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468 result(s) for "Fraser, William D"
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Hyperparathyroidism
Hyperparathyroidism is due to increased activity of the parathyroid glands, either from an intrinsic abnormal change altering excretion of parathyroid hormone (primary or tertiary hyperparathyroidism) or from an extrinsic abnormal change affecting calcium homoeostasis stimulating production of parathyroid hormone (secondary hyperparathyroidism). Primary hyperparathyroidism is the third most common endocrine disorder, with the highest incidence in postmenopausal women. Asymptomatic disease is common, and severe disease with renal stones and metabolic bone disease arises less frequently now than it did 20–30 years ago. Primary hyperparathyroidism can be cured by surgical removal of an adenoma, increasingly by minimally invasive parathyroidectomy. Medical management of mild disease is possible with bisphosphonates, hormone replacement therapy, and calcimimetics. Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. However, the biochemical definition of vitamin D deficiency and its treatment are subject to much debate. Secondary hyperparathyroidism as the result of chronic kidney disease is important in the genesis of renal bone disease, and several new treatments could help achieve the guidelines set out by the kidney disease outcomes quality initiative.
Risk of Congenital Heart Defects after Ambient Heat Exposure Early in Pregnancy
Congenital heart defects may be environmentally related, but the association with elevated ambient temperature has received little attention. We studied the relationship between outdoor heat during the first trimester of pregnancy and risk of congenital heart defects. We carried out a retrospective cohort study of 704,209 fetuses between 2 and 8 weeks postconception from April to September in Quebec, Canada, 1988-2012. We calculated the prevalence of congenital heart defects at birth according to the number of days women were exposed to maximum temperature ≥ 30°C. In log-binomial regression models, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the relationship of temperature with seven critical and eight noncritical heart defects, adjusted for pregnancy characteristics. Prevalence of congenital heart defects was 979.5 per 100,000 for 10 days or more of temperature ≥ 30°C compared with 878.9 per 100,000 for 0 days of exposure. Temperature was more precisely associated with noncritical than critical defects, which had lower prevalence. Fetuses exposed to 15 days of temperature ≥ 30°C between 2 and 8 weeks postconception had 1.06 times the risk of critical defects (95% CI: 0.67, 1.67) and 1.12 times the risk of noncritical defects (95% CI: 0.98, 1.29) relative to 0 days. Associations were higher for atrial septal defects (PR 1.37, 95% CI: 1.10, 1.70) than for other noncritical defects. For atrial septal defects, associations with elevated temperatures began the 3rd week postconception. Extreme heat exposure during the first trimester may be associated with noncritical heart defects, especially of the atrial septum. Citation: Auger N, Fraser WD, Sauve R, Bilodeau-Bertrand M, Kosatsky T. 2017. Risk of congenital heart defects after ambient heat exposure early in pregnancy. Environ Health Perspect 125:8-14; http://dx.doi.org/10.1289/EHP171.
Performance of SARS-CoV-2 serology tests: Are they good enough?
In the emergency of the SARS-CoV-2 pandemic, great efforts were made to quickly provide serology testing to the medical community however, these methods have been introduced into clinical practice without the complete validation usually required by the regulatory organizations. SARS-CoV-2 patient samples (n = 43) were analyzed alongside pre-pandemic control specimen (n = 50), confirmed respiratory infections (n = 50), inflammatory polyarthritis (n = 22) and positive for thyroid stimulating immunoglobulin (n = 30). Imprecision, diagnostic sensitivity and specificity and concordance were evaluated on IgG serologic assays from EuroImmun, Epitope Diagnostics (EDI), Abbott Diagnostics and DiaSorin and a rapid IgG/IgM test from Healgen. EDI and EuroImmun imprecision was 0.02–14.0% CV. Abbott and DiaSorin imprecision (CV) ranged from 5.2%–8.1% and 8.2%–9.6% respectively. Diagnostic sensitivity of the assays was 100% (CI: 80–100%) for Abbott, EDI and EuroImmun and 95% (CI: 73–100%) for DiaSorin at ≥14 days post PCR. Only the Abbott assay had a diagnostic specificity of 100% (CI: 91–100%). EuroImmun cross-reacted in 3 non-SARS-CoV-2 respiratory infections and 2 controls. The DiaSorin displayed more false negative results and cross-reacted in six cases across all conditions tested. EDI had one cross-reactive sample. The Healgen rapid test showed excellent sensitivity and specificity. Overall, concordance of the assays ranged from 76.1% to 97.9%. Serological tests for SARS-CoV-2 showed good analytical performance. The head-to-head analysis of samples revealed differences in results that may be linked to the use of nucleocapsid or spike proteins. The point of care device tested demonstrated adequate performance for antibody detection.
