METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025.
RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority).
CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).
METHODS: RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score).
RESULTS: Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies).
CONCLUSION: High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients.
PROSPERO REGISTRATION: CRD42022302278.
METHODOLOGY: A prospective hospital-wide point prevalence survey was carried out by a multidisciplinary team in April 2019 at the University Malaya Medical Centre (UMMC) and the Hospital Canselor Tuanku Muhriz (HCTM), Kuala Lumpur, Malaysia. Data was collected from the patient's electronic medical records and recorded using the Hospital National Antimicrobial Prescribing Survey toolkit developed by the National Centre for Antimicrobial Stewardship, Australia.
RESULTS: The appropriateness of prescriptions was 60.1% (UMMC) and 67% (HCTM), with no significant difference between the two hospitals. Compliance with guidelines was 60.0% (UMMC) and 61.5% (HCTM). Amoxicillin-clavulanic acid was the most commonly prescribed antimicrobial (UMMC = 16.9%; HCTM = 11.9%).
CONCLUSIONS: The appropriateness of antimicrobial prescribing in medical wards, compliance with guidelines, and prescribing patterns were similar between the two hospitals in Malaysia. The survey identified several areas of prescribing that would need targeted AMS interventions.
MATERIALS AND METHODS: This is a nationwide, online-based cross-sectional study utilising a self-administered questionnaire that was distributed to tertiary hospital HCWs in Malaysia, conducted between June and August 2020.
RESULTS: Forty-eight physicians, 66 nurses and 79 medical assistants participated in this study. 73.6% correctly recognised PPE components while 40.4% revealed correct hand hygiene practices and approximately 20% had misconceptions about the proper usage of PPE. Although 78.8% disclosed high compliance, 37.3% perceived that PPE protocol interferes with patient care. HCWs have suboptimal knowledge levels of hand hygiene. Age and poor behaviour were the independent predictors of good compliance with PPE.
CONCLUSION: This study highlights the necessity to analyse discrepancies in PPE practice among HCWs and its contributing elements. Recognised barriers should be addressed to narrow the gap between knowledge, attitude and behaviour to improve compliance. The study findings would assist in developing an improved disease transmission control and prevention training protocols for HCWs as a preparation for possible infectious outbreaks in the future.
AIMS: This systematic review aims to determine the factors associated with mosquito control among construction workers.
METHODS: Primarily, articles related to factors associated with mosquito control among construction workers were collected from two different online databases (ScienceDirect and EBSCOhost). Two independent reviewers were assigned to screen the titles and abstracts of the collected data, stored in Microsoft Excel, against the inclusion and exclusion criteria. Afterwards, the quality of the included articles was critically assessed using the Mixed Method Appraisal Tool (MMAT). Of the 171 articles identified, 4 were included in the final review.
RESULTS: Based on the thorough evaluation, mosquito-related knowledge, practical mosquito prevention measures, and Larval Source Management (LSM) were identified as vital factors associated with mosquito control among construction workers. The significant association between mosquito-related knowledge and control practices indicates higher knowledge linked to effective practices, particularly among female workers and those who were recently infected with malaria. Concurrently, there were notable challenges regarding sustainable preventive measures and larval control methods in construction settings.
CONCLUSION: Implementing effective mosquito control, including knowledge and practice on mosquito control together with vector control, is highly required to suppress the expanding mosquito population. It is recommended that employers provide continuous mosquito control education and training to their employees and reward them with incentives, while employees should comply with the guidelines set by their employers to ensure successful mosquito control and reduce the spread of mosquito-borne diseases in the construction industry.
METHODOLOGY: Data were collected using self-administered questionnaires from 1,914 respondents aged 18 and above by a marketing consulting firm via its online panel. The partial least squares structural equation modeling (PLS-SEM) technique was used to analyze the data.
RESULTS: Out of the 1,914 respondents, 55.9% reported having a continuance intention to vaccinate against COVID-19, similar to other developing countries. The multivariate analysis revealed that perceived usefulness and satisfaction significantly influenced individuals' continuance intention to vaccinate against COVID-19. Additionally, attitude was found to play a key role in influencing behavioral change among individuals towards their perceptions of continuously getting vaccinated against COVID-19.
CONCLUSIONS: By integrating three theoretical frameworks (i.e., HBM, TRA and ECM), this study showed that behavioral characteristics could provide insights towards continuance vaccination intention. Hence, policymakers and key stakeholders can develop effective public health strategies or interventions to encourage vaccine booster uptake by targeting behavioral factors such as perceived usefulness, attitude, satisfaction, and subjective norms.
