTHOR]

Background: Ultrasound (US) guidance, in some instances, can increase the success rate and reduce the onset and procedure times for peripheral nerve blockade compared with traditional nerve localization techniques. The presumptive mechanism for these benefits is the ability to accurately inject local anesthetic circumferentially around the target nerve. We aimed to determine whether ensuring circumferential spread of local anesthetic is advantageous for US-guided popliteal sciatic nerve block.Methods: Sixty-four adult patients undergoing US-guided popliteal sciatic block for elective foot and ankle surgery were randomly assigned to 1 of 2 groups, circumferential or single-location injection. Using a short-axis nerve view and out-of-plane needle approach, the needle tip was advanced to the posterior external surface of the sciatic nerve. A 30-mL local anesthetic admixture (1:1 lidocaine 2%/bupivacaine 0.5% with 1:200,000 epinephrine) was injected either entirely at this location (single location) or incrementally at multiple locations to ensure circumferential spread around the sciatic nerve (circumferential). Sensory and motor functions were assessed by a blinded observer at predetermined intervals. The primary outcome was sensory block defined as loss of sensation to pinprick in the distribution of both tibial and common peroneal nerves at 30 mins after injection.Results: Sensory block was achieved in 94% of patients in the circumferential injection group compared with 69% in the single-location injection group (P = 0.010). There were no differences detected in block performance time, pain during block performance, or block-related complications between groups.Conclusions: Ultrasound-guided circumferential injection of local anesthetic around the sciatic nerve at the popliteal fossa can improve the rate of sensory block without an increase in block procedure time or block-related complications compared with a single-location injection technique. [ABSTRACT FROM AUTHOR]

Recent animal studies have provided insight and understanding, as well as promising clinical tools, to help identify needle-to-nerve contact and potentially hazardous intraneural injection. This narrative review describes and summarizes the contemporary animal studies primarily relating to indicators of needle-to-nerve contact and intraneural injection. Resultant nerve injury, whenever sought, is discussed. [ABSTRACT FROM AUTHOR]

The use of ultrasound to facilitate regional anesthesia is an evolving area of clinical, education, and research interests. As our community's experience grows, it has become evident that anesthesiologists performing "routine" ultrasound-guided blocks may very well be confronted with atypical or even pathologic anatomy. As an educational resource for anesthesiologists, the following articles present examples of common sonopathology that may be encountered during ultrasound-guided regional anesthesia. This present article describes sonopathology related to blood vessels and nerves. [ABSTRACT FROM AUTHOR]

Total knee arthroplasty (TKA) is amenable to various regional anesthesia techniques that may improve patient outcome. We sought to answer whether regional anesthesia decreased mortality, cardiovascular morbidity, deep venous thrombosis and pulmonary embolism, blood loss, duration of surgery, pain, opioid-related adverse effects, cognitive defects, and length of stay. We also questioned whether regional anesthesia improved rehabilitation. To do so, we performed a systematic review of the contemporary literature comparing general anesthesia and/or systemic analgesia with regional anesthesia and/or regional analgesia for TKA. To reflect contemporary surgical and anesthetic practice, only randomized, controlled trials from 1990 onward were included. We identified 28 studies involving 1538 patients. There was insufficient evidence from randomized, controlled trials alone to conclude if anesthetic technique influenced mortality, cardiovascular morbidity other than postoperative hypotension, or the incidence of deep venous thrombosis and pulmonary embolism when using thromboprophylaxis. Our review suggests there was no difference in perioperative blood loss or duration of surgery in patients who received general anesthesia versus regional anesthesia. Compared with general anesthesia and/or systemic analgesia, regional anesthesia and/or analgesia reduced postoperative pain, morphine consumption, and opioid-related adverse effects. Length of stay may be reduced and rehabilitation facilitated for patients undergoing regional anesthesia and analgesia for TKA. [ABSTRACT FROM AUTHOR]

Combined spinal and epidural anaesthesia (CSEA) has previously been shown to result in a higher sensory block than equivalent single shot spinal anaesthesia (SSSA). In nonpregnant patients, hypotension was also more pronounced in the CSEA group. The aim of this randomized trial was to compare the haemodynamic stabilities of CSEA and SSSA during elective caesarean section when the same dose of anaesthetic was administered. This was studied directly by measuring the noninvasive arterial blood pressure (BP) and indirectly by the amount of ephedrine required to maintain baseline BP. Systemic vascular resistance index (SVRI) and cardiac index (CI) were also measured using thoracic impedance cardiography.~Background and Objectives~Objective~Seventy women received hyperbaric bupivacaine (12.5 mg) and diamorphine (0.3 mg) intrathecally via either CSEA or SSSA. Noninvasive arterial BP, CI and SVRI were measured every 2 min. The total ephedrine used was calculated.~Methods~Methods~There were no significant differences between the groups in ephedrine requirements (P = 0.38), intraoperative mean arterial pressure (P = 0.77), CI (P = 0.17) or SVRI (P = 0.10).~Results~Results~CSEA placement appears to offer no haemodynamic benefits compared with SSSA when the same dose of local anaesthetic is administered.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]

The NHS plan announced sustained increases in funding accompanied by wide ranging reform, the success of which would be measured by targets set across the board, including increases in numbers of beds, staff, hospitals and equipment. In this article we assess progress towards the target of 7,000 extra beds in hospitals and intermediate care to be achieved by 2004. Summary points are as follows. (1) Although the 2003/2004 target for availability of general and acute NHS beds in England was achieved, the increase did not offset the overall decrease in all categories of beds. Bed availability fell by 2083, from 1,86,290 in 1999/2000 to 1,84,207 in 2003/2004, following a fall of 12,558 from 1996/1997 to 1999/2000. (2) Lack of standardized definitions and data collection systems both within the NHS and for the independent sector, compounded by ambiguity over the funding of extra capacity for the NHS, call into question the accuracy of data collected about intermediate care beds. (3) Systems for collecting data about intermediate care should be made subject to the same code of practice as official NHS statistics in order to monitor future targets and plan for provision of care. (4) Changes in definitions, lack of detail about criteria used in setting targets and lack of data about private sector care, make it impossible to monitor the overall capacity available to the NHS and assess whether bed availability targets have been met. [ABSTRACT FROM AUTHOR]

The statistical adequacy of all papers published in the period 1976-80 describing clinical trials of five non-steroidal anti-inflammatory and two analgesic drugs introduced into the UK market in 1978 and 1979 has been assessed using a checklist of simple criteria. Most trials were reported to be randomised and double-blind. Trial designs were less satisfactory in other important respects; the sample size of most trials was inadequate to demonstrate superiority of the new drug compared with an active control therapy. The period of treatment assessment was short in view of the likelihood of prolonged prescription of drugs in these classes. It is suggested that licensing authorities should demand higher standards of clinical trial evidence offered in support of new drugs. [ABSTRACT FROM AUTHOR]

