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Background Postpartum haemorrhage (PPH) is a major cause of maternal morbidity and mortality and its incidence is increasing in many countries despite management guidelines. A national quality improvement programme called the Obstetric Bleeding Strategy for Wales (OBS Cymru) was introduced in all obstetric units in Wales. The aim was to reduce moderate PPH (1000 mL) progressing to massive PPH ( >  2500 mL) and the need for red cell transfusion. Methods A PPH care bundle was introduced into all 12 obstetric units in Wales included all women giving birth in 2017 and 2018 ( n  = 61,094). The care bundle prompted: universal risk assessment, quantitative measurement of blood loss after all deliveries (as opposed to visual estimation), structured escalation to senior clinicians and point-of-care viscoelastometric-guided early fibrinogen replacement. Data were submitted by each obstetric unit to a national database. Outcome measures were incidence of massive PPH ( >  2500 mL) and red cell transfusion. Analysis was performed using linear regression of the all Wales monthly data. Results Uptake of the intervention was good: quantitative blood loss measurement and risk assessment increased to 98.1 and 64.5% of all PPH >  1000 mL, whilst ROTEM use for PPH  >  1500 mL increased to 68.2%. Massive PPH decreased by 1.10 (95% CI 0.28 to 1.92) per 1000 maternities per year ( P  = 0.011). Fewer women progressed from moderate to massive PPH in the last 6 months, 74/1490 (5.0%), than in the first 6 months, 97/1386 (7.0%), ( P  = 0.021). Units of red cells transfused decreased by 7.4 (95% CI 1.6 to 13.2) per 1000 maternities per year ( P  = 0.015). Red cells were transfused to 350/15204 (2.3%) and 268/15150 (1.8%) ( P  = 0.001) in the first and last 6 months, respectively. There was no increase in the number of women with lowest haemoglobin below 80 g/L during this time period. Infusions of fresh frozen plasma fell and there was no increase in the number of women with haemostatic impairment. Conclusions The OBS Cymru care bundle was feasible to implement and associated with progressive, clinically significant improvements in outcomes for PPH across Wales. It is applicable across obstetric units of widely varying size, complexity and staff mixes.

The effects of an enzyme-hydrolyzed arabinoxylan from wheat (AXOS) versus an intact arabinoxylan from flax (FLAX) added to a ready-to-eat cereal (RTEC) on the postprandial appetitive, hormonal, and metabolic responses in overweight women (BMI 25.0–29.9 kg/m2) were evaluated. Subsequent meal energy intake was also assessed. Two randomized, double-blind, crossover design studies were completed. For trial 1, the participants consumed the following RTEC breakfast, matched for total weight and varied in energy content: low-fiber (LF, 4 g); high-fiber (HF, 15 g) as either AXOS or FLAX. For trial 2, the participants consumed LF, HF-AXOS, and HF-FLAX RTECs but also consumed another LF breakfast that was isocaloric (LF-iso) to that of the HF breakfasts. Perceived appetite and blood samples (trial 2 only) were assessed before and after breakfast. An ad libitum lunch was offered 4 h post-breakfast. No differences in postprandial appetite responses were observed among any breakfasts in either trial. The HF-AXOS and HF-FLAX led to increased postprandial GLP-1 and peptide YY (PYY) concentrations vs. LF-iso. No differences were observed in lunch meal energy intake among breakfast meals in either trial. Collectively, these data suggest that 15 g of low molecular weight fiber added to RTECs did not affect perceived appetite or subsequent energy intake despite differences in satiety hormone signaling in overweight females.

BackgroundPostpartum haemorrhage (PPH) contributes to substantial maternal morbidity. Research into PPH has led to improvements in care which have been incorporated into the Obstetric Bleeding Strategy for Wales.InterventionA national quality improvement team supported local teams in implementing multiple interventions including risk assessment, objective measurement of blood loss, multiprofessional assessment (at the bedside at 1000 mL blood loss) and point-of-care (POC) testing of coagulation to guide blood product resuscitation during PPH. The project was rolled out to all 12 obstetric units in 2017. The interventions were reinforced by an All Wales Guideline, PPH proforma and standardised training. A national database, biannual audits, and patient and staff surveys reported process and outcome measures.ResultsProcess measures: during 2017, there was an increase in the percentage of maternities with documented risk assessment (0%–76%), objective measurement of blood loss (52%–88%) and POC testing for coagulation for PPH ≥1500 mL (38%–59%). Maternity staff survey indicated that 94% were aware of the project and 87% stated that it had changed their unit’s management of PPH. Interim outcome measures: the incidence (95% CI) of PPH ≥2500 mL per 1000 maternities in 2017 was 6.03 (5.23–6.95). The annual number of women receiving any red blood cell transfusion, level 3 intensive care admission and hysterectomy for PPH was 19.7 (18.2 to 21.3), 0.702 (0.464 to 1.06) and 0.255 (0.129 to 0.504) per 1000 maternities, respectively.ConclusionsA high level of project awareness across Welsh maternity units has been achieved. Measurement of blood loss was reported to be the most important early change in practice, while PPH documentation and POC testing continue to be embedded. Combining qualitative and quantitative measures to inform implementation has improved project delivery and allowed teams to adapt to local contexts.