METHODS: Patients who met the class I indication for implantable cardioverter-defibrillator (ICD) implantation according to guideline recommendations in 17 countries and regions underrepresented in previous trials were enrolled. Countries were stratified by the WHO regional classification. Patients were or were not implanted with an ICD at their discretion. The outcomes were all-cause mortality and SCD.
RESULTS: We enrolled 4222 patients, and 3889 patients were included in the analysis. The mean follow-up period was 21.6 ± 10.2 months. There were 433 (11.1%) instances of all-cause mortality and 117 (3.0%) cases of SCD. All-cause mortality was highest in primary prevention (PP) patients from Southeast Asia and secondary prevention (SP) patients from the Middle East and Africa. The SCD rates among PP and SP patients were both highest in South Asia. Multivariate Cox regression modelling demonstrated that in addition to the independent predictors identified in previous studies, both geographic region and ICD use were associated with all-cause mortality in patients with high SCD risk. Primary prophylactic ICD implantation was associated with a 36% (HR = 0.64, 95% CI 0.531-0.802, p
METHODS: Jom Mama was a non-blinded, randomised controlled trial (RCT) conducted in Seremban, Malaysia, over a period of 33 weeks, covering six contact points between trained community health workers and newly married couples before the conception of a first child. Out of 2075 eligible nulliparous women, 549 participated and 305 completed the intervention, with 145 women in the intervention and 160 in the control group. The intervention group received a complex behavioural change intervention, combining behaviour change communication provided by community health promoters and access to a habit formation mobile application, while the control group received the standard care provided by public health clinics in Malaysia. The primary outcome was a change in the woman's waist circumference. Secondary outcomes were anthropometric and metabolic measures, dietary intake (Food Frequency Questionnaire, FFQ), physical activity (International Physical Activity Questionnaire, IPAQ) and mental health (Depression Anxiety Stress Scale, DASS 21). An extensive process evaluation was conducted alongside the trial in order to aid the interpretation of the main findings.
RESULTS: There were no significant differences of change in the woman's waist circumference between intervention and control groups at the start and end of the intervention. While the weight, waist circumference and Body Mass Index (BMI) of women in both groups increased, there was a significantly lower increase in the intervention vs the control group over the period of the trial among women who are obese (0.1 kg vs 1.7 kg; P = 0.023, in the intervention and control group respectively). In terms of BMI, the obese intervention subgroup showed a slight reduction (0.01) compared to the obese control subgroup whose BMI increased by 0.7 (P = 0.015). There were no changes in the other secondary outcomes.
CONCLUSIONS: The Jom Mama pre-conception intervention did not lead to a reduction in waist circumference or significant changes in other secondary outcomes over the eight months prior to conception. However, there was a significantly smaller weight gain in the intervention vs the control group, predominantly in women with pre-existing obesity.
METHOD: The online survey was conducted among the residents of Sindh, Pakistan, in July 2021 through a survey tool designed using Google Forms and sent to the population through various social media.
RESULTS: Of 926 study participants, 59.0% were male, and 68.6% were aged between 18 and 31 years. Higher percentages of responses were recorded from the Hyderabad division (37.5%), and 60.0% of respondents were graduates, with 34.8% of them in the private sector. The results showed that 36.4% of respondents had good knowledge, and 30.3% had a positive attitude toward COVID-19 vaccination. Almost 77% of respondents perceived that everyone should get vaccinated in the country and those health care workers on priority. A majority (80.8%) of respondents were willing to accept COVID-19 vaccination.
CONCLUSION: Despite having insufficient knowledge and a low percentage of positive attitude public in Sindh are willing to be vaccinated. Based on this finding, more effort has to be done to promote vaccination among the public, especially among the less educated population.