Importance: The White House National Strategy on Hunger, Nutrition, and Health included expanding free school meals to all students, regardless of income, which has sparked debate in the United States., Objective: To assess the association between universal free school meals (UFSMs) and school and student outcomes in the United States., Evidence Review: An expert panel-informed protocol was developed to evaluate intervention or cohort studies comparing UFSM programs, such as the Community Eligibility Provision (CEP), with non-UFSM programs in US schools from August 2012 (excluding 2020-2021 due to the COVID-19 pandemic) in peer-reviewed publications or government reports. Outcomes included meal participation rates, attendance, dietary intake and quality, food waste, economic impact, food insecurity, anthropometrics, disciplinary actions, stigma, and shaming. A search of Medline, Econlit, Business Source Ultimate, ERIC, Agricola, Cab Abstracts, and CINAHL was performed in April 2024. Two researchers screened articles for inclusion, extracted data, and assessed risk of bias, using the Risk of Bias in Nonrandomized Studies of Interventions tool, for each included study. Grading of Recommendations, Assessment, Development, and Evaluations was used to assess the certainty of evidence for each outcome., Findings: The search identified 2784 records, with 6 studies included, representing more than 11 000 elementary, middle, and high schools. Nonrandomized intervention studies performed difference-in-difference or rate ratio analysis to investigate CEP participation rates, attendance, anthropometrics, and/or suspensions. CEP was associated with increased lunch (3 studies; moderate certainty) and breakfast (1 study; very low certainty) participation. School attendance was unchanged or improved in schools with CEP compared with schools without UFSM (2 studies; low certainty). CEP was associated with lower obesity prevalence (1 study; very low certainty) and fewer suspensions (1 study; very low certainty). Reasons for downgrading the certainty ratings included indirectness (data not fully representative of the United States) and inconsistency (small number of studies limiting ability to assess consistency). Despite the limitations, the evidence reflected well-designed longitudinal intervention studies appropriate for decision-making., Conclusions and Relevance: In this systematic review, UFSMs were associated with increased meal participation, no or slight improvements in attendance, and decreased obesity prevalence and suspension rates; certainty of evidence was moderate for lunch participation and low or very low for other outcomes. Studies did not report several important outcomes, such as diet quality and food security, suggesting the need for more high-quality research encompassing policy-relevant indicators.

Objectives: Different tools to assess the potential risk of bias (RoB) for cross-sectional studies have been developed, but it is unclear whether all pertinent bias concepts are addressed. We aimed to identify RoB concepts applicable to cross-sectional research validity and to explore coverage for each in existing appraisal tools., Study Design and Setting: This scoping review followed the Joanna Briggs Institute methodology. We included records of any study design describing or reporting methods, concepts or tools used to consider RoB in health research reported to be descriptive/prevalence survey or analytic/association (cross-sectional) study designs. Synthesis included quantitative and qualitative analysis., Results: Of the 4556 records screened, 90 were selected for inclusion; 67 (74%) described the development of, or validation process for, appraisal tools, 15 (17%) described methodological content or theory relevant to RoB for cross-sectional studies and 8 (9%) records of methodological systematic reviews. Review of methodological reports identified important RoB concepts for both descriptive/prevalence and analytic/association studies. Tools identified (n = 64 unique tools) were either intended to appraise quality or assess RoB in multiple study designs including cross-sectional studies (n = 21; 33%) or cross-sectional designs alone (n = 43; 67%). Several existing tools were modified (n = 17; 27%) for application to cross-sectional studies. The RoB items most frequently addressed in the RoB tools were validity and reliability of the exposure (53%) or outcome (65%) measurement and representativeness of the study population (59%). Most tools did not consider nonresponse or missingness appropriately or at all., Conclusion: Assessing cross-sectional studies involve unique RoB considerations. We identified RoB tools designed for broad applicability across various study designs as well as those specifically tailored for cross-sectional studies. However, none of the identified tools comprehensively address all potential biases pertinent to cross-sectional studies. Our findings indicate a need for continued improvement of RoB tools and suggest that the development of context-specific or more precise tools for this study design may be necessary., Competing Interests: Declaration of competing interest There are no competing interests for any author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Gestational exposure to toxic environmental chemicals and maternal social hardships are individually associated with impaired fetal growth, but it is unclear whether the effects of environmental chemical exposure on infant birth weight are modified by maternal hardships., Methods: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a pan-Canadian cohort of 1982 pregnant females enrolled between 2008 and 2011. We quantified eleven environmental chemical concentrations from two chemical classes - six organochlorine compounds (OCs) and five metals - that were detected in ≥ 70% of blood samples collected during the first trimester. We examined fetal growth using birth weight adjusted for gestational age and assessed nine maternal hardships by questionnaire. Each maternal hardship variable was dichotomized to indicate whether the females experienced the hardship. In our analysis, we used elastic net to select the environmental chemicals, maternal hardships, and 2-way interactions between maternal hardships and environmental chemicals that were most predictive of birth weight. Next, we obtained effect estimates using multiple linear regression, and plotted the relationships by hardship status for visual interpretation., Results: Elastic net selected trans-nonachlor, lead, low educational status, racially minoritized background, and low supplemental folic acid intake. All were inversely associated with birth weight. Elastic net also selected interaction terms. Among those with increasing environmental chemical exposures and reported hardships, we observed stronger negative associations and a few positive associations. For example, every two-fold increase in lead concentrations was more strongly associated with reduced infant birth weight among participants with low educational status (β = -100 g (g); 95% confidence interval (CI): -215, 16), than those with higher educational status (β = -34 g; 95% CI: -63, -3). In contrast, every two-fold increase in mercury concentrations was associated with slightly higher birth weight among participants with low educational status (β = 23 g; 95% CI: -25, 71) compared to those with higher educational status (β = -9 g; 95% CI: -24, 6)., Conclusions: Our findings suggest that maternal hardships can modify the associations of gestational exposure to some OCs and metals with infant birth weight., (© 2024. The Author(s).)

Background: Anterior cruciate ligament (ACL) injuries are among the most common injuries in adolescent athletes and result in significant financial and physical morbidity. Evidence-based programs designed to prevent ACL injury are effective. However, their adoption remains low. We sought to evaluate the awareness, evidence-based implementation, and barriers to implementation of ACL injury prevention programs (ACL-IPP) among youth athletic coaches., Hypothesis: Higher education level of the coach, higher level of training, number of teams coached, and coaching female teams would be associated with ACL-IPP implementation., Study Design: Cross-sectional survey., Level of Evidence: Level 4., Methods: We conducted an email survey sent to all 63 school districts within Section VI of the New York State Public High School Athletic Association. We employed descriptive statistics and tests of correlation to identify factors associated with ACL-IPP implementation., Results: A total of 73% of coaches said they were aware of ACL-IPP, and only 12% of coaches implemented ACL-IPP according to best evidence. Coaches of higher competitive levels were more likely to adopt ACL-IPP ( P = 0.01), more likely to use them multiple times per week ( P = 0.03), and for ≥1 seasons ( P = 0.02). Coaches of multiple teams were more likely to adopt ACL-IPP ( P = 0.01). There were no differences in evidence-based implementation of ACL-IPP with gender coached or level of education of the coach., Conclusion: Overall awareness, adoption, and evidence-based implementation of ACL-IPP remain low. These results suggest that coaches at higher levels of play and multiple teams tend to use ACL-IPP more often. Gender coached and level of education do not appear to be associated with awareness or implementation., Clinical Relevance: Evidence-based ACL-IPP implementation remains low. Targeting coaches of younger athletes and fewer teams with local outreach programs and ACL-IPP may increase the implementation of ACL-IPP., Competing Interests: The following author declared potential conflicts of interest: L.J.B. has received a grant from NIH.

Background & Aims: Ultra-processed food (UPF) intake has increased sharply over the last few decades and has been consistently asserted to be implicated in the development of non-communicable diseases. We aimed to evaluate and update the existing observational evidence for associations between ultra-processed food (UPF) consumption and human health., Methods: We searched Medline and Embase from inception to March 2023 to identify and update meta-analyses of observational studies examining the associations between UPF consumption, as defined by the NOVA classification, and a wide spectrum of health outcomes. For each health outcome, we estimated the summary effect size, 95% confidence interval (CI), between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate evidence credibility of the identified associations., Results: This umbrella review identified 39 meta-analyses on the associations between UPF consumption and health outcomes. We updated all meta-analyses by including 122 individual articles on 49 unique health outcomes. The majority of the included studies divided UPF consumption into quartiles, with the lowest quartile being the reference group. We identified 25 health outcomes associated with UPF consumption. For observational studies, 2 health outcomes, including renal function decline (OR: 1.25; 95% CI: 1.18, 1.33) and wheezing in children and adolescents (OR: 1.42; 95% CI: 1.34, 1.49), showed convincing evidence (Class I); and five outcomes were reported with highly suggestive evidence (Class II), including diabetes mellitus, overweight, obesity, depression, and common mental disorders., Conclusions: High UPF consumption is associated with an increased risk of a variety of chronic diseases and mental health disorders. At present, not a single study reported an association between UPF intake and a beneficial health outcome. These findings suggest that dietary patterns with low consumption of UPFs may render broad public health benefits., Competing Interests: Conflicts of interest The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The partially hydrogenated oil (PHO) prohibition came into effect in Canada in September 2018 to reduce the intakes of total trans fatty acids (t-TFAs) and industrially produced TFAs (i-TFAs)., Objectives: We aimed to estimate the red blood cell (RBC) proportions of t-TFA (primary objective) and total 18:1 TFA (secondary objective) of adults in Canada before the PHO prohibition and to identify the population subgroups at risk of higher TFA intakes., Methods: We pooled data from 4025 adult participants of the cross-sectional Canadian Health Measures Survey cycles 3 and 4 (2012-2015). We estimated mean proportions, relative to total fatty acids (FAs), of RBC t-TFA and 18:1 TFA and their associations with sociodemographic, health, and lifestyle characteristics using multiple linear regression models., Results: The nonadjusted mean RBC proportions of t-TFA and total 18:1 TFA were 0.59% (95% CI: 0.54, 0.63) and 0.27% (95% CI: 0.25, 0.29), respectively. In the adjusted models, the same participant characteristics were associated with t-TFA and 18:1 TFA but differences were generally smaller for 18:1 TFA than for t-TFA. Race, BMI, and alcohol intake were independently associated with RBC t-TFA and 18:1 TFA. Asian and Black participants had lower RBC t-TFA (-0.05% and -0.10% of total FA, respectively) than White participants. Obesity and high risk alcohol drinking were associated with slightly lower (≤0.06%) t-TFA proportions than lower adiposity and alcohol intake concentrations, respectively., Conclusions: Pre-PHO prohibition in food in Canada, t-TFA proportions were relatively low compared with a proposed threshold of 1% of total RBC FAs, over which cardiovascular disease risk may be higher. Previous voluntary initiatives to reduce i-TFA in the food supply may explain these relatively low RBC t-TFA concentrations. Some population subgroups had higher baseline RBC TFA than other subgroups, but the physiological implications of these small differences, at relatively low baseline RBC TFA proportions, remain to be determined., Competing Interests: Conflict of interest Amanda Macfarlane is an Associate Editor for The American Journal of Clinical Nutrition and played no role in the Journal’s evaluation of the manuscript. The rest of the authors declare no conflict of interest related to this study., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Cross-sectional studies are commonly used to study human health and disease, but are especially susceptible to bias. This scoping review aims to identify and describe available tools to assess the risk of bias (RoB) in cross-sectional studies and to compile the key bias concepts relevant to cross-sectional studies into an item bank. Using the JBI scoping review methodology, the strategy to locate relevant RoB concepts and tools is a combination of database searches, prospective review of PROSPERO registry records; and consultation with knowledge users and content experts. English language records will be included if they describe tools, checklists, or instruments which describe or permit assessment of RoB for cross-sectional studies. Systematic reviews will be included if they consider eligible RoB tools or use RoB tools for RoB of cross-sectional studies. All records will be independently screened, selected, and extracted by one researcher and checked by a second. An analytic framework will be used to structure the extraction of data. Results for the scoping review are pending. Results from this scoping review will be used to inform future selection of RoB tools and to consider whether development of a new RoB tool for cross-sectional studies is needed., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V.)

