Comparison of intravenous versus perineural dexamethasone as a local anaesthetic adjunct for peripheral nerve blocks in the lower limb: A meta-analysis and systematic review.

As a local anaesthetic adjunct, the systemic absorption of perineural dexamethasone in the lower limb could be restricted because of decreased vascularity when compared with the upper limb. To compare the pharmacodynamic characteristics of intravenous and perineural dexamethasone in the lower limb. Systematic review of randomised controlled trials with meta-analysis. Systematic search of Central, Google Scholar, Ovid Embase and Ovid Medline to 18 July 2023. Randomised controlled trials, which compared the intravenous with perineural administration of dexamethasone as a local anaesthetic adjunct in peripheral nerve blocks for surgery of the lower limb. The most common peripheral nerve blocks were femoral, sciatic and ankle block. The local anaesthetic was long acting in all trials and the dose of dexamethasone was 8 mg in most trials. The primary outcome, the duration of analgesia, was investigated by all nine trials ( n = 546 patients). Overall, compared with intravenous dexamethasone, perineural dexamethasone increased the duration of analgesia from 19.54 to 22.27 h, a mean difference [95% confidence interval (CI) of 2.73 (1.07 to 4.38) h; P = 0.001, I2 = 87]. The quality of evidence was moderate owing to serious inconsistency. However, analysis based on the location of the peripheral nerve block, the type of local anaesthetic or the use of perineural adrenaline showed no difference in duration between intravenous and perineural dexamethasone. No differences were shown for any of the secondary outcomes related to efficacy and side effects. In summary, moderate evidence supports the superiority of perineural dexamethasone over intravenous dexamethasone in prolonging the duration of analgesia. However, this difference is unlikely to be clinically relevant. Consideration of the perineural use of dexamethasone should recognise that this route of administration remains off label

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)

Evaluation of LEACHMN for simulating seasonal changes in plant available nitrogen across a variable landscape

A model that accurately simulates the seasonal variation in nitrogen (N) dynamics may represent an important additional tool in N management. The objectives of this study were to evaluate whether seasonal changes in the amount of N that becomes available to a maize crop in a variable landscape can be simulated with LEACHMN and, in particular, to assess the potential value of LEACHMN in estimating N available at the time of the presidedress soil nitrate test (PSNT). Soil mineral N (SMN) and shoot N were measured biweekly over seven growing seasons in corn (Zea Mays L.) grown under conventional tillage in a variable landscape in Southern Ontario, Canada. The model was calibrated using data from 2002 and 2003 from each of five positions in the landscape and then evaluated using data from the 1997–2001 growing seasons. Although the model under-estimated SMN and over-estimated shoot N, the model was more successful in simulating the sum, defined as plant available N (PAN). Simulations of PAN were best at the summit and shoulder positions. The agreement between measured and simulated PAN were poorest early in the season. Although the accuracy of PAN simulations late in the growing season indicates this model has potential value in N management decisions, the errors in simulating SMN early in the season suggest adjustments are required before it can be used, along with other tools, as a substitute for the PSNT in cool humid environments. Key words: Soil mineral N, Plant available N, variable landscapes, LEACHMN </jats:p

Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty

Little is known about genes regulating male puberty. Further, while many identified pubertal timing 1variants associate with age at menarche, a late manifestation of puberty, and body mass, little is known about these variants' relationship to pubertal initiation or tempo. To address these questions, we performed genome-wide association meta-analysis in over 11 000 European samples with data on early pubertal traits, male genital and female breast development, measured by the Tanner scale. We report the first genome-wide significant locus for male sexual development upstream of myocardin-like 2 (MKL2) (P = 8.9×10-9), amenarche locus tagging a developmental pathway linking earlier puberty with reduced pubertal growth (P = 4.6×10-5) and short adult stature (p = 7.5×10-6) in both males and females. Furthermore, our results indicate that a proportion of menarche loci are important for pubertal initiation in both sexes. Consistent with epidemiological correlations between increased prepubertal body mass and earlier pubertal timing in girls, body mass index (BMI)-increasing alleles correlated with earlier breast development. In boys, some BMI-increasing alleles associated with earlier, and others with delayed, sexual development; these genetic results mimic the controversy in epidemiological studies, some of which show opposing correlations between prepubertal BMI and male puberty. Our results contribute to our understanding of the pubertal initiation program in both sexes and indicate that although mechanisms regulating pubertal onset in males and females may largely be shared, the relationship between body mass and pubertal timing in boys may be complex and requires further genetic studies. © The Author 2014. Published by Oxford University Press. All rights reserved

Common variants at 6q22 and 17q21 are associated with intracranial volume

During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P &amp;lt; 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.&lt;/p&gt

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values &lt;5 × 10-5, Bonferroni-corrected P&lt;0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation