Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Predictors of unanticipated admission following ambulatory surgery in the pediatric population: a retrospective case-control study.

BACKGROUND: Ambulatory surgery plays an important role in pediatric anesthesia. However, it is difficult to predict which patients will experience complications. Age >80, ASA class 3 or 4, duration of surgery >3 h, and BMI 30-35 are independent predictors of unanticipated admission in adults. In this study, we retrospectively evaluate risk factors for unanticipated admission, following ambulatory surgery in children. METHODS: All ambulatory patients requiring unanticipated admission between 2005 and 2013 were compared to a random sample of patients not requiring admission in this case-control study. Demographic data, surgical information, medications, intraoperative events, and patient comorbidities were collected from both groups. The reason for admission was classified according to five subtypes. Multiple conditional logistic regression was used to assess factors associated with unanticipated admissions. RESULTS: The incidence of unanticipated admission was 0.97% (213). Of these, 47% (98) was anesthesia related. Age <2 years (odds ratio [OR] 4.26 95% CI 1.19-15.25), ASA 3 class (OR 3.77 95% CI 1.46-9.71), duration of surgery >1 h (OR 6.54 95% CI 3.47-12.33), completion of surgery >3 pm (OR 2.17 95% CI 1.05-4.51), orthopedic (OR 2.52 95% CI 1.03-6.20), dental (OR 0.21 95% CI 0.06-0.81), ENT (OR 6.47 95% CI 2.99-14.03) surgery, intraoperative events (OR 4.45 95% CI 1.35-18.12), and OSA (OR 6.32 95% CI 1.54-25.94) were factors associated with unanticipated admission. CONCLUSION: The incidence of unanticipated admission in children following ambulatory surgery is low. Age, ASA class, duration, and time of completion of surgery are predictors common to pediatrics and adults. Interestingly, intraoperative complications, OSA, and type of surgery (ENT, orthopedic, dental) are specific to pediatrics.

Predictors of unanticipated admission following ambulatory surgery: a retrospective case-control study.

PURPOSE: The primary objectives of this historical case-control study were to evaluate the incidence of and reasons and risk factors for adult unanticipated admissions in three tertiary care Canadian hospitals following ambulatory surgery. METHODS: A random sample of 200 patients requiring admission (cases) and 200 patients not requiring admission (controls) was taken from 20,657 ambulatory procedures was identified and compared. The following variables were included: demographics, reason for admission, type of anesthesia, surgical procedure, length of procedure, American Society of Anesthesiologists' (ASA) classification, surgical completion time, pre-anesthesia clinic, medical history, medications (classes), and perioperative complications. Multiple logistic regression analysis was used to assess factors associated with unanticipated admissions. RESULTS: The incidence of unanticipated admission following ambulatory surgery was 2.67%. The most common reasons for admission were surgical (40%), anesthetic (20%), and medical (19%). The following factors were found to be associated with an increased risk of unanticipated admission: length of surgery of one to three hours (odds ratio [OR] 16.70; 95% confidence interval [CI] 4.10 to 67.99) and length of surgery more than three hours (OR 4.26; 95% CI 2.40 to 7.55); ASA class III (OR 4.60; 95% CI 1.81 to 11.68); ASA class IV (OR 6.51; 95% CI 1.66 to 25.59); advanced age (> 80 yr) (OR 5.41; 95% CI 1.54 to 19.01); and body mass index (BMI) of 30-35 (OR 2.81; 95% CI 1.31 to 6.04). Current smoking status was found to be associated with a decreased likelihood of unanticipated admission (OR 0.44; 95% CI 0.23 to 0.83), as was monitored anesthesia care when compared with general anesthesia (OR 0.17; 95% CI 0.04 to 0.68) and plastic (OR 0.18; 95% CI 0.07 to 0.50), orthopedic (OR 0.16; 95% CI 0.08 to 0.33), and dental/ear-nose-throat surgery (OR 0.32; 95% CI 0.13 to 0.83) when compared with general surgery. Other comorbid conditions did not impact unanticipated admission. CONCLUSION: Unanticipated admission after ambulatory surgery occurs mainly due to surgical, anesthetic, and medical complications. Length of surgery more than one hour, high ASA class, advanced age, and increased BMI were all predictors. No specific comorbid illness was associated with an increased likelihood of unanticipated admission. These findings support continued use of the ASA classification as a marker of patient perioperative risk rather than attributing risk to a specific disease process.

The reporting of pilot and feasibility studies in the top dental specialty journals is suboptimal.