Common genetic determinants of vitamin D insufficiency: a genome-wide association study
Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1·9×10 −109 for rs2282679, in GC); 11q12 (p=2·1×10 −27 for rs12785878, near DHCR7); and 11p15 (p=3·3×10 −20 for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6·0×10 −10 for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2·47, 95% CI 2·20–2·78, p=2·3×10 −48) or lower than 50 nmol/L (1·92, 1·70–2·16, p=1·0×10 −26) compared with those in the lowest quartile. Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. Full funding sources listed at end of paper (see Acknowledgments).
Concentrations of persistent organic pollutants in maternal and cord blood from the maternal-infant research on environmental chemicals (MIREC) cohort study
Background Pregnant women are an especially important population to monitor for environmental exposures given the vulnerability of the developing fetus. During pregnancy and lactation chemical body burdens may change due to the significant physiological changes that occur. Developmental exposures to some persistent organic pollutants (POPs) have been linked with adverse health outcomes. Methods First trimester maternal and cord blood plasma concentrations of several POPs including polychlorinated biphenyls (PCBs), organochlorine pesticides (OCs), polybrominated diphenyl ethers (PBDE)s and perfluoroalkyl substances (PFASs) were measured in samples from 1983 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) cohort. Predictors of exposure were also identified. Results In maternal plasma, there was >90 % detection for the perfluoroalkyl substances (PFASs) perfluorooctanoic acid (PFOA), perfluoroctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and dichlorodiphenyldichloroethylene (DDE), oxychlordane and PCB 138 and 153. Cord blood plasma had much lower detection rates with low or very limited detection for most PCBs and PBDEs. The PFASs were the most frequently detected (23–64 %) chemical class in cord plasma. In a subset of 1st and 3rd trimester paired samples, PFAS concentrations were found to be strongly correlated and had ICCs ranging from 0.64 (PFOA) to 0.83 (PFHxS). The cord:maternal plasma concentration ratios ranged from 0.14 (PFOS) to 0.87 (oxychlordane, lipid adjusted). Similar to other studies, we found parity, maternal age, income, education, smoking status, pre-pregnancy BMI and fish consumption to be significant predictors for most chemicals. Those participants who were foreign-born had significantly higher concentrations of organochlorinated pesticides and PCBs. Conclusions In the MIREC study, multiple chemical contaminants were quantified in the plasma of pregnant women. In cord plasma PFOA had the highest detection rate. However, compared to other Canadian and international population studies, the MIREC participants had lower contaminant concentrations of these substances.
