OBJECTIVES: To compare the efficacy and safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients.
SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Allied and Complementary Medicine Database (AMED), and trials registries (16 May 2018). Review authors searched PubMed until February 2017.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving 'no-option' CLI patients comparing a particular source or regimen of autologous cell-based therapy against another source or regimen of autologous cell-based therapy.
DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the eligibility and methodological quality of the trials. We extracted outcome data from each trial and pooled them for meta-analysis. We calculated effect estimates using a risk ratio (RR) with 95% confidence interval (CI), or a mean difference (MD) with 95% CI.
MAIN RESULTS: We included seven RCTs with a total of 359 participants. These studies compared bone marrow-mononuclear cells (BM-MNCs) versus mobilised peripheral blood stem cells (mPBSCs), BM-MNCs versus bone marrow-mesenchymal stem cells (BM-MSCs), high cell dose versus low cell dose, and intramuscular (IM) versus intra-arterial (IA) routes of cell implantation. We identified no other comparisons in these studies. We considered most studies to be at low risk of bias in random sequence generation, incomplete outcome data, and selective outcome reporting; at high risk of bias in blinding of patients and personnel; and at unclear risk of bias in allocation concealment and blinding of outcome assessors. The quality of evidence was most often low to very low, with risk of bias, imprecision, and indirectness of outcomes the major downgrading factors.Three RCTs (100 participants) reported a total of nine deaths during the study follow-up period. These studies did not report deaths according to treatment group.Results show no clear difference in amputation rates between IM and IA routes (RR 0.80, 95% CI 0.54 to 1.18; three RCTs, 95 participants; low-quality evidence). Single-study data show no clear difference in amputation rates between BM-MNC- and mPBSC-treated groups (RR 1.54, 95% CI 0.45 to 5.24; 150 participants; low-quality evidence) and between high and low cell dose (RR 3.21, 95% CI 0.87 to 11.90; 16 participants; very low-quality evidence). The study comparing BM-MNCs versus BM-MSCs reported no amputations.Single-study data with low-quality evidence show similar numbers of participants with healing ulcers between BM-MNCs and mPBSCs (RR 0.89, 95% CI 0.44 to 1.83; 49 participants) and between IM and IA routes (RR 1.13, 95% CI 0.73 to 1.76; 41 participants). In contrast, more participants appeared to have healing ulcers in the BM-MSC group than in the BM-MNC group (RR 2.00, 95% CI 1.02 to 3.92; one RCT, 22 participants; moderate-quality evidence). Researchers comparing high versus low cell doses did not report ulcer healing.Single-study data show similar numbers of participants with reduction in rest pain between BM-MNCs and mPBSCs (RR 0.99, 95% CI 0.93 to 1.06; 104 participants; moderate-quality evidence) and between IM and IA routes (RR 1.22, 95% CI 0.91 to 1.64; 32 participants; low-quality evidence). One study reported no clear difference in rest pain scores between BM-MNC and BM-MSC (MD 0.00, 95% CI -0.61 to 0.61; 37 participants; moderate-quality evidence). Trials comparing high versus low cell doses did not report rest pain.Single-study data show no clear difference in the number of participants with increased ankle-brachial index (ABI; increase of > 0.1 from pretreatment), between BM-MNCs and mPBSCs (RR 1.00, 95% CI 0.71 to 1.40; 104 participants; moderate-quality evidence), and between IM and IA routes (RR 0.93, 95% CI 0.43 to 2.00; 35 participants; very low-quality evidence). In contrast, ABI scores appeared higher in BM-MSC versus BM-MNC groups (MD 0.05, 95% CI 0.01 to 0.09; one RCT, 37 participants; low-quality evidence). ABI was not reported in the high versus low cell dose comparison.Similar numbers of participants had improved transcutaneous oxygen tension (TcO₂) with IM versus IA routes (RR 1.22, 95% CI 0.86 to 1.72; two RCTs, 62 participants; very low-quality evidence). Single-study data with low-quality evidence show a higher TcO₂ reading in BM-MSC versus BM-MNC groups (MD 8.00, 95% CI 3.46 to 12.54; 37 participants) and in mPBSC- versus BM-MNC-treated groups (MD 1.70, 95% CI 0.41 to 2.99; 150 participants). TcO₂ was not reported in the high versus low cell dose comparison.Study authors reported no significant short-term adverse effects attributed to autologous cell implantation.
