Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Self-Sustaining Square-Extensional Mode Resonator Oscillator for Mass Sensing in Liquid

We present a 5.41 MHz square-extensional (SE) mode resonator in closed-loop oscillation for resonant mass sensing in the liquid phase. The resonator has been fabricated in piezoelectric thin film aluminum nitride (AlN) on silicon (Si). The strain profile of the SE mode allows for higher electromechanical coupling efficiency using piezoelectric transduction to lower the motional resistance (Rm) given the expected low quality factors (Q) in liquid (136 compared to 942 in air). By locking the device into self-sustained oscillation, the minimum detectable frequency shift is reduced from 3680 ppm (open-loop in water) to 8.76 ppm (closed-loop in air)

Design of an Improved Traditional Baking Oven and evaluation of Baking Performance

Small-scale baking ovens are built by the local workers and usually no scientific principles are followed to design and build of it. Modern scientific principles and procedures are followed to design and fabricate the baking ovens using low-cost materials. The major drawbacks of this type of traditional oven are: improper control of baking temperature; contamination of products with ashes during heating and excess cost for heating. This study aimed at modeling heat and mass transfer during baking, and evaluating the quality characteristics of bread and cake. The problems were identified by conducting a one-time cross-sectional survey, and the heat and mass transfer were modeled by designing and fabricating an improved oven. This model predicted the bread temperature and moisture content at 160, 170, 180, 190 and 200°C oven temperatures. The result indicated that increasing the oven temperature from 160 to 200°C increased the bread crust temperature from 101.58 to 158.69°C. However, the temperature and weight of bread increased gradually with increasing baking time up to 18-20 min and then started declining until it reached equilibrium after 30 min. The weight loss of bread increased with increasing bread temperature. The model predicted fairly accurate bread temperature and weight loss. It predicted 20 to 132°C against the observed 22 to 115°C during baking at 200°C oven temperature, 0 to 40% weight loss against 0 to 49% observed weight loss. The developed improved oven required 25% less time for baking bread and cake compared to the traditional one. Loaves of bread baked in the improved oven had 27.4% lower moisture content, 660 cm3 higher volume, and 408 g lower crumb firmness value compared to the conventional baking process. The improved baking oven is, therefore, more efficient than traditional baking ovens in terms of heat and mass transfer, baking time and product quality. [J Bangladesh Agril Univ 2023; 21(2.000): 203-213

Technique and Circuit for Contactless Readout of Piezoelectric MEMS Resonator Sensors

A technique and electronic circuit for contactless electromagnetic interrogation of piezoelectric micro-electromechanical system (MEMS) resonator sensors are proposed. The adopted resonator is an aluminum-nitride (AlN) thin-film piezoelectric-on-silicon (TPoS) disk vibrating in radial contour mode at about 6.3 MHz. The MEMS resonator is operated in one-port configuration and it is connected to a spiral coil, forming the sensor unit. A proximate electronic interrogation unit is electromagnetically coupled through a readout coil to the sensor unit. The proposed technique exploits interleaved excitation and detection phases of the MEMS resonator. A tailored electronic circuit manages the periodic switching between the excitation phase, where it generates the excitation signal driving the readout coil, and the detection phase, where it senses the transient decaying response of the resonator by measuring through a high-impedance amplifier the voltage induced back across the readout coil. This approach advantageously ensures that the readout frequency of the MEMS resonator is first order independent of the interrogation distance between the readout and sensor coils. The reported experimental results show successful contactless readout of the MEMS resonator independently from the interrogation distance over a range of 12 mm, and the application as a resonant sensor for ambient temperature and as a resonant acoustic-load sensor to detect and track the deposition and evaporation processes of water microdroplets on the MEMS resonator surface

Folic acid, vitamin B12 and homocysteine levels following olanzapine administration in schizophrenia patients

The purpose of this study was to assess the levels of folic acid, vitamin B12 and homocysteine in the serum of schizophrenia patients (n=20) and to evaluate the effect of olanzapine on these biomarkers. The blood was also collected from the 10 healthy volunteers as control. Compared to control, the serum folic acid (p=0.005) and vitamin B12 levels (p=0.211) were higher in the schizophrenia patients, whereas no difference was evident in the serum homocysteine level. But significantly higher levels of serum folic acid (p=0.005), vitamin B12 (p=0.047) and significantly lower level of serum homocysteine (p=0.000) were observed after 10 weeks of olanzapine administration. BPRS score was reduced significantly after intervention. The Pearson correlation coefficient test showed a statistically not significant negative relationship between the serum folate, vitamin B12 and homocysteine levels. In conclusion, olanzapine can significantly elevate the  serum folic acid and vitamin B12 levels whereas it can lower the serum homocysteine level which may contribute to the improvement of symptoms of schizophrenia

Anatomical and karyotypic comparison of induced tetraploid of Oryza sativa var Latisail with the allotetraploid halophytic wild rice Oryza coarctata

The allotetraploid wild rice, Oryza coarctata grows in sea water and is the only halophyte which sets rice-like grains. It is a unique genetic resource for introducing salt tolerance into elite rice cultivars of Oryza sativa. Hybridization between these two remains unsuccessful. Our aim was to induce tetraploidization in the traditional Latisail cultivar of rice and compare its anatomical features to O. coarctata. Colchicine was used on the apical shoot tips of germinating seeds to produce the induced autotetraploid of Oryza sativa. Detailed anatomical comparisons of the leaves, stems, roots and chromosomes of the diploid and induced tetraploid of the Latisail variant of O. sativa and wild O. coarctata were carried out. Chromosomes of the induced tetraploid of O. sativa were shorter than diploid O. sativa, but longer than the 48 chromosomes in O. coarctata. The anatomical features of the induced tetraploid, like the number and size of bundle sheath cells, vascular bundle sizes and cuticle sizes were closer to that of the perennial allotetraploid, O. coarctata. It had more than twice the number of bulliform cells compared to the diploid and the number was similar to those found in O. coarctata. Crosses between the induced tetraploid and O. coarctata produced fertile offspring resembling O. sativa with evidence of small introgressions from O. coarctata pollens. The induced tetraploid of the Latisail variant of O. sativa and its progeny with O. coarctata are valuable plant genetic resources and may help introduce the vigorous halophytic traits of O. coarctata into commercial rice.Bangladesh Climate Change Trust Fund12 month embargo; published: 13 December 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]