BACKGROUND: Pilot and feasibility studies (PAFS) are smaller investigations seeking to assess the feasibility of conducting a larger more definitive study. In late 2016, the CONSORT statement was extended to disseminate good practices for reporting of randomized pilot and feasibility trials. In this quality assurance review, we assessed whether PAFS in the top dental speciality journals adhere to good practices of conduct and reporting, by prioritizing assessment of feasibility and stating pre-defined progression criteria to inform the decision to pursue funding for a larger trial. METHODS: With the help of a librarian, we searched MEDLINE and EMBASE from 2017 to 2020, inclusive, for PAFS in the top 3 journals from each of the 10 dental specialties. We collected data on methodological and general characteristics of the studies, their objectives, and reporting of items recommended in the CONSORT extension. RESULTS: Of the 111 trials included, 51.4% (95% CI 41.7-61.0%) stated some indication of intent to assess feasibility while zero reported progression criteria; 74.8% (95% CI 65.6-82.5%) of trials used the terms "pilot" or "feasibility" in their titles and 82.9% (95% CI 74.6-89.4%) of studies stated there is a need for a future trial, but only 9.0% (95% CI 4.4-15.9%) stated intent to proceed to one. Most of the studies, 53.2% (95% CI 43.4-62.7%), reported hypothesis testing without cautioning readers on the generalizability of the results. Studies that used the terms "pilot" or "feasibility" in their title were less likely to have feasibility objectives, compared to trials that did not, with an odds ratio (OR) of 0.310 (95% CI 0.103-0.930; p = 0.037). Compared to trials that did not conduct hypothesis testing, trials that conducted hypothesis testing were significantly less likely to assess feasibility, among them, trials that cautioned readers on the generalizability of their results had an OR of 0.038 (95% CI 0.005-0.264; p < 0.001) and trials that did not caution readers on the generalizability of their results had an OR of 0.043 (95% CI 0.008-0.238; p = 0.001). CONCLUSION: Many PAFS in dentistry are not conducted with the intent of assessing feasibility, nor do they state progression criteria, and few report intent to proceed to a future trial. Misconceptions about PAFS can lead to them being poorly conducted and reported, which has economic and ethical implications. Research ethics boards, funding agencies, and journals need to raise their standards for the conduct and reporting of PAFS, and resources should be developed to address misconceptions and help guide researchers on the best practices for their conduct and reporting.

A pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solutions in open fractures (Aqueous-PREP): statistical analysis plan.

BACKGROUND: Approximately 1 in 10 patients with a surgically treated open fracture will develop a surgical site infection. The Aqueous-PREP trial will investigate the effect of 10% povidone-iodine versus 4% chlorhexidine in aqueous antiseptic solutions in reducing infections after open fracture surgery. The study protocol was published in April 2020. METHODS AND DESIGN: The Aqueous-PREP trial is a pragmatic, multicenter, open-label, randomized multiple period cluster crossover trial. Each participating cluster is randomly assigned in a 1:1 ratio to provide 1 of the 2 study interventions on all eligible patients during a study period. The intervention periods are 2 months in length. After completing a 2-month period, the participating cluster crosses over to the alternative intervention. We plan to enroll a minimum of 1540 patients at 14 sites. RESULTS: The primary outcome is surgical site infection guided by the Centers for Disease Control and Prevention's National Healthcare Safety Network reporting criteria (2017). All participants' surgical site infection surveillance period will end 30 days after definitive fracture management surgery for superficial infections and 90 days after definitive fracture management surgery for deep incisional or organ/space infections [1]. The secondary outcome is an unplanned fracture-related reoperation within 12 months of the fracture. CONCLUSION: This manuscript serves as the formal statistical analysis plan (version 1.0) for the Aqueous-PREP trial. The statistical analysis plan was completed on February 28, 2022.

Optimising the management of childhood acute diarrhoeal disease using a rapid test-and- treat strategy and/or Lactobacillus reuteri DSM 17938: a multicentre, randomised, controlled, factorial trial in Botswana.

