Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm

Background: Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown. Aim: To identify genetic variants associated with forearm BMD and forearm fractures. Methods: BMD at distal radius, measured by dualenergy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a metaanalysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls. Results: We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (

The relationships between golf and health:A scoping review

OBJECTIVE: To assess the relationships between golf and health. DESIGN: Scoping review. DATA SOURCES: Published and unpublished reports of any age or language, identified by searching electronic databases, platforms, reference lists, websites and from consulting experts. REVIEW METHODS: A 3-step search strategy identified relevant published primary and secondary studies as well as grey literature. Identified studies were screened for final inclusion. Data were extracted using a standardised tool, to form (1) a descriptive analysis and (2) a thematic summary. RESULTS AND DISCUSSION: 4944 records were identified with an initial search. 301 studies met criteria for the scoping review. Golf can provide moderate intensity physical activity and is associated with physical health benefits that include improved cardiovascular, respiratory and metabolic profiles, and improved wellness. There is limited evidence related to golf and mental health. The incidence of golfing injury is moderate, with back injuries the most frequent. Accidental head injuries are rare, but can have serious consequences. CONCLUSIONS: Practitioners and policymakers can be encouraged to support more people to play golf, due to associated improved physical health and mental well-being, and a potential contribution to increased life expectancy. Injuries and illnesses associated with golf have been identified, and risk reduction strategies are warranted. Further research priorities include systematic reviews to further explore the cause and effect nature of the relationships described. Research characterising golf's contribution to muscular strengthening, balance and falls prevention as well as further assessing the associations and effects between golf and mental health are also indicated

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO)

BACKGROUND: Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. METHODS AND FINDINGS: We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. CONCLUSIONS: The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. TRIAL REGISTRATION: This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656

Are antifibrinolytic drugs equivalent in reducing blood loss and transfusion in cardiac surgery? A meta-analysis of randomized head-to-head trials

BACKGROUND: Aprotinin has been shown to be effective in reducing peri-operative blood loss and the need for re-operation due to continued bleeding in cardiac surgery. The lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA) are cheaper, but it is not known if they are as effective as aprotinin. METHODS: Studies were identified by searching electronic databases and bibliographies of published articles. Data from head-to-head trials were pooled using a conventional (Cochrane) meta-analytic approach and a Bayesian approach which estimated the posterior probability of TXA and EACA being equivalent to aprotinin; we used as a non-inferiority boundary a 20% increase in the rates of transfusion or re-operation because of bleeding. RESULTS: Peri-operative blood loss was significantly greater with TXA and EACA than with aprotinin: weighted mean differences were 106 mls (95% CI 37 to 227 mls) and 185 mls (95% CI 134 to 235 mls) respectively. The pooled relative risks (RR) of receiving an allogeneic red blood cell (RBC) transfusion with TXA and EACA, compared with aprotinin, were 1.08 (95% CI 0.88 to 1.32) and 1.14 (95% CI 0.84 to 1.55) respectively. The equivalent Bayesian posterior mean relative risks were 1.15 (95% Bayesian Credible Interval [BCI] 0.90 to 1.68) and 1.21 (95% BCI 0.79 to 1.82) respectively. For transfusion, using a 20% non-inferiority boundary, the posterior probabilities of TXA and EACA being non-inferior to aprotinin were 0.82 and 0.76 respectively. For re-operation the Cochrane RR for TXA vs. aprotinin was 0.98 (95% CI 0.51 to 1.88), compared with a posterior mean Bayesian RR of 0.63 (95% BCI 0.16 to 1.46). The posterior probability of TXA being non-inferior to aprotinin was 0.92, but this was sensitive to the inclusion of one small trial. CONCLUSION: The available data are conflicting regarding the equivalence of lysine analogues and aprotinin in reducing peri-operative bleeding, transfusion and the need for re-operation. Decisions are sensitive to the choice of clinical outcome and non-inferiority boundary. The data are an uncertain basis for replacing aprotinin with the cheaper lysine analogues in clinical practice. Progress has been hampered by small trials and failure to study clinically relevant outcomes

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Outcomes using lower vs higher hemoglobin thresholds for red blood cell transfusion

Clinical Question: Is a lower vs higher hemoglobin threshold best for minimizing both red blood cell use and adverse clinical outcomes when used to trigger red blood cell transfusions in anemic patients in critical care and acute care settings? Bottom Line: Compared with higher hemoglobin thresholds, a hemoglobin threshold of 7 or 8 g/dL is associated with fewer red blood cell units transfused without adverse associations with mortality, cardiac morbidity, functional recovery, or length of hospital stay. The optimal hemoglobin/hematocrit criterion for transfusion remains controversial in several clinical settings. New evidence may best guide clinical practice. This updated Cochrane evidence includes 9 additional studies summarizing a total of 19 randomized controlled clinical trials involving more than 6000 patients that compared clinical outcomes between strategies using a higher vs lower hemoglobin/hematocrit threshold for red blood cell transfusion

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion

Background: Most clinical practice guidelines recommend restrictive red cell transfusion practices, with the goal of minimising exposure to allogeneic blood. The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). Objectives: To examine the evidence for the effect of transfusion thresholds on the use of allogeneic and/or autologous red cell transfusion, and the evidence for any effect on clinical outcomes. Search methods: We identified trials by searching: the Cochrane Injuries Group Specialised Register (searched 1 February 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE (Ovid) 1948 to January Week 3 2011, EMBASE (Ovid) 1980 to 2011 (Week 04), ISI Web of Science: Science Citation Index Expanded (1970 to February 2011) and ISI Web of Science: Conference Proceedings Citation Index - Science (1990 to February 2011). We checked reference lists of other published reviews and relevant papers to identify any additional trials. Selection criteria: Controlled trials in which patients were randomised to an intervention group or to a control group. We included trials where intervention groups were assigned on the basis of a clear transfusion ‘trigger’, described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered. Data collection and analysis: We pooled risk ratios of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes across trials using a random-effects model. Two people performed data extraction and assessment of the risk of bias. Main results: We included 19 trials involving a total of 6264 patients and they were similar enough that results could be combined. Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 39% (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.72). This equates to an average absolute risk reduction (ARR) of 34% (95% CI 24% to 45%). The volume of RBCs transfused was reduced on average by 1.19 units (95% CI 0.53 to 1.85 units). However, heterogeneity between trials was statistically significant (P < 0.00001; I2 ≥ 93%) for these outcomes. Restrictive transfusion strategies did not appear to impact the rate of adverse events compared to liberal transfusion strategies (i.e. mortality, cardiac events, myocardial infarction, stroke, pneumonia and thromboembolism). Restrictive transfusion strategies were associated with a statistically significant reduction in hospital mortality (RR 0.77, 95% CI 0.62 to 0.95) but not 30-day mortality (RR 0.85, 95% CI 0.70 to 1.03). The use of restrictive transfusion strategies did not reduce functional recovery, hospital or intensive care length of stay. The majority of patients randomised were included in good-quality trials, but some items of methodological quality were unclear. There are no trials in patients with acute coronary syndrome. Authors’ conclusions: The existing evidence supports the use of restrictive transfusion triggers in most patients, including those with pre-existing cardiovascular disease. As there are no trials, the effects of restrictive transfusion triggers in high-risk groups, such as acute coronary syndrome, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood, the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells