OBJECTIVES: To assess the benefits and harms of automated oxygen delivery systems, embedded within a ventilator or oxygen delivery device, for preterm infants with respiratory dysfunction who require respiratory support or supplemental oxygen therapy.
SEARCH METHODS: We searched CENTRAL, MEDLINE, CINAHL, and clinical trials databases without language or publication date restrictions on 23 January 2023. We also checked the reference lists of retrieved articles for other potentially eligible trials.
SELECTION CRITERIA: We included randomised controlled trials and randomised cross-over trials that compared automated oxygen delivery versus manual oxygen delivery, or that compared different automated oxygen delivery systems head-to-head, in preterm infants (born before 37 weeks' gestation).
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were time (%) in desired oxygen saturation (SpO2) range, all-cause in-hospital mortality by 36 weeks' postmenstrual age, severe retinopathy of prematurity (ROP), and neurodevelopmental outcomes at approximately two years' corrected age. We expressed our results using mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence.
MAIN RESULTS: We included 18 studies (27 reports, 457 infants), of which 13 (339 infants) contributed data to meta-analyses. We identified 13 ongoing studies. We evaluated three comparisons: automated oxygen delivery versus routine manual oxygen delivery (16 studies), automated oxygen delivery versus enhanced manual oxygen delivery with increased staffing (three studies), and one automated system versus another (two studies). Most studies were at low risk of bias for blinding of personnel and outcome assessment, incomplete outcome data, and selective outcome reporting; and half of studies were at low risk of bias for random sequence generation and allocation concealment. However, most were at high risk of bias in an important domain specific to cross-over trials, as only two of 16 cross-over trials provided separate outcome data for each period of the intervention (before and after cross-over). Automated oxygen delivery versus routine manual oxygen delivery Automated delivery compared with routine manual oxygen delivery probably increases time (%) in the desired SpO2 range (MD 13.54%, 95% CI 11.69 to 15.39; I2 = 80%; 11 studies, 284 infants; moderate-certainty evidence). No studies assessed in-hospital mortality. Automated oxygen delivery compared to routine manual oxygen delivery may have little or no effect on risk of severe ROP (RR 0.24, 95% CI 0.03 to 1.94; 1 study, 39 infants; low-certainty evidence). No studies assessed neurodevelopmental outcomes. Automated oxygen delivery versus enhanced manual oxygen delivery There may be no clear difference in time (%) in the desired SpO2 range between infants who receive automated oxygen delivery and infants who receive manual oxygen delivery (MD 7.28%, 95% CI -1.63 to 16.19; I2 = 0%; 2 studies, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. Revised closed-loop automatic control algorithm (CLACfast) versus original closed-loop automatic control algorithm (CLACslow) CLACfast allowed up to 120 automated adjustments per hour, whereas CLACslow allowed up to 20 automated adjustments per hour. CLACfast may result in little or no difference in time (%) in the desired SpO2 range compared to CLACslow (MD 3.00%, 95% CI -3.99 to 9.99; 1 study, 19 infants; low-certainty evidence). No studies assessed in-hospital mortality, severe ROP, or neurodevelopmental outcomes. OxyGenie compared to CLiO2 Data from a single small study were presented as medians and interquartile ranges and were not suitable for meta-analysis.
AUTHORS' CONCLUSIONS: Automated oxygen delivery compared to routine manual oxygen delivery probably increases time in desired SpO2 ranges in preterm infants on respiratory support. However, it is unclear whether this translates into important clinical benefits. The evidence on clinical outcomes such as severe retinopathy of prematurity are of low certainty, with little or no differences between groups. There is insufficient evidence to reach any firm conclusions on the effectiveness of automated oxygen delivery compared to enhanced manual oxygen delivery or CLACfast compared to CLACslow. Future studies should include important short- and long-term clinical outcomes such as mortality, severe ROP, bronchopulmonary dysplasia/chronic lung disease, intraventricular haemorrhage, periventricular leukomalacia, patent ductus arteriosus, necrotising enterocolitis, and long-term neurodevelopmental outcomes. The ideal study design for this evaluation is a parallel-group randomised controlled trial. Studies should clearly describe staffing levels, especially in the manual arm, to enable an assessment of reproducibility according to resources in various settings. The data of the 13 ongoing studies, when made available, may change our conclusions, including the implications for practice and research.
METHODS: Neonatal trials including ≥100 participants/arm published between 2015 and 2020 with at least 1 primary outcome from a neonatal core outcome set were eligible. Raters recruited from Cochrane Neonatal were trained to evaluate the trials' primary outcome reporting completeness using relevant items from Consolidated Standards of Reporting Trials 2010 and Consolidated Standards of Reporting Trials-Outcomes 2022 pertaining to the reporting of the definition, selection, measurement, analysis, and interpretation of primary trial outcomes. All trial reports were assessed by 3 raters. Assessments and discrepancies between raters were analyzed.