To assess the effect of food form (FF) on postprandial (PP) plasma amino acid (AA) concentrations, ten older adults (five men and five women, age 72 (sem 2) years, BMI 26·0 (sem 0·9) kg/m2) consumed, on separate days, energy and macronutrient-matched test meal replacement products (MRP) (approximately 25 % of the subject's daily energy need; approximately 54 % carbohydrate, 21 % protein, 25 % fat) in beverage and solid form. Blood samples were taken during fasting and throughout the 4 h PP period; plasma AA concentrations were assessed using HPLC. Consumption of each MRP led to an increase in total AA, branched-chain AA (BCAA), essential AA (EAA), non-essential AA (NEAA) and leucine concentrations (4 h area under the curve, AUC) (time effect; P < 0·05). The beverage MRP resulted in a greater initial (i.e. 30 min) and sustained (4 h AUC) increase in total AA, BCAA, EAA, NEAA and leucine concentrations compared with the solid MRP (each effect of FF; P < 0·05). Although there was no effect of FF on PP insulin response, glucose concentration was greater 1 and 2 h after the solid MRP was consumed (FF × time interaction; P < 0·05). For all PP time points combined, total AA concentration was positively associated with plasma insulin (r 0·25) and glucose (r 0·24) concentrations for the solid MRP but not for the beverage MRP. In conclusion, older adults can achieve higher plasma AA concentrations when a protein-containing MRP is ingested in beverage form. The implications of the higher AA availability on anabolic processes warrant investigation.

Functional capacity is an important component of risk assessment for major surgery. Doctors' clinical subjective assessment of patients' functional capacity has uncertain accuracy. We did a study to compare preoperative subjective assessment with alternative markers of fitness (cardiopulmonary exercise testing [CPET], scores on the Duke Activity Status Index [DASI] questionnaire, and serum N-terminal pro-B-type natriuretic peptide [NT pro-BNP] concentrations) for predicting death or complications after major elective non-cardiac surgery. We did a multicentre, international, prospective cohort study at 25 hospitals: five in Canada, seven in the UK, ten in Australia, and three in New Zealand. We recruited adults aged at least 40 years who were scheduled for major non-cardiac surgery and deemed to have one or more risk factors for cardiac complications (eg, a history of heart failure, stroke, or diabetes) or coronary artery disease. Functional capacity was subjectively assessed in units of metabolic equivalents of tasks by the responsible anaesthesiologists in the preoperative assessment clinic, graded as poor (<4), moderate (4–10), or good (>10). All participants also completed the DASI questionnaire, underwent CPET to measure peak oxygen consumption, and had blood tests for measurement of NT pro-BNP concentrations. After surgery, patients had daily electrocardiograms and blood tests to measure troponin and creatinine concentrations until the third postoperative day or hospital discharge. The primary outcome was death or myocardial infarction within 30 days after surgery, assessed in all participants who underwent both CPET and surgery. Prognostic accuracy was assessed using logistic regression, receiver-operating-characteristic curves, and net risk reclassification. Between March 1, 2013, and March 25, 2016, we included 1401 patients in the study. 28 (2%) of 1401 patients died or had a myocardial infarction within 30 days of surgery. Subjective assessment had 19·2% sensitivity (95% CI 14·2–25) and 94·7% specificity (93·2–95·9) for identifying the inability to attain four metabolic equivalents during CPET. Only DASI scores were associated with predicting the primary outcome (adjusted odds ratio 0·96, 95% CI 0·83–0·99; p=0·03). Subjectively assessed functional capacity should not be used for preoperative risk evaluation. Clinicians could instead consider a measure such as DASI for cardiac risk assessment. Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research, Innovation and Science, UK National Institute of Academic Anaesthesia, UK Clinical Research Collaboration, Australian and New Zealand College of Anaesthetists, and Monash University.

The distribution of body fat, or fat patterning, is an important risk factor for cardiovascular disease and diabetes, independent of obesity. Furthermore, the incidence of cardiovascular disease and diabetes varies by ethnicity. We documented ethnic differences in anthropometrie characteristics and body fat distribution between Anglo, Black, and Mexican American men (n = 101), women (n = 245), boys (n = 111), and girls (n = 111). We used aggregates of skinfold measures to examine ethnic differences in the deposition of fat in body compartments (body, trunk, leg, and arm) and analyzed trunk-extremity skinfold ratios to determine which best reflected ethnic differences in fat distribution. The results show that Mexican American mothers have larger skinfold ratios and more body fat (as determined by skinfold aggregates) than either Anglo or Black American mothers, whereas Black American mothers have larger ratios than Anglo American mothers. Mexican American fathers also have larger skinfold ratios but not more body fat (skinfold aggregates) than Anglo American fathers. Mexican American fathers have more body fat than Black American fathers, but we found no differences between skinfold ratios. The ethnic differences among children in skinfold ratios and aggregates are similar to those found among fathers, with more differences among girls than boys. Fat patterning differences do exist among the three ethnicities, with greater trunk fat among Mexican and Black Americans. Those ethnicities are known to be at higher risk for cardiovascular disease and diabetes.

There is a large decrease in endogenous estrogen production with menopause associated with increases in severity of risk factors for coronary heart disease (CHD), including lower high density lipoprotein cholesterol (HDL-C) concentrations. Exogenous estrogen is administered to decrease the risk of CHD. This project was designed to examine the influence of hormone replacement therapy (HRT), ethnicity, and body composition on cholesterol ester transfer protein (CETP) and lecithin:cholesterol acyltransferase (LCAT) activities, two enzymes involved in HDL metabolism. 205 women participated, 32% of Hispanic origin and 52% not presently undergoing HRT (58% Anglo, 39% Hispanic). CETP and LCAT activities were quantified by a mass transfer method and body composition variables were measured by dual energy x-ray absorptiometry and anthropometry. There were no significant differences in plasma lipids and lipoproteins among HRT groups (non-users, unopposed estrogen, combined therapy). Hispanic women had lower HDL-C concentrations and total plasma cholesterol to HDL-C ratio, and higher triglyceride concentrations and greater susceptibility of low density lipoprotein particles to oxidation. CETP activity was elevated in Hispanic women when compared to Anglo women. The ethnic difference in CETP activity was eliminated once IAAT or measures of trunk fat, but not total body fatness, were controlled. No differences in CETP or LCAT activities were found among HRT groups. Women not undergoing HRT tended to have greater abdominal fat compared to women undergoing either hormone therapy, however differences were not significant. Hispanic women had significantly greater amounts of abdominal fat than did Anglo women, even after adjusting for total body fat. CETP and LCAT activities were positively related to plasma lipids, lipoproteins (exception: negative association with HDL-C), and body composition. Correlations were higher with regional fat measures than with total body fat measures. In conclusion, HRT did not affect CETP or LCAT activities. Results suggest that associations between HRT use and decreased risk of CHD involve other mechanisms. Hispanic women had higher CETP activities and greater distribution of abdominal body fat suggesting that they are at greater risk for CHD compared to Anglo women.

We analyzed results of the Matthews Youth Test for Health for Anglo-American, black, and Mexican-American 5- and 6-year-old children to address three questions: (1) Do these children differ in the prevalence of type A behavior pattern or its component scales? (2) Are blood pressures or heart rates related to ethnicity, gender, or type A behavior pattern? (3) Can possible confounding factors account for observed differences? We identified several differences related to traditional risk factors: (1) Mexican Americans had the lowest systolic blood pressure, (2) girls had higher diastolic blood pressures than boys, and (3) black and Mexican-American boys had lower heart rates. Our analysis also revealed a significant gender-ethnicity interaction. Anglo- and Mexican-American girls had lower impatience-aggression scores than any other group. We detected no interaction effects for competitiveness scores, nor was there any significant relationship between competitiveness and blood pressure. We did find relationships between type A behavior pattern and blood pressure; these relationships were strengthened by use of the impatience-aggression subscale. Use of covariates strengthened observed associations. We conclude that the effects of type A behavior pattern on cardiovascular disease may be mediated by conventional risk factors.

Enabling parents to create a smoke-free home is one of the key ways that children’s exposure to second-hand smoke (SHS) can be reduced. Smoke-free home interventions have largely targeted mothers who smoke, and there is little understanding of the barriers and facilitators that fathers experience in creating a smoke-free home. Systematic searches combining terms for fathers, homes, and SHS exposure were run in April 2019 in Web of Science’s Citation Indices, PsycINFO, and PubMed for English-language studies published since 2008. The searches identified 980 records for screening, plus 66 records from other sources. Twelve studies reported in 13 papers were included in this scoping review. Eight of the studies were conducted in Asian countries (five in China, one in India, one in Japan, and one in Iran), three were conducted in Canada, and one in Turkey. Findings were extracted in verbatim text for thematic analysis. The review identified that attitudes and knowledge, cultural and social norms, gender power relations, and shifting perceptions and responsibilities related to fatherhood can impact on fathers’ views of their role in relation to creating and maintaining a smoke-free home. There were too few published studies that had assessed smoke-free home interventions with fathers to draw conclusions regarding effective approaches. Research is clearly needed to inform our understanding of fathers’ roles, successes and challenges in creating and maintaining a smoke-free home, so that father-inclusive rather than mother-led interventions can be developed to benefit entire households and improve gender equity as well as health.

ObjectiveA GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay.MethodsWe used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS.Results and conclusionsWe show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze–thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.