Background: Prolonged opioid use is associated with higher complications and worse patient-reported outcomes following total shoulder arthroplasty (TSA). Identified risk factors for prolonged postoperative use are related to several medical comorbidities, gender, diagnoses of anxiety or depressive disorders, and preoperative opioid use. In this study, we hypothesized that patient-reported mental health characteristics can help to identify patients at risk of worse postoperative pain control, worse sleep, and higher opioid utilization following TSA., Methods: Ninety-three consecutive patients were asked to fill out 2 mental health questionnaires prior to undergoing TSA. Following surgery, patients filled out a daily pain diary to track their daily pain, pain medication use, and quality and duration of their sleep for 30 days. Preoperative opioid use and postoperative refill were determined by the New York State Prescription Monitoring Program. Mixed-model linear regressions were conducted. Significance was defined as p  < 0.05., Results: Postoperative opioid refill was associated with female gender, preoperative opioid therapy, higher inpatient opioid use, worse anxiety, depression, somatization, and pain catastrophizing scores. The number of days using opioids postoperatively was associated with worse pain catastrophizing scale (PCS) and somatization scores (patient health questionnaire-15). Preoperative opioid therapy was associated with worse somatization scores, whereas no opioids used after surgery were associated with better somatization scores. Worse sleep quality and duration were associated with worse PCS scores., Conclusion: A greater mental health burden is associated with worse postoperative pain control and higher opioid utilization during the acute postoperative period. This is especially evident in the pain catastrophizing and somatization domains., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The organochlorine dichlorodiphenyltrichloroethane (DDT) is banned worldwide owing to its negative health effects. It is exceptionally used as an insecticide for malaria control. Exposure occurs in regions where DDT is applied, as well as in the Arctic, where its endocrine disrupting metabolite, p , p ' - dichlorodiphenyldichloroethylene ( p , p ' - DDE) accumulates in marine mammals and fish. DDT and p , p ' - DDE exposures are linked to birth defects, infertility, cancer, and neurodevelopmental delays. Of particular concern is the potential of DDT use to impact the health of generations to come via the heritable sperm epigenome., Objectives: The objective of this study was to assess the sperm epigenome in relation to p , p ' - DDE serum levels between geographically diverse populations., Methods: In the Limpopo Province of South Africa, we recruited 247 VhaVenda South African men and selected 50 paired blood serum and semen samples, and 47 Greenlandic Inuit blood and semen paired samples were selected from a total of 193 samples from the biobank of the INUENDO cohort, an EU Fifth Framework Programme Research and Development project. Sample selection was based on obtaining a range of p , p ' -DDE serum levels ( mean = 870.734 ± 134.030  ng / mL ). We assessed the sperm epigenome in relation to serum p , p ' -DDE levels using MethylC-Capture-sequencing (MCC-seq) and chromatin immunoprecipitation followed by sequencing (ChIP-seq). We identified genomic regions with altered DNA methylation (DNAme) and differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3) in sperm., Results: Differences in DNAme and H3K4me3 enrichment were identified at transposable elements and regulatory regions involved in fertility, disease, development, and neurofunction. A subset of regions with sperm DNAme and H3K4me3 that differed between exposure groups was predicted to persist in the preimplantation embryo and to be associated with embryonic gene expression., Discussion: These findings suggest that DDT and p , p ' - DDE exposure impacts the sperm epigenome in a dose-response-like manner and may negatively impact the health of future generations through epigenetic mechanisms. Confounding factors, such as other environmental exposures, genetic diversity, and selection bias, cannot be ruled out. https://doi.org/10.1289/EHP12013.

Assisted reproductive technologies (ART) account for 1-6% of births in developed countries. While most children conceived are healthy, increases in birth and genomic imprinting defects have been reported; such abnormal outcomes have been attributed to underlying parental infertility and/or the ART used. Here, we assessed whether paternal genetic and lifestyle factors, that are associated with male infertility and affect the sperm epigenome, can influence ART outcomes. We examined how paternal factors, haploinsufficiency for Dnmt3L, an important co-factor for DNA methylation reactions, and/or diet-induced obesity, in combination with ART (superovulation, in vitro fertilization, embryo culture and embryo transfer), could adversely influence embryo development and DNA methylation patterning in mice. While male mice fed high-fat diets (HFD) gained weight and showed perturbed metabolic health, their sperm DNA methylation was minimally affected by the diet. In contrast, Dnmt3L haploinsufficiency induced a marked loss of DNA methylation in sperm; notably, regions affected were associated with neurodevelopmental pathways and enriched in young retrotransposons, sequences that can have functional consequences in the next generation. Following ART, placental imprinted gene methylation and growth parameters were impacted by one or both paternal factors. For embryos conceived by natural conception, abnormality rates were similar for WT and Dnmt3L+/- fathers. In contrast, paternal Dnmt3L+/- genotype, as compared to WT fathers, resulted in a 3-fold increase in the incidence of morphological abnormalities in embryos generated by ART. Together, the results indicate that embryonic morphological and epigenetic defects associated with ART may be exacerbated in offspring conceived by fathers with sperm epimutations., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Introduction Needle tip visualisation is a key skill required for the safe practice of ultrasound-guided regional anaesthesia (UGRA). This exploratory study assesses the utility of a novel augmented reality device, NeedleTrainer™, to differentiate between anaesthetists with varying levels of UGRA experience in a simulated environment. Methods Four groups of five participants were recruited (n = 20): novice, early career, experienced anaesthetists, and UGRA experts. Each participant performed three simulated UGRA blocks using NeedleTrainer™ on healthy volunteers (n = 60). The primary aim was to determine whether there was a difference in needle tip visibility, as calculated by the device, between groups of anaesthetists with differing levels of UGRA experience. Secondary aims included the assessment of simulated block conduct by an expert assessor and subjective participant self-assessment. Results The percentage of time the simulated needle tip was maintained in view was higher in the UGRA expert group (57.1%) versus the other three groups (novice 41.8%, early career 44.5%, and experienced anaesthetists 43.6%), but did not reach statistical significance (p = 0.05). An expert assessor was able to differentiate between participants of different UGRA experience when assessing needle tip visibility (novice 3.3 out of 10, early career 5.1, experienced anaesthetists 5.9, UGRA expert group 8.7; p < 0.01) and final needle tip placement (novice 4.2 out of 10, early career 5.6, experienced anaesthetists 6.8, UGRA expert group 8.9; p < 0.01). Subjective self-assessment by participants did not differentiate UGRA experience when assessing needle tip visibility (p = 0.07) or final needle tip placement (p = 0.07). Discussion An expert assessor was able to differentiate between participants with different levels of UGRA experience in this simulated environment. Objective NeedleTrainer™ and subjective participant assessments did not reach statistical significance. The findings are novel as simulated needling using live human subjects has not been assessed before, and no previous studies have attempted to objectively quantify needle tip visibility during simulated UGRA techniques. Future research should include larger sample sizes to further assess the potential use of such technology., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2023, Shevlin et al.)