RESULTS: Outcome-reporting evaluations were completed for 36 included neonatal trials by 39 raters. Levels of outcome reporting completeness were highly variable. All trials fully reported the primary outcome measurement domain, statistical methods used to compare treatment groups, and participant flow. Yet, only 28% of trials fully reported on minimal important difference, 24% on outcome data missingness, 66% on blinding of the outcome assessor, and 42% on handling of outcome multiplicity.
CONCLUSIONS: Primary outcome reporting in neonatal trials often lacks key information needed for interpretability of results, knowledge synthesis, and evidence-informed decision-making in neonatology. Use of existing outcome-reporting guidelines by trialists, journals, and peer reviewers will enhance transparent reporting of neonatal trials.
METHODS: Neonatal trials including >100 participants per arm published between 2015 to 2020 with a primary outcome included in the Neonatal Core Outcome Set were identified. Primary outcome reporting was reviewed using CONSORT 2010 and CONSORT-Outcomes 2022 guidelines by assessors recruited from Cochrane Neonatal. Examples of clear and complete outcome reporting were identified with verbatim text extracted from trial reports.
RESULTS: Thirty-six trials were reviewed by 39 assessors. Examples of good reporting for CONSORT 2010 and CONSORT-Outcomes 2022 criteria were identified and subdivided into 3 outcome categories: "survival," "short-term neonatal complications," and "long-term developmental outcomes" depending on the core outcomes to which they relate. These examples are presented to strengthen future research reporting.
CONCLUSIONS: We have identified examples of good trial outcome reporting. These illustrate how important neonatal outcomes should be reported to meet the CONSORT 2010 and CONSORT-Outcomes 2022 guidelines. Emulating these examples will improve the transmission of information relating to outcomes and reduce associated research waste.
OBJECTIVE: We aimed to determine the prevalence of various cancers in NAFLD patients and the association between NAFLD and cancer.
METHODS: We searched PubMed, ProQuest, Scopus, and Web of Science from database inception to March 2022 to identify eligible studies reporting the prevalence of NAFLD and the risk of incident cancers among adult individuals (aged ≥18 years). Data from selected studies were extracted, and meta-analysis was performed using random effects models to obtain the pooled prevalence with the 95% CI. The quality of the evidence was assessed with the Newcastle-Ottawa Scale.
RESULTS: We identified 11 studies that met our inclusion criteria, involving 222,523 adults and 3 types of cancer: hepatocellular carcinoma (HCC), breast cancer, and other types of extrahepatic cancer. The overall pooled prevalence of NAFLD and cancer was 26% (95% CI 16%-35%), while 25% of people had NAFLD and HCC (95% CI 7%-42%). NAFLD and breast cancer had the highest prevalence out of the 3 forms of cancer at 30% (95% CI 14%-45%), while the pooled prevalence for NAFLD and other cancers was 21% (95% CI 12%-31%).
CONCLUSIONS: The review suggests that people with NAFLD may be at an increased risk of cancer that might not affect not only the liver but also other organs, such as the breast and bile duct. The findings serve as important evidence for policymakers to evaluate and recommend measures to reduce the prevalence of NAFLD through lifestyle and environmental preventive approaches.
TRIAL REGISTRATION: PROSPERO CRD42022321946; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=321946.
OBJECTIVES: To assess the effects of interventions for people with type 2 diabetes fasting during Ramadan.
SEARCH METHODS: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, WHO ICTRP and ClinicalTrials.gov (29 June 2022) without language restrictions.
SELECTION CRITERIA: Randomised controlled trials (RCTs) conducted during Ramadan that evaluated all pharmacological or behavioural interventions in Muslims with T2DM.
DATA COLLECTION AND ANALYSIS: Two authors screened and selected records, assessed risk of bias and extracted data independently. Discrepancies were resolved by a third author. For meta-analyses we used a random-effects model, with risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with their associated 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach.
MAIN RESULTS: We included 17 RCTs with 5359 participants, with a four-week study duration and at least four weeks of follow-up. All studies had at least one high-risk domain in the risk of bias assessment. Four trials compared dipeptidyl-peptidase-4 (DPP-4) inhibitors with sulphonylurea. DPP-4 inhibitors may reduce hypoglycaemia compared to sulphonylureas (85/1237 versus 165/1258, RR 0.53, 95% CI 0.41 to 0.68; low-certainty evidence). Serious hypoglycaemia was similar between groups (no events were reported in two trials; 6/279 in the DPP-4 versus 4/278 in the sulphonylurea group was reported in one trial, RR 1.49, 95% CI 0.43 to 5.24; very low-certainty evidence). The evidence was very uncertain about the effects of DPP-4 inhibitors on adverse events other than hypoglycaemia (141/1207 versus 157/1219, RR 0.90, 95% CI 0.52 to 1.54) and HbA1c changes (MD -0.11%, 95% CI -0.57 to 0.36) (very low-certainty evidence for both outcomes). No deaths were reported (moderate-certainty evidence). Health-related quality of life (HRQoL) and treatment satisfaction were not evaluated. Two trials compared meglitinides with sulphonylurea. The evidence is very uncertain about the effect on hypoglycaemia (14/133 versus 21/140, RR 0.72, 95% CI 0.40 to 1.28) and HbA1c changes (MD 0.38%, 95% CI 0.35% to 0.41%) (very low-certainty evidence for both outcomes). Death, serious hypoglycaemic events, adverse events, treatment satisfaction and HRQoL were not evaluated. One trial compared sodium-glucose co-transporter-2 (SGLT-2) inhibitors with sulphonylurea. SGLT-2 may reduce hypoglycaemia compared to sulphonylurea (4/58 versus 13/52, RR 0.28, 95% CI 0.10 to 0.79; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (one event reported in both groups, RR 0.90, 95% CI 0.06 to 13.97) and adverse events other than hypoglycaemia (20/58 versus 18/52, RR 1.00, 95% CI 0.60 to 1.67) (very low-certainty evidence for both outcomes). SGLT-2 inhibitors result in little or no difference in HbA1c (MD 0.27%, 95% CI -0.04 to 0.58; 1 trial, 110 participants; low-certainty evidence). Death, treatment satisfaction and HRQoL were not evaluated. Three trials compared glucagon-like peptide 1 (GLP-1) analogues with sulphonylurea. GLP-1 analogues may reduce hypoglycaemia compared to sulphonylurea (20/291 versus 48/305, RR 0.45, 95% CI 0.28 to 0.74; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (0/91 versus 1/91, RR 0.33, 95% CI 0.01 to 7.99; very low-certainty evidence). The evidence suggests that GLP-1 analogues result in little to no difference in adverse events other than hypoglycaemia (78/244 versus 55/255, RR 1.50, 95% CI 0.86 to 2.61; very low-certainty evidence), treatment satisfaction (MD -0.18, 95% CI -3.18 to 2.82; very low-certainty evidence) or change in HbA1c (MD -0.04%, 95% CI -0.45% to 0.36%; 2 trials, 246 participants; low-certainty evidence). Death and HRQoL were not evaluated. Two trials compared insulin analogues with biphasic insulin. The evidence was very uncertain about the effects of insulin analogues on hypoglycaemia (47/256 versus 81/244, RR 0.43, 95% CI 0.13 to 1.40) and serious hypoglycaemia (4/131 versus 3/132, RR 1.34, 95% CI 0.31 to 5.89) (very low-certainty evidence for both outcomes). The evidence was very uncertain for the effect of insulin analogues on adverse effects other than hypoglycaemia (109/256 versus 114/244, RR 0.83, 95% CI 0.44 to 1.56; very low-certainty evidence), all-cause mortality (1/131 versus 0/132, RR 3.02, 95% CI 0.12 to 73.53; very low-certainty evidence) and HbA1c changes (MD 0.03%, 95% CI -0.17% to 0.23%; 1 trial, 245 participants; very low-certainty evidence). Treatment satisfaction and HRQoL were not evaluated. Two trials compared telemedicine with usual care. The evidence was very uncertain about the effect of telemedicine on hypoglycaemia compared with usual care (9/63 versus 23/58, RR 0.42, 95% CI 0.24 to 0.74; very low-certainty evidence), HRQoL (MD 0.06, 95% CI -0.03 to 0.15; very low-certainty evidence) and HbA1c change (MD -0.84%, 95% CI -1.51% to -0.17%; very low-certainty evidence). Death, serious hypoglycaemia, AEs other than hypoglycaemia and treatment satisfaction were not evaluated. Two trials compared Ramadan-focused patient education with usual care. The evidence was very uncertain about the effect of Ramadan-focused patient education on hypoglycaemia (49/213 versus 42/209, RR 1.17, 95% CI 0.82 to 1.66; very low-certainty evidence) and HbA1c change (MD -0.40%, 95% CI -0.73% to -0.06%; very low-certainty evidence). Death, serious hypoglycaemia, adverse events other than hypoglycaemia, treatment satisfaction and HRQoL were not evaluated. One trial compared drug dosage reduction with usual care. The evidence is very uncertain about the effect of drug dosage reduction on hypoglycaemia (19/452 versus 52/226, RR 0.18, 95% CI 0.11 to 0.30; very low-certainty evidence). No participants experienced adverse events other than hypoglycaemia during the study (very low-certainty evidence). Death, serious hypoglycaemia, treatment satisfaction, HbA1c change and HRQoL were not evaluated.
AUTHORS' CONCLUSIONS: There is no clear evidence of the benefits or harms of interventions for individuals with T2DM who fast during Ramadan. All results should be interpreted with caution due to concerns about risk of bias, imprecision and inconsistency between studies, which give rise to low- to very low-certainty evidence. Major outcomes, such as mortality, health-related quality of life and severe hypoglycaemia, were rarely evaluated. Sufficiently powered studies that examine the effects of various interventions on these outcomes are needed.
OBJECTIVES: To assess the effects of low glycaemic index or low glycaemic load diets on weight loss in people with overweight or obesity.
SEARCH METHODS: We searched CENTRAL, MEDLINE, one other database, and two clinical trials registers from their inception to 25 May 2022. We did not apply any language restrictions.
SELECTION CRITERIA: We included RCTs with a minimum duration of eight weeks comparing low GI/GL diets to higher GI/GL diets or any other diets in people with overweight or obesity.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We conducted two main comparisons: low GI/GL diets versus higher GI/GL diets and low GI/GL diets versus any other diet. Our main outcomes included change in body weight and body mass index, adverse events, health-related quality of life, and mortality. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS: In this updated review, we included 10 studies (1210 participants); nine were newly-identified studies. We included only one study from the previous version of this review, following a revision of inclusion criteria. We listed five studies as 'awaiting classification' and one study as 'ongoing'. Of the 10 included studies, seven compared low GI/GL diets (233 participants) with higher GI/GL diets (222 participants) and three studies compared low GI/GL diets (379 participants) with any other diet (376 participants). One study included children (50 participants); one study included adults aged over 65 years (24 participants); the remaining studies included adults (1136 participants). The duration of the interventions varied from eight weeks to 18 months. All trials had an unclear or high risk of bias across several domains. Low GI/GL diets versus higher GI/GL diets Low GI/GL diets probably result in little to no difference in change in body weight compared to higher GI/GL diets (mean difference (MD) -0.82 kg, 95% confidence interval (CI) -1.92 to 0.28; I2 = 52%; 7 studies, 403 participants; moderate-certainty evidence). Evidence from four studies reporting change in body mass index (BMI) indicated low GI/GL diets may result in little to no difference in change in BMI compared to higher GI/GL diets (MD -0.45 kg/m2, 95% CI -1.02 to 0.12; I2 = 22%; 186 participants; low-certainty evidence)at the end of the study periods. One study assessing participants' mood indicated that low GI/GL diets may improve mood compared to higher GI/GL diets, but the evidence is very uncertain (MD -3.5, 95% CI -9.33 to 2.33; 42 participants; very low-certainty evidence). Two studies assessing adverse events did not report any adverse events; we judged this outcome to have very low-certainty evidence. No studies reported on all-cause mortality. For the secondary outcomes, low GI/GL diets may result in little to no difference in fat mass compared to higher GI/GL diets (MD -0.86 kg, 95% CI -1.52 to -0.20; I2 = 6%; 6 studies, 295 participants; low certainty-evidence). Similarly, low GI/GL diets may result in little to no difference in fasting blood glucose level compared to higher GI/GL diets (MD 0.12 mmol/L, 95% CI 0.03 to 0.21; I2 = 0%; 6 studies, 344 participants; low-certainty evidence). Low GI/GL diets versus any other diet Low GI/GL diets probably result in little to no difference in change in body weight compared to other diets (MD -1.24 kg, 95% CI -2.82 to 0.34; I2 = 70%; 3 studies, 723 participants; moderate-certainty evidence). The evidence suggests that low GI/GL diets probably result in little to no difference in change in BMI compared to other diets (MD -0.30 kg in favour of low GI/GL diets, 95% CI -0.59 to -0.01; I2 = 0%; 2 studies, 650 participants; moderate-certainty evidence). Two adverse events were reported in one study: one was not related to the intervention, and the other, an eating disorder, may have been related to the intervention. Another study reported 11 adverse events, including hypoglycaemia following an oral glucose tolerance test. The same study reported seven serious adverse events, including kidney stones and diverticulitis. We judged this outcome to have low-certainty evidence. No studies reported on health-related quality of life or all-cause mortality. For the secondary outcomes, none of the studies reported on fat mass. Low GI/GL diets probably do not reduce fasting blood glucose level compared to other diets (MD 0.03 mmol/L, 95% CI -0.05 to 0.12; I2 = 0%; 3 studies, 732 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: The current evidence indicates there may be little to no difference for all main outcomes between low GI/GL diets versus higher GI/GL diets or any other diet. There is insufficient information to draw firm conclusions about the effect of low GI/GL diets on people with overweight or obesity. Most studies had a small sample size, with only a few participants in each comparison group. We rated the certainty of the evidence as moderate to very low. More well-designed and adequately-powered studies are needed. They should follow a standardised intervention protocol, adopt objective outcome measurement since blinding may be difficult to achieve, and make efforts to minimise loss to follow-up. Furthermore, studies in people from a wide range of ethnicities and with a wide range of dietary habits, as well as studies in low- and middle-income countries, are needed.