AUTHORS' CONCLUSIONS: Mostly low- and very low-quality evidence suggests no clear differences between different stem cell sources and different treatment regimens of autologous cell implantation for outcomes such as all-cause mortality, amputation rate, ulcer healing, and rest pain for 'no-option' CLI patients. Pooled analyses did not show a clear difference in clinical outcomes whether cells were administered via IM or IA routes. High-quality evidence is lacking; therefore the efficacy and long-term safety of autologous cells derived from different sources, prepared using different protocols, administered at different doses, and delivered via different routes for the treatment of 'no-option' CLI patients, remain to be confirmed.Future RCTs with larger numbers of participants are needed to determine the efficacy of cell-based therapy for CLI patients, along with the optimal cell source, phenotype, dose, and route of implantation. Longer follow-up is needed to confirm the durability of angiogenic potential and the long-term safety of cell-based therapy.
OBJECTIVES: To assess the effects of cell-based therapy for people with ALS/MND, compared with placebo or no treatment.
SEARCH METHODS: On 31 July 2019, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched two clinical trials registries for ongoing or unpublished studies.
SELECTION CRITERIA: We included RCTs that assigned people with ALS/MND to receive cell-based therapy versus a placebo or no additional treatment. Co-interventions were allowed, provided that they were given to each group equally.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology.
MAIN RESULTS: Two RCTs involving 112 participants were eligible for inclusion in this review. One study compared autologous bone marrow-mesenchymal stem cells (BM-MSC) plus riluzole versus control (riluzole only), while the other study compared combined intramuscular and intrathecal administration of autologous mesenchymal stem cells secreting neurotrophic factors (MSC-NTF) to placebo. The latter study was reported as an abstract and provided no numerical data. Both studies were funded by biotechnology companies. The only study that contributed to the outcome data in the review involved 64 participants, comparing BM-MSC plus riluzole versus control (riluzole only). It reported outcomes after four to six months. It had a low risk of selection bias, detection bias and reporting bias, but a high risk of performance bias and attrition bias. The certainty of evidence was low for all major efficacy outcomes, with imprecision as the main downgrading factor, because the range of plausible estimates, as shown by the 95% confidence intervals (CIs), encompassed a range that would likely result in different clinical decisions. Functional impairment, expressed as the mean change in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score from baseline to six months after cell injection was slightly reduced (better) in the BM-MSC group compared to the control group (mean difference (MD) 3.38, 95% CI 1.22 to 5.54; 1 RCT, 56 participants; low-certainty evidence). ALSFRS-R has a range from 48 (normal) to 0 (maximally impaired); a change of 4 or more points is considered clinically important. The trial did not report outcomes at 12 months. There was no clear difference between the BM-MSC and the no treatment group in change in respiratory function (per cent predicted forced vital capacity; FVC%; MD -0.53, 95% CI -5.37 to 4.31; 1 RCT, 56 participants; low-certainty evidence); overall survival at six months (risk ratio (RR) 1.07, 95% CI 0.94 to 1.22; 1 RCT, 64 participants; low-certainty evidence); risk of total adverse events (RR 0.86, 95% CI 0.62 to 1.19; 1 RCT, 64 participants; low-certainty evidence) or serious adverse events (RR 0.47, 95% CI 0.13 to 1.72; 1 RCT, 64 participants; low-certainty evidence). The study did not measure muscle strength.
AUTHORS' CONCLUSIONS: Currently, there is a lack of high-certainty evidence to guide practice on the use of cell-based therapy to treat ALS/MND. Uncertainties remain as to whether this mode of therapy is capable of restoring muscle function, slowing disease progression, and improving survival in people with ALS/MND. Although one RCT provided low-certainty evidence that BM-MSC may slightly reduce functional impairment measured on the ALSFRS-R after four to six months, this was a small phase II trial that cannot be used to establish efficacy. We need large, prospective RCTs with long-term follow-up to establish the efficacy and safety of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research are to determine the appropriate cell source, phenotype, dose and method of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.
OBJECTIVES: To assess the effects of cell-based therapy for people with ALS/MND, compared with placebo or no additional treatment.
SEARCH METHODS: On 21 June 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched two clinical trials' registries for ongoing or unpublished studies.
SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs), quasi-RCTs and cluster RCTs that assigned people with ALS/MND to receive cell-based therapy versus a placebo or no additional treatment. Co-interventions were allowable, provided that they were given to each group equally.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology.
MAIN RESULTS: No studies were eligible for inclusion in the review. We identified four ongoing trials.
AUTHORS' CONCLUSIONS: Currently, there is a lack of high-quality evidence to guide practice on the use of cell-based therapy to treat ALS/MND.We need large, prospective RCTs to establish the efficacy of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research should be to determine the appropriate cell source, phenotype, dose, and route of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.
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.
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.