Background: Folate and vitamin B12 status during pregnancy are important for maternal and neonatal health. Maternal intake and prepregnancy body mass index (ppBMI) can influence biomarker status., Objectives: This study aimed to, throughout pregnancy; 1) assess folate and B12 status including serum total folate, plasma total vitamin B12, and homocysteine (tHcy); 2) examine how these biomarkers are associated with intakes of folate and B12 and with ppBMI; and 3) determine predictors of serum total folate and plasma total vitamin B12., Methods: In each trimester (T1, T2, and T3), food and supplement intakes of 79 French-Canadian pregnant individuals were assessed by 3 dietary recalls (R24W) and a supplement use questionnaire. Fasting blood samples were collected. Serum total folate and plasma total vitamin B12 and tHcy were assessed by immunoassay (Siemens ADVIA Centaur XP)., Results: Participants were 32.1 ± 3.7 y and had a mean ppBMI of 25.7 ± 5.8 kg/m 2 . Serum total folate concentrations were high (>45.3 nmol/L, T1: 75.4 ± 55.1, T2: 69.1 ± 44.8, T3: 72.1 ± 52.1, P = 0.48). Mean plasma total vitamin B12 concentrations were >220 pmol/L (T1: 428 ± 175, T2: 321 ± 116, T3: 336 ± 128, P < 0.0001). Mean tHcy concentrations were <11 μmol/L across trimesters. Most participants (79.6%-86.1%) had a total folic acid intake above the Tolerable Upper Intake Level (UL, >1000 μg/d). Supplement use accounted for 71.9%-76.1% and 35.3%-41.8% of total folic acid and vitamin B12 intakes, respectively. The ppBMI was not correlated with serum total folate (P > 0.1) but was weakly correlated with and predicted lower plasma total vitamin B12 in T3 (r = -0.23, P = 0.04; r 2 = 0.08, standardized beta [sβ] = -0.24, P = 0.01). Higher folic acid intakes from supplements predicted higher serum total folate (T1: r 2 = 0.05, sβ = 0.15, P = 0.04, T2: r 2 = 0.28, sβ = 0.56, P = 0.01, T3: r 2 = 0.19, sβ = 0.44, P < 0.0001)., Conclusions: Most pregnant individuals had elevated serum total folate concentrations, reflecting total folic acid intakes above the UL driven by supplement use. Vitamin B12 concentrations were generally adequate and differed by ppBMI and pregnancy stage., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Fetal alcohol exposure at any stage of pregnancy can lead to fetal alcohol spectrum disorder (FASD), a group of life-long conditions characterized by congenital malformations, as well as cognitive, behavioral, and emotional impairments. The teratogenic effects of alcohol have long been publicized; yet fetal alcohol exposure is one of the most common preventable causes of birth defects. Currently, alcohol abstinence during pregnancy is the best and only way to prevent FASD. However, alcohol consumption remains astoundingly prevalent among pregnant women; therefore, additional measures need to be made available to help protect the developing embryo before irreparable damage is done. Maternal nutritional interventions using methyl donors have been investigated as potential preventative measures to mitigate the adverse effects of fetal alcohol exposure. Here, we show that a single acute preimplantation (E2.5; 8-cell stage) fetal alcohol exposure (2 × 2.5 g/kg ethanol with a 2h interval) in mice leads to long-term FASD-like morphological phenotypes (e.g. growth restriction, brain malformations, skeletal delays) in late-gestation embryos (E18.5) and demonstrate that supplementing the maternal diet with a combination of four methyl donor nutrients, folic acid, choline, betaine, and vitamin B12, prior to conception and throughout gestation effectively reduces the incidence and severity of alcohol-induced morphological defects without altering DNA methylation status of imprinting control regions and regulation of associated imprinted genes. This study clearly supports that preimplantation embryos are vulnerable to the teratogenic effects of alcohol, emphasizes the dangers of maternal alcohol consumption during early gestation, and provides a potential proactive maternal nutritional intervention to minimize FASD progression, reinforcing the importance of adequate preconception and prenatal nutrition., (© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Although a number of health outcomes such as CVDs, metabolic-related outcomes, neurological disorders, pregnancy outcomes, and cancers have been identified in relation to B vitamins, evidence is of uneven quality and volume, and there is uncertainty about putative causal relationships., Objectives: To explore the effects of B vitamins and homocysteine on a wide range of health outcomes based on a large biorepository linking biological samples and electronic medical records., Methods: First, we performed a phenome-wide association study (PheWAS) to investigate the associations of genetically predicted plasma concentrations (genetic component of the circulating concentrations) of folate, vitamin B6, vitamin B12, and their metabolite homocysteine with a wide range of disease outcomes (including both prevalent and incident events) among 385,917 individuals in the UK Biobank. Second, 2-sample Mendelian randomization (MR) analysis was used to replicate any observed associations and detect causality. We considered MR P <0.05 as significant for replication. Third, dose-response, mediation, and bioinformatics analyses were carried out to examine any nonlinear trends and to disentangle the underlying mediating biological mechanisms for the identified associations., Results: In total, 1117 phenotypes were tested in each PheWAS analysis. After multiple corrections, 32 phenotypic associations of B vitamins and homocysteine were identified. Two-sample MR analysis supported that 3 of them were causal, including associations of higher plasma vitamin B6 with lower risk of calculus of kidney (OR: 0.64; 95% CI: 0.42, 0.97; P = 0.033), higher homocysteine concentration with higher risk of hypercholesterolemia (OR: 1.28, 95% CI: 1.04, 1.56; P = 0.018), and chronic kidney disease (OR: 1.32, 95% CI: 1.06, 1.63; P = 0.012). Significant nonlinear dose-response relationships were observed for the associations of folate with anemia, vitamin B12 with vitamin B-complex deficiencies, anemia and cholelithiasis, and homocysteine with cerebrovascular disease., Conclusions: This study provides strong evidence for the associations of B vitamins and homocysteine with endocrine/metabolic and genitourinary disorders., (Copyright © 2023 American Society for Nutrition. All rights reserved.)

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler's Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother-child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; -2.01 [-3.43, -0.59], p = 0.006), verbal composite (-1.93 [-3.33, -0.53], p = 0.007), and information scale (-0.41 [-0.70, -0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%-41% and 7%-22%, respectively, and accounted for approximately 5%-10% greater variation in male children's cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.

Transparent reporting of nutrition research promotes rigor, reproducibility, and relevance to human nutrition. We performed a scoping review of recent articles reporting dietary folate interventions in mice as a case study to determine the reporting frequency of generic study design items (i.e., sex, strain, and age) and nutrition-specific items (i.e., base diet composition, intervention doses, duration, and exposure verification) in basic nutrition research. We identified 798 original research articles in the EMBASE, Medline, Food Science and Technology Abstracts (FSTA), Global Health, and International Pharmaceutical Abstracts (IPA) databases published between January 2009 and July 2021 in which a dietary folic acid (FA) intervention was used in mice. We identified 312 original peer-reviewed articles including 191 studies in nonpregnant and 126 in pregnant mice. Most studies reported sex (99%), strain (99%), and age (83%). The majority of studies used C57BL/6 (53%) or BALB/c (11%) mice aged 3-9 wk. Nonpregnancy studies were more likely to use only male mice (57%). Dietary FA interventions varied considerably and overlapped: deficiency (0-3 mg/kg), control (0-16 mg/kg), and supplemented (0-50 mg/kg). Only 63% of studies used an open-formula base diet with a declared FA content and 60% of studies verified FA exposure using folate status biomarkers. The duration of intervention ranged from 1 to 104 wk for nonpregnancy studies. The duration of intervention for pregnancy studies was 1-19 wk, occurring variably before pregnancy and/or during pregnancy and/or lactation. Overall, 17% of studies did not report ≥1 generic study design item(s) and 40% did not report ≥1 nutrition-specific study design item(s). The variability and frequent lack of reporting of important generic and nutrition-specific study design details in nutrition studies limit their generalizability, reproducibility, and interpretation. The use of reporting checklists for animal research would enhance reporting quality of key study design and conduct factors in animal-based nutrition research., (© Her Majesty the Queen in Right of Canada, as represented by the Minister of Health, 2022.)