OBJECTIVES: To systematically evaluate the safety and efficacy of different antiseptic solutions in preventing CRBSI and other related outcomes in neonates with CVC.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries up to 22 April 2022. We checked reference lists of included trials and systematic reviews that related to the intervention or population examined in this Cochrane Review. SELECTION CRITERIA: Randomised controlled trials (RCTs) or cluster-RCTs were eligible for inclusion in this review if they were performed in the neonatal intensive care unit (NICU), and were comparing any antiseptic solution (single or in combination) against any other type of antiseptic solution or no antiseptic solution or placebo in preparation for central catheter insertion. We excluded cross-over trials and quasi-RCTs.
DATA COLLECTION AND ANALYSIS: We used the standard methods from Cochrane Neonatal. We used the GRADE approach to assess the certainty of the evidence.
MAIN RESULTS: We included three trials that had two different comparisons: 2% chlorhexidine in 70% isopropyl alcohol (CHG-IPA) versus 10% povidone-iodine (PI) (two trials); and CHG-IPA versus 2% chlorhexidine in aqueous solution (CHG-A) (one trial). A total of 466 neonates from level III NICUs were evaluated. All included trials were at high risk of bias. The certainty of the evidence for the primary and some important secondary outcomes ranged from very low to moderate. There were no included trials that compared antiseptic skin solutions with no antiseptic solution or placebo. CHG-IPA versus 10% PI Compared to PI, CHG-IPA may result in little to no difference in CRBSI (risk ratio (RR) 1.32, 95% confidence interval (CI) 0.53 to 3.25; risk difference (RD) 0.01, 95% CI -0.03 to 0.06; 352 infants, 2 trials, low-certainty evidence) and all-cause mortality (RR 0.88, 95% CI 0.46 to 1.68; RD -0.01, 95% CI -0.08 to 0.06; 304 infants, 1 trial, low-certainty evidence). The evidence is very uncertain about the effect of CHG-IPA on CLABSI (RR 1.00, 95% CI 0.07 to 15.08; RD 0.00, 95% CI -0.11 to 0.11; 48 infants, 1 trial; very low-certainty evidence) and chemical burns (RR 1.04, 95% CI 0.24 to 4.48; RD 0.00, 95% CI -0.03 to 0.03; 352 infants, 2 trials, very low-certainty evidence), compared to PI. Based on a single trial, infants receiving CHG-IPA appeared less likely to develop thyroid dysfunction compared to PI (RR 0.05, 95% CI 0.00 to 0.85; RD -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 10 to 50; 304 infants). Neither of the two included trials assessed the outcome of premature central line removal or the proportion of infants or catheters with exit-site infection. CHG-IPA versus CHG-A The evidence suggests CHG-IPA may result in little to no difference in the rate of proven CRBSI when applied on the skin of neonates prior to central line insertion (RR 0.80, 95% CI 0.34 to 1.87; RD -0.05, 95% CI -0.22 to 0.13; 106 infants, 1 trial, low-certainty evidence) and CLABSI (RR 1.14, 95% CI 0.34 to 3.84; RD 0.02, 95% CI -0.12 to 0.15; 106 infants, 1 trial, low-certainty evidence), compared to CHG-A. Compared to CHG-A, CHG-IPA probably results in little to no difference in premature catheter removal (RR 0.91, 95% CI 0.26 to 3.19; RD -0.01, 95% CI -0.15 to 0.13; 106 infants, 1 trial, moderate-certainty evidence) and chemical burns (RR 0.98, 95% CI 0.47 to 2.03; RD -0.01, 95% CI -0.20 to 0.18; 114 infants, 1 trial, moderate-certainty evidence). No trial assessed the outcome of all-cause mortality and the proportion of infants or catheters with exit-site infection.
AUTHORS' CONCLUSIONS: Based on current evidence, compared to PI, CHG-IPA may result in little to no difference in CRBSI and mortality. The evidence is very uncertain about the effect of CHG-IPA on CLABSI and chemical burns. One trial showed a statistically significant increase in thyroid dysfunction with the use of PI compared to CHG-IPA. The evidence suggests CHG-IPA may result in little to no difference in the rate of proven CRBSI and CLABSI when applied on the skin of neonates prior to central line insertion. Compared to CHG-A, CHG-IPA probably results in little to no difference in chemical burns and premature catheter removal. Further trials that compare different antiseptic solutions are required, especially in low- and middle-income countries, before stronger conclusions can be made.