METHODS: This prospective, multicentre, open-label, randomised, phase 3a trial (explorer8) was conducted at 69 investigational sites in 31 countries. Eligible patients were male, aged 12 years or older, and had congenital severe haemophilia A or moderate or severe haemophilia B without inhibitors and with documented treatment with clotting factor concentrate in the 24 weeks before screening. The trial was paused because of non-fatal thromboembolic events in three patients (two from this trial [explorer8] and one from a related trial in haemophilia with inhibitors [explorer7; NCT04083781]) and restarted with mitigation measures, including a revised dosing regimen of subcutaneous concizumab at 1·0 mg/kg loading dose on day 1 and subsequent daily doses of 0·20 mg/kg from day 2, with options to decrease to 0·15 mg/kg, stay on 0·20 mg/kg, or increase to 0·25 mg/kg on the basis of concizumab plasma concentration measured after 4 weeks on concizumab. Patients recruited after treatment restart were randomly assigned 1:2 using an interactive web response system to receive no prophylaxis and continue on-demand clotting factor (group 1) or concizumab prophylaxis (group 2). The primary endpoints were the number of treated spontaneous and traumatic bleeding episodes for patients with haemophilia A and haemophilia B separately, assessed at the confirmatory analysis cutoff in randomly assigned patients. Analyses were by intention-to-treat. There were two additional groups containing non-randomly-assigned patients: group 3 contained patients who entered the trial before the trial pause and were receiving concizumab in the phase 2 trial (explorer5; NCT03196297), and group 4 contained patients who received previous clotting factor concentrate prophylaxis or on-demand treatment in the non-interventional trial (explorer6; NCT03741881), patients randomly assigned to groups 1 or 2 before the treatment pause, and patients from explorer5 enrolled after the treatment pause. The safety analysis set contained all patients who received concizumab. Superiority of concizumab over no prophylaxis was established if the two-sided 95% CI of the treatment ratio was less than 1 for haemophilia A and for haemophilia B. This trial is registered with ClinicalTrials.gov, NCT04082429, and its extension part is ongoing.
FINDINGS: Patients were recruited between Nov 13, 2019 and Nov 30, 2021; the cutoff date for the analyses presented was July 12, 2022. 173 patients were screened, of whom 148 (86%) were randomly assigned or allocated to the four groups in the study after trial restart on Sept 30, 2020 (nine with haemophilia A and 12 with haemophilia B in group 1; 18 with haemophilia A and 24 with haemophilia B in group 2; nine with haemophilia A in group 3; and 46 with haemophilia A and 30 with haemophilia B in group 4). The estimated mean annualised bleeding rate ratio for treated spontaneous and traumatic bleeding episodes during concizumab prophylaxis versus no prophylaxis was 0·14 (95% CI 0·07-0·29; p<0·0001) for patients with haemophilia A and 0·21 (0·10-0·45; p<0·0001) for patients with haemophilia B. The most frequent adverse events in patients who received concizumab were SARS-CoV-2 infection (19 [13%] of 151 patients), an increase in fibrin D-dimers (12 [8%] patients), and upper respiratory tract infection (ten [7%] patients). There was one fatal adverse event possibly related to treatment (intra-abdominal haemorrhage in a patient from group 4 with haemophilia A with a long-standing history of hypertension). No thromboembolic events were reported between the trial restart and confirmatory analysis cutoff.
INTERPRETATION: Concizumab was effective in reducing the bleeding rate compared with no prophylaxis and was considered safe in patients with haemophilia A or B without inhibitors. The results of this trial suggest that concizumab has the potential to be one of the first subcutaneous treatment options for patients with haemophilia B without inhibitors.
FUNDING: Novo Nordisk.
METHODS: We propose a type III hybrid implementation/effectiveness interventional cohort trial in 35 ICUs in up to 11 low- and middle- income countries. The study intervention is a structured review of antimicrobial prescriptions as recommended by the World Health Organisation. Strategies to support stakeholder-led implementation include development of local protocols, registry-enabled audit and feedback, and education. Evaluation of implementation, and the determinants of its success, is informed by the RE-AIM framework and the Consolidated Framework for Implementation Research respectively. The primary outcome is a composite measure of fidelity, reach and adoption. Secondary outcomes describe the effectiveness of the intervention on improving antimicrobial prescribing. Qualitative interviews will assess relevant implementation acceptability, adaptations and maintenance. A baseline survey will investigate ICU-level antimicrobial stewardship structures and processes.
DISCUSSION: This study addresses global policy priorities by supporting implementation research of antimicrobial stewardship, and strengthening associated healthcare professional competencies. It does this in a setting where improvement is sorely needed: low- and middle- income country ICUs. The study will also describe the influence of pre-existing antimicrobial stewardship structures and processes on implementation and improve understanding about the efficacy of strategies to overcome barriers to implementation in these settings.
TRIAL REGISTRATION: This study protocol has been registered with ClinicalTrials.gov (ref NCT06666738) on 31 Oct 2004. https://clinicaltrials.gov/study/NCT06666738?term=NCT06666738&rank=1 .