National health and nutrition monitoring is an important federal effort in the United States and Canada, and the basis for many of their nutrition and health policies. Understanding of child exposures through human milk (HM) remains out of reach due to lack of current and representative data on HM's composition and intake volume. This article provides an overview of the current national health and nutrition monitoring activities for HM-fed children, HM composition (HMC) and volume data used for exposure assessment, categories of potential measures in HM, and associated variability factors. In this Perspective, we advocate for a framework for collection and reporting of HMC data for national health and nutrition monitoring and programmatic needs, including a shared vision for a publicly available Human Milk Composition Data Repository (HMCD-R) to include essential metadata associated with HMC. HMCD-R can provide a central, integrated platform for researchers and public health officials for compiling, evaluating, and sharing HMC data. The compiled compositional and metadata in HMCD-R would provide pertinent measures of central tendency and variability and allow use of modeling techniques to approximate compositional profiles for subgroups, providing more accurate exposure assessments for purposes of monitoring and surveillance. HMC and related metadata could facilitate understanding the complexity and variability of HM composition, provide crucial data for assessment of infant and maternal nutritional needs, and inform public health policies, food and nutrition programs, and clinical practice guidelines., (Published by Oxford University Press on behalf of the American Society for Nutrition 2022.)

Background: Achieving optimal folate status during early gestation reduces the risk of neural tube defects (NTDs). While inadequate folate intake remains a concern, it is becoming increasingly common for individuals to consume higher than recommended doses of folic acid (FA) with minimal additional benefit., Objective: Here, we sought to investigate the determinants, including FA supplement dose and use, of plasma total and individual folate vitamer concentrations in the first and third trimesters of pregnancy., Methods: Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a cohort exposed to mandatory FA fortification, we measured plasma total folate and individual folate vitamer [5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), and non-methyl folates (sum of THF, 5-formylTHF, 5,10-methenyl-THF)] concentrations in the first and third trimesters (n = 1,893). Using linear mixed models, we estimated associations between plasma folate concentrations, total daily supplemental FA intake, plasma vitamin B-12 concentrations, and multiple demographic, maternal, and reproductive factors., Results: Almost 95% of MIREC study participants met or exceeded the recommended daily supplemental FA intake from supplements (≥400 μg/d), with approximately 25% consuming more than the Tolerable Upper Intake Level (>1000 μg/d). Over 99% of MIREC participants had a plasma total folate status indicative of maximal NTD risk reduction (25.5 nmol/L) regardless of FA supplement dose. UMFA was detected in almost all participants, with higher concentrations associated with higher FA doses. Determinants of adequate FA supplement intake and folate status associated with reduced NTD risk included indicators of higher socioeconomic position, higher maternal age, nulliparity, and lower prepregnancy BMI., Conclusions: In the context of mandatory FA fortification, our data indicate that higher-than-recommended FA doses are unwarranted, with the exception of individuals at higher risk for NTDs. Ideally, prenatal supplements would contain 400 rather than 1000 µg FA, thereby enabling the consumption of optimal and safe FA doses., (© Crown copyright 2022.)

Persistent organic pollutants (POPs) are ubiquitous in the environment, which is of concern since they are broadly toxic for wildlife and human health. It is generally accepted that maternal prenatal folic acid supplementation (FA) may beneficially impact offspring development, but it has been recently shown that the father's exposures also influence the health of his offspring. Bone is an endocrine organ essential for whole-body homeostasis and is susceptible to toxicants. Herein, we tested the hypotheses that prenatal paternal exposure to POPs induces developmental bone disorders in fetuses across multiple generations and that FA supplementation attenuates these disorders. We used a four-generation rat model, in which F0 founder females were divided into four treatment groups. F0 females were gavaged with corn oil or an environmentally-relevant POPs mixture and fed either a control diet (2 mg FA/kg), or FA supplemented diet (6 mg FA/kg) before mating and until parturition (four treatments in total). After the birth of the F1 litters, all F0 females and subsequent generations received the FA control diet. Staining with alcian blue and alizarin red S of male and female fetal skeletons was performed at Gestational Day 19.5. Paternal direct and ancestral exposure to POPs delayed bone ossification and decreased the length of long limb bones in fetuses. Maternal FA supplementation did not counteract the POPs-associated delayed fetal ossification and reduced long bone length. In conclusion, prenatal paternal POPs exposure causes developmental bone abnormalities over multiple generations, which were not corrected by maternal FA supplementation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MW declared a shared affiliation, with no collaboration, with one of the authors, AM, to the handling editor at the time of the review., (Copyright © 2022 L. Charest, Tessougue, Lessard, Herst, Navarro, Kimmins, Trasler, MacFarlane, Benoit-Biancamano, Bailey and Dalvai.)

Gestational arsenic exposure adversely impacts child health. Folate-mediated 1-carbon metabolism facilitates urinary excretion of arsenic and may prevent arsenic-related adverse health outcomes. We investigated the potential for maternal folate status to modify associations between gestational arsenic exposure and child health. We used data from 364 mother-child pairs in the MIREC study, a prospective pan-Canadian cohort. During pregnancy, we measured first trimester urinary arsenic concentrations, plasma folate biomarkers, and folic acid supplementation intake. At age 3 years, we evaluated twelve neurodevelopmental and anthropometric features. Using latent profile analysis and multinomial regression, we developed phenotypic profiles of child health, estimated covariate-adjusted associations between arsenic and these phenotypic profiles, and evaluated whether folate status modified these associations. We identified three phenotypic profiles of neurodevelopment and three of anthropometry, ranging from less to more optimal child health. Gestational arsenic was associated with decreased odds of optimal neurodevelopment. Maternal folate status did not modify associations of arsenic with neurodevelopmental phenotypic profiles, but gestational arsenic was associated with increased odds of excess adiposity among those who exceed recommendations for folic acid (>1000 μg/day). However, arsenic exposure was low and folate status was high. Gestational arsenic exposure may adversely impact child neurodevelopment and anthropometry, and maternal folate status may not modify these associations; however, future work should examine these associations in more arsenic-exposed or lower folate-status populations.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following: RWP has received personal fees for consultancies unrelated to this topic from Amgen, Biogen, Merck, Nant Pharma, Pfizer, and Reckitt Benckiser. All other authors have no conflicts to disclose.

Background: Dietary exposure assessments are a critical issue in evaluating human nutrition studies; however, nutrition-specific criteria are not consistently included in existing bias assessment tools., Objectives: Our objective was to develop a set of risk of bias (RoB) tools that integrated nutrition-specific criteria into validated generic assessment tools to address RoB issues, including those specific to dietary exposure assessment., Methods: The Nutrition QUality Evaluation Strengthening Tools (NUQUEST) development and validation process included 8 steps. The first steps identified 1) a development strategy; 2) generic assessment tools with demonstrated validity; and 3) nutrition-specific appraisal issues. This was followed by 4) generation of nutrition-specific items and 5) development of guidance to aid users of NUQUEST. The final steps used established ratings of selected studies and feedback from independent raters to 6) assess reliability and validity; 7) assess formatting and usability; and 8) finalize NUQUEST., Results: NUQUEST is based on the Scottish Intercollegiate Guidelines Network checklists for randomized controlled trials, cohort studies, and case-control studies. Using a purposive sample of 45 studies representing the 3 study designs, interrater reliability was high (Cohen's κ: 0.73; 95% CI: 0.52, 0.93) across all tools and at least moderate for individual tools (range: 0.57-1.00). The use of a worksheet improved usability and consistency of overall interrater agreement across all study designs (40% without worksheet, 80%-100% with worksheet). When compared to published ratings, NUQUEST ratings for evaluated studies demonstrated high concurrent validity (93% perfect or near-perfect agreement). Where there was disagreement, the nutrition-specific component was a contributing factor in discerning exposure methodological issues., Conclusions: NUQUEST integrates nutrition-specific criteria with generic criteria from assessment tools with demonstrated reliability and validity. NUQUEST represents a consistent and transparent approach for evaluating RoB issues related to dietary exposure assessment commonly encountered in human nutrition studies., (© Her Majesty the Queen in Right of Canada, as represented by the Minister of Health, 2021.)

Folate and choline are interconnected metabolically. The MTHFD1 R653Q SNP is a risk factor for birth defects and there are concerns that choline deficiency may interact with this SNP and exacerbate health risks. 80-90% of women do not meet the Adequate Intake (AI) for choline. The objective of this study was to assess the effects of choline deficiency on maternal one-carbon metabolism and reproductive outcomes in the MTHFD1-synthetase deficient mouse ( Mthfd1S ), a model for MTHFD1 R653Q. Mthfd1S +/+ and Mthfd1S +/- females were fed control (CD) or choline-deficient diets (ChDD; 1/3 the amount of choline) before mating and during pregnancy. Embryos were evaluated for delays and defects at 10.5 days gestation. Choline metabolites were measured in the maternal liver, and total folate measured in maternal plasma and liver. ChDD significantly decreased choline, betaine, phosphocholine, and dimethylglycine in maternal liver ( p < 0.05, ANOVA), and altered phosphatidylcholine metabolism. Maternal and embryonic genotype, and diet-genotype interactions had significant effects on defect incidence. Mild choline deficiency and Mthfd1S +/- genotype alter maternal one-carbon metabolism and increase incidence of developmental defects. Further study is required to determine if low choline intakes contribute to developmental defects in humans, particularly in 653QQ women.

Introduction: Arteriovenous fistulae (AVF) are the 'gold standard' vascular access for haemodialysis. Universal usage is limited, however, by a high early failure rate. Several small, single-centre studies have demonstrated better early patency rates for AVF created under regional anaesthesia (RA) compared with local anaesthesia (LA). The mechanistic hypothesis is that the sympathetic blockade associated with RA causes vasodilatation and increased blood flow through the new AVF. Despite this, considerable variation in practice exists in the UK. A high-quality, adequately powered, multicentre randomised controlled trial (RCT) is required to definitively inform practice., Methods and Analysis: The Anaesthesia Choice for Creation of Arteriovenous Fistula (ACCess) study is a multicentre, observer-blinded RCT comparing primary radiocephalic/brachiocephalic AVF created under regional versus LA. The primary outcome is primary unassisted AVF patency at 1 year. Access-specific (eg, stenosis/thrombosis), patient-specific (including health-related quality of life) and safety secondary outcomes will be evaluated. Health economic analysis will also be undertaken., Ethics and Dissemination: The ACCess study has been approved by the West of Scotland Research and ethics committee number 3 (20/WS/0178). Results will be published in open-access peer-reviewed journals within 12 months of completion of the trial. We will also present our findings at key national and international renal and anaesthetic meetings, and support dissemination of trial outcomes via renal patient groups., Trial Registration Number: ISRCTN14153938., Sponsor: NHS Greater Glasgow and Clyde GN19RE456, Protocol V.1.3 (8 May 2021), REC/IRAS ID: 290482., Competing Interests: Competing interests: AJRM is currently president of Regional Anaesthesia UK (RA-UK). RA-UK has reviewed and endorsed the trial protocol, but has not been involved in the design or development in any way. AJRM has received consulting fees from Heron therapeutics and Intelligent US. RH has received honoraria from GE., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Two questions regarding the scientific literature have become grist for public discussion: 1) what place should P values have in reporting the results of studies? 2) How should the perceived difficulty in replicating the results reported in published studies be addressed? We consider these questions to be 2 sides of the same coin; failing to address them can lead to an incomplete or incorrect message being sent to the reader. If P values (which are derived from the estimate of the effect size and a measure of the precision of the estimate of the effect) are used improperly, for example reporting only significant findings, or reporting P values without account for multiple comparisons, or failing to indicate the number of tests performed, the scientific record can be biased. Moreover, if there is a lack of transparency in the conduct of a study and reporting of study results, it will not be possible to repeat a study in a manner that allows inferences from the original study to be reproduced or to design and conduct a different experiment whose aim is to confirm the original study's findings. The goal of this article is to discuss how P values can be used in a manner that is consistent with the scientific method, and to increase transparency and reproducibility in the conduct and analysis of nutrition research., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