OBJECTIVE: This review aims to evaluate the effectiveness of nondrug interventions in reducing OIs among patients with hematological cancers.
METHODS: The PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase databases were searched on December 26, 2022, for all randomized controlled trials (RCTs). The primary endpoint was OIs. The quality of included studies was assessed by the Cochrane Risk-of-Bias tool.
RESULTS: A total of 6 studies were included in this review with 4 interventions: (1) types of mouthwash received, (2) presence of coating on central venous catheters (CVCs), (3) use of well-fitted masks, and (4) types of diet consumed. The results were presented in 8 different comparisons: (1) chlorhexidine-nystatin versus saline mouth rinse, (2) chlorhexidine versus saline mouth rinse, (3) nystatin versus saline mouth rinse, (4) chlorhexidine silver sulfadiazine-coated CVCs versus uncoated catheters, (5) well-fitted masks versus no mask, (6) amine fluoride-stannous fluoride versus sodium fluoride mouthwash, (7) low-bacterial diet versus standard hospital diet, and (8) herbal versus placebo mouthwash. No clear differences were reported in any of the outcomes examined in the first 3 comparisons. There were also no clear differences in the rate of catheter-related bloodstream infection or insertion site infection between the use of chlorhexidine silver sulfadiazine-coated CVCs versus uncoated catheters in the patients. Further, no significant differences were seen between patients who used a well-fitted mask and those without a mask in the incidence of OI. The all-cause mortality and mortality due to OI were similar between the 2 groups. There was no clear difference in all-cause mortality, although common adverse effects were reported in patients who used sodium fluoride mouthwash compared with those using amine fluoride-stannous fluoride mouthwash. There was no evidence of any difference in the incidence of possible invasive aspergillosis or candidemia between patients who consumed a low-bacterial diet and a standard diet. For the last comparison, no significant difference was seen between patients who received herbal and placebo mouthwash.
CONCLUSIONS: Very limited evidence was available to measure the effectiveness of nondrug interventions in hematological cancers. The effectiveness of the interventions included in this review needs to be evaluated further in high-quality RCTs in a dedicated setting among patients with hematological malignancies.
TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020169186; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=169186.
OBJECTIVE: To determine the efficacy of ivermectin in preventing progression to severe disease among high-risk patients with COVID-19.
DESIGN, SETTING, AND PARTICIPANTS: The Ivermectin Treatment Efficacy in COVID-19 High-Risk Patients (I-TECH) study was an open-label randomized clinical trial conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and October 25, 2021. Within the first week of patients' symptom onset, the study enrolled patients 50 years and older with laboratory-confirmed COVID-19, comorbidities, and mild to moderate disease.
INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive either oral ivermectin, 0.4 mg/kg body weight daily for 5 days, plus standard of care (n = 241) or standard of care alone (n = 249). The standard of care consisted of symptomatic therapy and monitoring for signs of early deterioration based on clinical findings, laboratory test results, and chest imaging.
MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who progressed to severe disease, defined as the hypoxic stage requiring supplemental oxygen to maintain pulse oximetry oxygen saturation of 95% or higher. Secondary outcomes of the trial included the rates of mechanical ventilation, intensive care unit admission, 28-day in-hospital mortality, and adverse events.
RESULTS: Among 490 patients included in the primary analysis (mean [SD] age, 62.5 [8.7] years; 267 women [54.5%]), 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk [RR], 1.25; 95% CI, 0.87-1.80; P = .25). For all prespecified secondary outcomes, there were no significant differences between groups. Mechanical ventilation occurred in 4 (1.7%) vs 10 (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17), intensive care unit admission in 6 (2.4%) vs 8 (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79), and 28-day in-hospital death in 3 (1.2%) vs 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09). The most common adverse event reported was diarrhea (14 [5.8%] in the ivermectin group and 4 [1.6%] in the control group).
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of high-risk patients with mild to moderate COVID-19, ivermectin treatment during early illness did not prevent progression to severe disease. The study findings do not support the use of ivermectin for patients with COVID-19.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04920942.
METHODS: Articles were included from a systematic search of Medline, Embase, Cochrane CENTRAL, ClinicalTrials.gov and International Clinical Trials Registry from inception to the 29th of August 2020.