INTRODUCTION: The study aim was to determine if rapid enteric diagnostics followed by the provision of targeted antibiotic therapy ('test-and-treat') and/or Lactobacillus reuteri DSM 17938 would improve outcomes in children hospitalised in Botswana with acute gastroenteritis. METHODS: This was a multicentre, randomised, factorial, controlled, trial. Children aged 2-60 months admitted for acute non-bloody diarrhoea to four hospitals in southern Botswana were eligible. Participants were assigned to treatment groups by web-based block randomisation. Test-and-treat results were not blinded, but participants and research staff were blinded to L. reuteri/placebo assignment; this was dosed as 1×108 cfu/mL by mouth daily and continued for 60 days. The primary outcome was 60-day age-standardised height (HAZ) adjusted for baseline HAZ. All analyses were by intention to treat. The trial was registered at Clinicaltrials.gov. RESULTS: Recruitment began on 12 June 2016 and continued until 24 October 2018. There were 66 participants randomised to the test-and-treat plus L. reuteri group, 68 randomised to the test-and-treat plus placebo group, 69 to the standard care plus L. reuteri group and 69 to the standard care plus placebo group. There was no demonstrable impact of the test-and-treat intervention (mean increase of 0.01 SD, 95% CI -0.14 to 0.16 SD) or the L. reuteri intervention (mean decrease of 0.07 SD, 95% CI -0.22 to 0.08 SD) on adjusted HAZ at 60 days. CONCLUSIONS: In children hospitalised for acute gastroenteritis in Botswana, neither a test-and-treat algorithm targeting enteropathogens, nor a 60-day course of L. reuteri DSM 17938, were found to markedly impact linear growth or other important outcomes. We cannot exclude the possibility that test-and-treat will improve the care of children with significant enteropathogens (such as Shigella) in their stool. TRIAL REGISTRATION NUMBER: NCT02803827.

Effects of piezocision in orthodontic tooth movement: A systematic review of comparative studies.

BACKGROUND: The aim of this systematic review was to evaluate the effects of piezocision in accelerating orthodontic tooth movement (OTM) and its possible adverse effects. MATERIAL AND METHODS: The Databases Medline, Embase, CENTRAL and LILACS were searched until March 2019, for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that used piezocision associated with orthodontic treatment. A manual search was also performed. The search, studies selection, assessment of risk of bias and data collection were carried out by two independent reviewers. RESULTS: Eleven publications were included in this review (4 CCTs and 7 RCTs). No study presented low risk of bias. Different types of tooth movement were evaluated: lower anterior alignment, en-masse retraction, overall orthodontic treatment and canine distalization. A total of 240 participants were analyzed in the included studies. Seven studies found significant acceleration in the piezocision group, while two studies found no differences. Adverse effects regarding patient's satisfaction, pain perception, or worsening of periodontal parameters were not observed. There was no consensus concerning anchorage loss and root resorption. CONCLUSIONS: The literature does not provide high-quality evidence to confirm that Piezocision results in significant OTM acceleration. Therefore, high-quality RCTs should be conducted to allow reliable conclusions about the effects of piezocision in orthodontics. Key words:Piezosurgery, tooth movement techniques, orthodontics.

Deliberate hypotension in orthopedic surgery reduces blood loss and transfusion requirements: a meta-analysis of randomized controlled trials.

PURPOSE: To determine if deliberate hypotension decreases blood loss and transfusion requirements in patients undergoing orthopedic surgery, a systematic review of all randomized trials addressing this issue was undertaken. METHODS: Electronic databases, citations lists and review articles were searched for potential articles. Relevant articles met the following inclusion criteria: English language, humans undergoing orthopedic surgery, deliberate hypotension used by any method, intraoperative blood loss measured as an outcome, and the trial methodology being randomized and controlled. Four outcomes were analyzed, including estimated blood loss, blood transfused, surgery duration, and quality of the surgical field. For all analyses, the random-effects model was used. RESULTS: Seventeen articles met the inclusion criteria. The surgeries studied included total hip arthroplasty (seven), orthognathic surgery (eight), total knee arthroplasty (one) and spinal fusion (one). A total of 636 patients were randomized across all studies. For blood loss, the overall weighted mean difference favoured treatment, with a savings of about 287 mL of blood [95% confidence interval (CI): -447, -127]. The mean differences also showed a statistically significant benefit for deliberate hypotension in reducing transfusion requirements (-667 mL of blood transfused; 95% CI: -963, -370). Deliberate hypotension was not shown to reduce the duration of surgery (-1.9 min of surgery; 95% CI: -7.2, 3.5) or improve surgical conditions (surgical field quality rating -0.5; 95% CI: -1.1, 0.2). CONCLUSION: This review provides some support for the use of deliberate hypotension in reducing blood loss and transfusion requirements in orthopedic surgery, but these results are tempered by the small sample sizes and poor methodological quality of published studies.