Background and Objectives: While there are several published recommendations and guidelines for trainees undertaking subspecialty Fellowships in regional anesthesia, a similar document describing a core regional anesthesia curriculum for non-fellowship trainees is less well defined. We aimed to produce an international consensus for the training and teaching of regional anesthesia that is applicable for the majority of worldwide anesthesiologists., Methods: This anonymous, electronic Delphi study was conducted over two rounds and distributed to current and immediate past (within 5 years) directors of regional anesthesia training worldwide. The steering committee formulated an initial list of items covering nerve block techniques, learning objectives and skills assessment and volume of practice, relevant to a non-fellowship regional anesthesia curriculum. Participants scored these items in order of importance using a 10-point Likert scale, with free-text feedback. Strong consensus items were defined as highest importance (score ≥8) by ≥70% of all participants., Results: 469 participants/586 invitations (80.0% response) scored in round 1, and 402/469 participants (85.7% response) scored in round 2. Participants represented 66 countries. Strong consensus was reached for 8 core peripheral and neuraxial blocks and 17 items describing learning objectives and skills assessment. Volume of practice for peripheral blocks was uniformly 16-20 blocks per anatomical region, while ≥50 neuraxial blocks were considered minimum., Conclusions: This international consensus study provides specific information for designing a non-fellowship regional anesthesia curriculum. Implementation of a standardized curriculum has benefits for patient care through improving quality of training and quality of nerve blocks., Competing Interests: Competing interests: Alan Macfarlane: received consultancy fees from Intelligent Ultrasound. Amit Pawa: received honoraria from GE Healthcare, Sintetica UK, Pacira and Butterfly Net Inc. Have also consulted for B Braun Medical Ltd. All other authors declare no conflicts or competing interests., (© American Society of Regional Anesthesia & Pain Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Children born preterm (<37 completed weeks' gestation) have a higher risk of infection-related morbidity than those born at term. However, few large, population-based studies have investigated the risk of infection in childhood across the full spectrum of gestational age. The objectives of this study were to explore the association between gestational age at birth and infection-related hospital admissions up to the age of 10 years, how infection-related hospital admission rates change throughout childhood, and whether being born small for gestational age (SGA) modifies this relationship., Methods and Findings: Using a population-based, record-linkage cohort study design, birth registrations, birth notifications and hospital admissions were linked using a deterministic algorithm. The study population included all live, singleton births occurring in NHS hospitals in England from January 2005 to December 2006 (n = 1,018,136). The primary outcome was all infection-related inpatient hospital admissions from birth to 10 years of age, death or study end (March 2015). The secondary outcome was the type of infection-related hospital admission, grouped into broad categories. Generalised estimating equations were used to estimate adjusted rate ratios (aRRs) with 95% confidence intervals (CIs) for each gestational age category (<28, 28-29, 30-31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41 and 42 weeks) and the models were repeated by age at admission (<1, 1-2, 3-4, 5-6, and 7-10 years). An interaction term was included in the model to test whether SGA status modified the relationship between gestational age and infection-related hospital admissions. Gestational age was strongly associated with rates of infection-related hospital admissions throughout childhood. Whilst the relationship attenuated over time, at 7-10 years of age those born before 40 weeks gestation were still significantly higher in comparison to those born at 40 weeks. Children born <28 weeks had an aRR of 6.53 (5.91-7.22) during infancy, declining to 3.16 (2.50-3.99) at ages 7-10 years, in comparison to those born at 40 weeks; whilst in children born at 38 weeks, the aRRs were 1·24 (1.21-1.27) and 1·18 (1.13-1.23), during infancy and aged 7-10 years, respectively. SGA status modified the effect of gestational age (interaction P<0.0001), with the highest rate among the children born at <28 weeks and SGA. Finally, study findings indicated that the associations with gestational age varied by subgroup of infection. Whilst upper respiratory tract infections were the most common type of infection experienced by children in this cohort, lower respiratory tract infections (LRTIs) (<28 weeks, aRR = 10.61(9.55-11.79)) and invasive bacterial infections (<28 weeks, aRR = 6.02 (4.56-7.95)) were the most strongly associated with gestational age at birth. Of LRTIs experienced, bronchiolitis (<28 weeks, aRR = 11.86 (10.20-13.80)), and pneumonia (<28 weeks, aRR = 9.49 (7.95-11.32)) were the most common causes., Conclusions: Gestational age at birth was strongly associated with rates of infection-related hospital admissions during childhood and even children born a few weeks early remained at higher risk at 7-10 years of age. There was variation between clinical subgroups in the strength of relationships with gestational age. Effective infection prevention strategies should include focus on reducing the number and severity of LRTIs during early childhood., Competing Interests: The authors have declared that no competing interests exist.

Background: Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects; however, the extent to which recommendations are met through dietary sources and supplements is not clear., Objectives: Our objective was to evaluate the dietary and supplemental intakes of FA in a Canadian pregnancy cohort and to determine the proportions of pregnant women exceeding the Estimated Average Requirement (EAR) and Tolerable Upper Intake Level (UL)., Methods: FACT (the Folic Acid Clinical Trial) was an international multicenter, randomized, double-blinded, placebo-controlled, phase III trial investigating FA for the prevention of pre-eclampsia in high-risk pregnancies. Participants were enrolled from Canadian sites at 8-16 weeks of gestation. Dietary and supplemental FA intake data were collected through participant interviews and FFQs at the time of FACT enrollment. Categorical data were summarized as n (%) and continuous data as median (IQR)., Results: This study included 1198 participants. Participants consumed 485 μg dietary folate equivalents (DFE)/d (IQR: 370-630 μg DFE/d) from dietary sources of folate and FA. Through diet alone, 43.4% of participants consumed ≥520 μg DFE/d, the EAR for pregnant individuals. Of the 91.9% of participants who consumed daily FA supplements, 0.4% consumed <400 μg FA/d and 96.0% consumed ≥1000 μg/d, the UL for FA. Median (IQR) total folate intake was 2167 μg DFE/d (2032-2325 μg DFE/d); 95.3% of participants met or exceeded the EAR from all sources, but 1069 (89.2%) participants exceeded the UL., Conclusions: The majority of participants in this Canadian pregnancy cohort did not consume the recommended amount of folate from dietary sources. However, most prenatal supplements contained 1000 μg FA, resulting in the majority of women exceeding the UL. With no additional benefit associated with FA intakes beyond the UL for most women, modification of prenatal supplement formulations may be warranted to ensure women meet but do not exceed recommended FA intakes.FACT was registered at clinicaltrials.gov as NCT01355159 and at isrctn.com as ISRCTN23781770., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Periconceptional folic acid (FA) supplementation is recommended to prevent the occurrence of neural tube defects. Currently, most over-the-counter FA supplements in Canada and the United States contain 1 mg FA and some women are prescribed 5 mg FA/d. High-dose FA is hypothesized to impair 1-carbon metabolism. We aimed to determine folate and 1-carbon metabolism biomarkers in pregnant women exposed to 1 mg or 5 mg FA., Objectives: This was an ancillary study within the Folic Acid Clinical Trial (FACT), a randomized, double-blinded, placebo-controlled, phase III trial designed to assess the efficacy of high-dose FA to prevent preeclampsia., Methods: For FACT, women were randomized at 8-16 gestational weeks to receive daily 4.0 mg FA (high dose) or placebo (low dose) plus their usual supplementation (≤1.1 mg). Women were recruited from 3 Canadian FACT centers and provided nonfasting blood samples at 24-26 gestational weeks for measurement of RBC and serum total folate, serum unmetabolized FA (UMFA), tetrahydrofolate (THF), 5-methylTHF, 5-formylTHF, 5,10-methenylTHF, and MeFox (pyrazino-s-triazine derivative of 4α-hydroxy-5-methylTHF, a 5-methylTHF oxidation product); total vitamins B-12 and B-6; and plasma total homocysteine. Group differences were determined using χ2, Fisher exact, and Wilcoxon rank-sum tests., Results: Nineteen (38%) women received high-dose FA and 31 (62%) received low-dose FA. The median RBC folate concentration was 2701 (IQR: 2243-3032) nmol/L and did not differ between groups. The high-dose group had higher serum total folate (median: 148.4 nmol/L, IQR: 110.4-181.2; P = 0.007), UMFA (median: 4.6 nmol/L, IQR: 2.5-33.8; P = 0.008), and 5-methylTHF (median: 126.6 nmol/L, IQR: 98.8-158.6; P = 0.03) compared with the low-dose group (median: 122.8 nmol/L, IQR: 99.5-136.0; median: 1.9 nmol/L, IQR: 0.9-4.1; median: 108.6 nmol/L, IQR: 96.4-123.2, respectively). Other biomarkers of 1-carbon metabolism did not differ., Conclusions: High-dose FA supplementation in early pregnancy increases maternal serum folate but not RBC folate concentrations, suggesting tissue saturation. Higher UMFA concentrations in women receiving high-dose FA supplements suggest that these doses are supraphysiologic but with no evidence of altered 1-carbon metabolism., (© Crown copyright 2021.)