RESULTS: There were 213 paediatric liver recipients who underwent PTA for PV stenosis in 19 included studies published between 1991 and 2019. Balloon angioplasty was the initial treatment in the majority (n = 153). Primary stent placement (n = 34) was performed for elastic recoil, intimal tears and PV kinks and rescue stent placement (n = 14) for recurrent PV stenosis following primary balloon angioplasty. The technical success was 97.6%-100% overall, 97.6%-100% for balloon-angioplasty-only and 100% for primary stenting. The clinical success was 50%-100% overall, 50%-100% for balloon-angioplasty-only and 100% for primary stenting. Long-term PV patency was 50%-100% overall, 37.5%-100% for balloon-angioplasty-only and 100% for primary stenting. Primary balloon angioplasty was successful in 78% of the cases. Of the recurrent PV stenoses, 9% resolved with stent placement and one required a meso-Rex shunt. There was one re-transplantation without stenting. The complication rate was 2.6% for balloon-angioplasty-only (bleeding, liver abscess, 2 PV thromboses) and 5.9% for primary stenting (bleeding, stent-fracture). There was no procedure-related mortality.
CONCLUSION: Percutaneous transhepatic balloon angioplasty may be the initial management of portal vein stenosis in paediatric liver recipients. Stent placement may be a primary option in selected cases and a reliable rescue option for recurrent portal vein stenosis following balloon-angioplasty-only.
METHODS AND ANALYSIS: We will identify observational studies through comprehensive literature searches. We will search: MEDLINE, Cochrane Central Register of Controlled Trials for published studies and trial registries including the WHO International Trial Registry Platform and ClinicalTrials.gov. Two reviewers will independently screen the titles and abstracts, attain full text of eligible articles, extract data, and appraise the quality and bias of the included studies. Disagreement among the authors will be resolved by discussion leading to a consensus. Next, we will perform a narrative synthesis of the study results. Study heterogeneity will be assessed using I2 statistics. If I2 is high (≥75%), and plausible heterogeneity contributors are found, we will divide the studies into appropriate subgroups for pooling of results or assess the association of plausible covariates and the prevalence estimates using meta-regression. If I2<75%, we will undertake meta-analysis using the random-effects model and transform all prevalence estimates using the Freeman-Tukey transformation for pooling, to obtain a synthesised point estimate of prevalence with its 95% confidence. We will then back-transform the point estimate, and report our results using the back-transformed figures.
ETHICS AND DISSEMINATION: Ethics approval is not a requirement as this study is based on available published data. Results of this systematic review will be presented at conferences, shared with relevant health authorities, and published in a peer-reviewed journal. These results may help quantify the magnitude of dyslipidaemia globally, and guide preventative and therapeutic interventions.
PROSPERO REGISTRATION NUMBER: CRD42020200281.
METHODS: This systematic review was conducted following Cochrane methodology and reported following the PRISMA guideline. Four databases (up to June 2021) were searched for RCTs comparing dance to standard or other physical therapy for improvements in disease severity, quality of life, cognitive and physical outcomes as well as adverse events in patients with PD. We synthesised data using RevMan and included certainty-of-evidence rating (GRADE) for major outcomes.
RESULTS: A total of 20 RCTs (N = 723) articles that evaluated Tango, Ballroom, Irish, Waltz-Foxtrot, Folk, Turo, mixed dances and a PD-tailored dance were included. Dancers (versus non-dancers) had better motor experience (MDS-UPDRS 3) (MD -6.01, 95 % CI -9.97 to -3.84; n = 148; 5 RCTs) and improved balance (MiniBest Test) (MD 4.47, 95 % CI 2.29 to 6.66; n = 95; 3 RCTs), with no consistent differences on gait, agility and cognitive outcomes. Small samples and methodological limitations resulted in low-certainty-evidence across outcomes.
CONCLUSIONS: Apart from a suggestion that dance intervention modestly reduced motor disease severity and improved certain aspects of balance, there is insufficient evidence on all other outcomes, such as agility and motor function, cognitive, mood and social outcomes, quality of life as well as adverse events including the risk of fall. As evidence is insufficient to inform practice, evidence of benefits on motor disease severity and balance needs to be considered in the context of user-perception of benefit versus harm and acceptability in the development of practice guideline recommendations.
OBJECTIVES: To assess the effectiveness and adverse effects of chloral hydrate as a sedative agent for non-invasive neurodiagnostic procedures in children.
SEARCH METHODS: We searched the following databases on 14 May 2020, with no language restrictions: the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 12 May 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy.
SELECTION CRITERIA: Randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo.
DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated studies identified by the search for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS: We included 16 studies with a total of 2922 children. The methodological quality of the included studies was mixed. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 16 studies were at high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in small studies. Fewer children who received oral chloral hydrate had sedation failure compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study; moderate-certainty evidence). More children who received oral chloral hydrate had sedation failure after one dose compared to intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study; low-certainty evidence), but there was no clear difference after two doses (RR 3.00, 95% CI 0.33 to 27.46; 1 study; very low-certainty evidence). Children with oral chloral hydrate had more sedation failure compared with rectal sodium thiopental (RR 1.33, 95% CI 0.60 to 2.96; 1 study; moderate-certainty evidence) and music therapy (RR 17.00, 95% CI 2.37 to 122.14; 1 study; very low-certainty evidence). Sedation failure rates were similar between groups for comparisons with oral dexmedetomidine, oral hydroxyzine hydrochloride, oral midazolam and oral clonidine. Children who received oral chloral hydrate had a shorter time to adequate sedation compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study) (moderate-certainty evidence for three aforementioned outcomes), rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study), and oral clonidine (MD -37.48, 95% CI -55.97 to -18.99; 1 study) (low-certainty evidence for two aforementioned outcomes). However, children with oral chloral hydrate took longer to achieve adequate sedation when compared with intravenous pentobarbital (MD 19, 95% CI 16.61 to 21.39; 1 study; low-certainty evidence), intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study; moderate-certainty evidence), and intranasal dexmedetomidine (MD 2.80, 95% CI 0.77 to 4.83; 1 study, moderate-certainty evidence). Children who received oral chloral hydrate appeared significantly less likely to complete neurodiagnostic procedure with child awakening when compared with rectal sodium thiopental (RR 0.95, 95% CI 0.83 to 1.09; 1 study; moderate-certainty evidence). Chloral hydrate was associated with a higher risk of the following adverse events: desaturation versus rectal sodium thiopental (RR 5.00, 95% 0.24 to 102.30; 1 study), unsteadiness versus intranasal dexmedetomidine (MD 10.21, 95% CI 0.58 to 178.52; 1 study), vomiting versus intranasal dexmedetomidine (MD 10.59, 95% CI 0.61 to 185.45; 1 study) (low-certainty evidence for aforementioned three outcomes), and crying during administration of sedation versus intranasal dexmedetomidine (MD 1.39, 95% CI 1.08 to 1.80; 1 study, moderate-certainty evidence). Chloral hydrate was associated with a lower risk of the following: diarrhoea compared with rectal sodium thiopental (RR 0.04, 95% CI 0.00 to 0.72; 1 study), lower mean diastolic blood pressure compared with sodium thiopental (MD 7.40, 95% CI 5.11 to 9.69; 1 study), drowsiness compared with oral clonidine (RR 0.44, 95% CI 0.30 to 0.64; 1 study), vertigo compared with oral clonidine (RR 0.15, 95% CI 0.01 to 2.79; 1 study) (moderate-certainty evidence for aforementioned four outcomes), and bradycardia compared with intranasal dexmedetomidine (MD 0.17, 95% CI 0.05 to 0.59; 1 study; high-certainty evidence). No other adverse events were significantly associated with chloral hydrate, although there was an increased risk of combined adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study; low-certainty evidence).
AUTHORS' CONCLUSIONS: The certainty of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine. Sedation failure was similar between groups for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. Oral chloral hydrate had a higher sedation failure rate when compared with intravenous pentobarbital, rectal sodium thiopental, and music therapy. Chloral hydrate appeared to be associated with higher rates of adverse events than intranasal dexmedetomidine. However, the evidence for the outcomes for oral chloral hydrate versus intravenous pentobarbital, rectal sodium thiopental, intranasal dexmedetomidine, and music therapy was mostly of low certainty, therefore the findings should be interpreted with caution. Further research should determine the effects of oral chloral hydrate on major clinical outcomes such as successful completion of procedures, requirements for an additional sedative agent, and degree of sedation measured using validated scales, which were rarely assessed in the studies included in this review. The safety profile of chloral hydrate should be studied further, especially for major adverse effects such as oxygen desaturation.
METHODS: Four attributes (ie, the scientific proof of effectiveness, the scientific proof of safety, the source of recommendation, and cost) were identified from a systematic review and focus group interviews. They were used to develop a DCE questionnaire. Consumers at community pharmacies in Malaysia were asked to respond to 8 DCE choice sets. A conditional logit model was employed to obtain the relative importance of each attribute and to estimate respondents' WTP for nutraceuticals.
RESULTS: A total of 111 valid responses were analyzed. A negative constant term in the developed model indicated that generally the respondents preferred not to use nutraceuticals before they considered the study attributes. The respondents preferred nutraceuticals with no side effect, clear evidence of effectiveness, and recommendation of a healthcare professional. The respondents were willing to pay $252/month more for nutraceuticals proven with no side effect than for those without proof of safety, and $102/month more for nutraceuticals proven with clear effectiveness than for those without proof of effectiveness.
CONCLUSIONS: Consumers weighed relatively high on the availability of safety and effectiveness proofs when they chose nutraceuticals. The study highlights on the crucial need to inform consumers using clinical evidences of nutraceuticals as the information is highly preferred by consumers.