Quality of care, risk management, and technology in obstetrics to reduce hospital-based maternal mortality in Senegal and Mali (QUARITE): a cluster-randomised trial
Maternal mortality is higher in west Africa than in most industrialised countries, so the development and validation of effective interventions is essential. We did a trial to assess the effect of a multifaceted intervention to promote maternity death reviews and onsite training in emergency obstetric care in referral hospitals with high maternal mortality rates in Senegal and Mali. We did a pragmatic cluster-randomised controlled trial, with hospitals as the units of randomisation and patients as the unit of analysis. 46 public first-level and second-level referral hospitals with more than 800 deliveries a year were enrolled, stratified by country and hospital type, and randomly assigned to either the intervention group (n=23) or the control group with no external intervention (n=23). All women who delivered in each of the participating facilities during the baseline and post-intervention periods were included. The intervention, implemented over a period of 2 years at the hospital level, consisted of an initial interactive workshop and quarterly educational clinically-oriented and evidence-based outreach visits focused on maternal death reviews and best practices implementation. The primary outcome was reduction of risk of hospital-based mortality. Analysis was by intention-to-treat and relied on the generalised estimating equations extension of the logistic regression model to account for clustering of women within hospitals. This study is registered with ClinicalTrials.gov, number ISRCTN46950658. 191 167 patients who delivered in the participating hospitals were analysed (95 931 in the intervention groups and 95 236 in the control groups). Overall, mortality reduction in intervention hospitals was significantly higher than in control hospitals (odds ratio [OR] 0·85, 95% CI 0·73–0·98, p=0·0299), but this effect was limited to capital and district hospitals, which mainly acted as first-level referral hospitals in this trial. There was no effect in second-level referral (regional) hospitals outside the capitals (OR 1·02, 95% CI 0·79–1·31, p=0·89). No hospitals were lost to follow-up. Concrete actions were implemented comprehensively to improve quality of care in intervention hospitals. Regular visits by a trained external facilitator and onsite training can provide health-care professionals with the knowledge and confidence to make quality improvement suggestions during audit sessions. Maternal death reviews, combined with best practices implementation, are effective in reducing hospital-based mortality in first-level referral hospitals. Further studies are needed to determine whether the benefits of the intervention are generalisable to second-level referral hospitals. Canadian Institutes of Health Research.
A Cluster-Randomized Trial to Reduce Cesarean Delivery Rates in Quebec
This multicenter, cluster-randomized trial showed that an intervention involving audits of indications for cesarean delivery, feedback, and implementation of best practices resulted in a significant but small reduction in the cesarean delivery rate as compared with usual care. Rates of cesarean delivery are high in developed countries. 1 – 3 In Canada, these rates increased from 21.2% to 28.0% between 2000 and 2008 and remained stable until 2011. 4 – 6 High rates of cesarean delivery are of substantial concern owing to the potential harm to the mother and her baby associated with a medically unnecessary cesarean delivery and to the related costs of health care. 7 – 15 Providing evidence-based guidance to health professionals regarding the appropriate selection of women who could benefit from cesarean delivery is now a priority. Systematic reviews of strategies designed to reduce cesarean delivery rates and to improve . . .
Exposure to Free and Conjugated Forms of Bisphenol A and Triclosan among Pregnant Women in the MIREC Cohort
Bisphenol A (BPA) and triclosan (TCS) are two nonpersistent chemicals that have been frequently measured in spot urine samples from the general population but less so in pregnant women; however, data are limited on the free (bioactive) and conjugated forms of these phenols. The Maternal-Infant Research on Environmental Chemicals (MIREC) Study addressed these data gaps by utilizing stored maternal urine samples from a large multicenter cohort study of Canadian pregnant women. Concentrations of free and conjugated forms of BPA and TCS were measured in about 1,890 first-trimester urine samples by ultra performance liquid chromatography-tandem mass spectrometry using isotope dilution. The glucuronides of BPA and TCS were the predominant forms of these chemicals measured (detected in 95% and 99% of samples, respectively), whereas the free forms were detected in 43% and 80% of samples, respectively. The geometric mean urinary concentrations for glucuronides of BPA and TCS were 0.80 μg/L (95% CI: 0.75, 0.85) and 12.30 μg/L (95% CI: 11.08, 13.65), respectively. Significant predictors of BPA included maternal age < 25 vs. ≥ 35 years, current smoking, low vs. high household income, and low vs. high education. For TCS, urinary concentrations were significantly higher in women ≥ 25 years of age, never vs. current smokers, and women with high household income and high education. The results from this study represent the largest national-level data on urinary concentrations of free and conjugated forms of BPA and TCS in pregnant women and suggest that maternal characteristics predicting elevated urinary concentrations of these phenols largely act in opposite directions.
The effects of collagen peptides on muscle damage, inflammation and bone turnover following exercise: a randomized, controlled trial
This study examined whether consuming collagen peptides (CP) before and after strenuous exercise alters markers of muscle damage, inflammation and bone turnover. Using a double-blind, independent group’s design, 24 recreationally active males consumed either 20 g day−1 of CP or a placebo control (CON) for 7 days before and 2 days after performing 150 drop jumps. Maximal isometric voluntary contractions, countermovement jumps (CMJ), muscle soreness (200 mm visual analogue scale), pressure pain threshold, Brief Assessment of Mood Adapted (BAM +) and a range of blood markers associated with muscle damage, inflammation and bone turnover C-terminal telopeptide of type 1 collagen (β-CTX) and N-terminal propeptides of type 1 pro-collagen (P1NP) were measured before supplementation (baseline; BL), pre, post, 1.5, 24 and 48 h post-exercise. Muscle soreness was not significantly different in CP and CON (P = 0.071) but a large effect size was evident at 48 h post-exercise, indicative of lower soreness in the CP group (90.42 ± 45.33 mm vs. CON 125.67 ± 36.50 mm; ES = 2.64). CMJ height recovered quicker with CP than CON at 48 h (P = 0.050; CP 89.96 ± 12.85 vs. CON 78.67 ± 14.41% of baseline values; ES = 0.55). There were no statistically significant effects for the other dependent variables (P > 0.05). β-CTX and P1NP were unaffected by CP supplementation (P > 0.05). In conclusion, CP had moderate benefits for the recovery of CMJ and muscle soreness but had no influence on inflammation and bone collagen synthesis.
Effects of resistance exercise, collagen ingestion and circulating oestrogen concentration on collagen synthesis in a female athlete: A case report
We investigated the effects of resistance exercise (RE), hydrolysed collagen (HC) ingestion and circulating oestrogen concentration on collagen synthesis in a naturally menstruating female CrossFit athlete. In a double‐blind, randomised cross‐over design, the participant (36 years; height 1.61 m; mass 82.6 kg) consumed 0 or 30 g HC prior to performing back‐squat RE when endogenous circulating oestrogen concentration was low (onset of menses, OM) and high (late follicular phase, LF) during two consecutive menstrual cycles. Ten 5‐mL blood samples were collected during each of the four interventions to analyse concentrations of serum 17β‐oestradiol, and biomarkers of type I collagen turnover, that is serum procollagen type I N‐terminal propeptide (PINP, a biomarker of collagen synthesis) and plasma β‐isomerised C‐terminal telopeptide of type I collagen (β‐CTX, a biomarker of collagen breakdown), as well as the serum concentration of 18 collagen amino acids. 17β‐Oestradiol concentration was 5‐fold higher at LF (891 ± 116 pmol L−1) than OM (180 ± 13 pmol L−1). The PINP concentration × time area under the curve (AUC) was higher in the 30 g HC OM intervention (201 μg L−1 h) than the 30 g HC LF (144 μg L−1 h), 0 g HC OM (151 μg L−1 h) and 0 g HC LF (122 μg L−1 h) interventions. β‐CTX concentration decreased 1.4‐fold from pre‐RE to 6 h post‐RE in all interventions. Thus, high circulating oestrogen concentration was associated with lower collagen synthesis following RE in this female athlete. Ingesting 30 g HC, however, augmented the collagen synthesis response at LF and particularly at OM. What is the central question of this study? Does resistance exercise‐induced collagen synthesis vary according to circulating oestrogen concentration in a naturally menstruating female athlete, and if so, does hydrolysed collagen ingestion have any impact? What is the main finding and its importance? Exercise‐induced collagen synthesis was low when circulating oestrogen concentration was high and vice versa. However, ingesting 30 g hydrolysed collagen prior to exercise reduced the negative effect of oestrogen on collagen synthesis. As high circulating oestrogen has been associated with greater injury risk in females, supplementing exercise with hydrolysed collagen may help protect these tissues from injury.