Methods: We searched 4 electronic databases (Medline, the Cochrane Central Register of Controlled Trials, Embase, CINAHL) and internet sources for randomized controlled trials, ongoing clinical trials, and unpublished studies up to August 2016. Studies that assessed CVCs with antimicrobial impregnation with nonimpregnated catheters or catheters with another impregnation were included. Primary outcomes were clinically diagnosed sepsis, catheter-related bloodstream infection (CRBSI), and all-cause mortality. We performed a network meta-analysis to estimate risk ratio (RR) with 95% confidence interval (CI).
Results: Sixty studies with 17255 catheters were included. The effects of 14 impregnations were investigated. Both CRBSI and catheter colonization were the most commonly evaluated outcomes. Silver-impregnated CVCs significantly reduced clinically diagnosed sepsis compared with silver-impregnated cuffs (RR, 0.54 [95% CI, .29-.99]). When compared to no impregnation, significant CRBSI reduction was associated with minocycline-rifampicin (RR, 0.29 [95% CI, .16-.52]) and silver (RR, 0.57 [95% CI, .38-.86]) impregnations. No impregnations significantly reduced all-cause mortality. For catheter colonization, significant decreases were shown by miconazole-rifampicin (RR, 0.14 [95% CI, .05-.36]), 5-fluorouracil (RR, 0.34 [95% CI, .14-.82]), and chlorhexidine-silver sulfadiazine (RR, 0.60 [95% CI, .50-.72]) impregnations compared with no impregnation. None of the studies evaluated antibiotic/antiseptic resistance as the outcome.
Conclusions: Current evidence suggests that the minocycline-rifampicin-impregnated CVC appears to be the most effective in preventing CRBSI. However, its overall benefits in reducing clinical sepsis and mortality remain uncertain. Surveillance for antibiotic resistance attributed to the routine use of antimicrobial-impregnated CVCs should be emphasized in future trials.
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.
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 used the standard search strategy of the Cochrane Epilepsy Group. We searched MEDLINE (OVID SP) (1950 to July 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 7, 2017), Embase (1980 to July 2017), and the Cochrane Epilepsy Group Specialized Register (via CENTRAL) using a combination of keywords and MeSH headings.
SELECTION CRITERIA: We included randomised controlled trials that assessed chloral hydrate agent against other sedative agent(s), non-drug agent(s), or placebo for children undergoing non-invasive neurodiagnostic procedures.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for their eligibility, extracted data, and assessed risk of bias. Results were expressed in terms of risk ratio (RR) for dichotomous data, mean difference (MD) for continuous data, with 95% confidence intervals (CIs).
MAIN RESULTS: We included 13 studies with a total of 2390 children. The studies were all conducted in hospitals that provided neurodiagnostic services. Most studies assessed the proportion of sedation failure during the neurodiagnostic procedure, time for adequate sedation, and potential adverse effects associated with the sedative agent.The methodological quality of the included studies was mixed, as reflected by a wide variation in their 'Risk of bias' profiles. Blinding of the participants and personnel was not achieved in most of the included studies, and three of the 13 studies had high risk of bias for selective reporting. Evaluation of the efficacy of the sedative agents was also underpowered, with all the comparisons performed in single small studies.Children who received oral chloral hydrate had lower sedation failure when compared with oral promethazine (RR 0.11, 95% CI 0.01 to 0.82; 1 study, moderate-quality evidence). Children who received oral chloral hydrate had a higher risk of sedation failure after one dose compared to those who received intravenous pentobarbital (RR 4.33, 95% CI 1.35 to 13.89; 1 study, low-quality evidence), but after two doses there was no evidence of a significant difference between the two groups (RR 3.00, 95% CI 0.33 to 27.46; 1 study, very low-quality evidence). Children who received oral chloral hydrate appeared to have more sedation failure when compared with music therapy, but the quality of evidence was very low for this outcome (RR 17.00, 95% CI 2.37 to 122.14; 1 study). Sedation failure rates were similar between oral chloral hydrate, oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam.Children who received oral chloral hydrate had a shorter time to achieve adequate sedation when compared with those who received oral dexmedetomidine (MD -3.86, 95% CI -5.12 to -2.6; 1 study, moderate-quality evidence), oral hydroxyzine hydrochloride (MD -7.5, 95% CI -7.85 to -7.15; 1 study, moderate-quality evidence), oral promethazine (MD -12.11, 95% CI -18.48 to -5.74; 1 study, moderate-quality evidence), and rectal midazolam (MD -95.70, 95% CI -114.51 to -76.89; 1 study). 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-quality evidence) and intranasal midazolam (MD 12.83, 95% CI 7.22 to 18.44; 1 study, moderate-quality evidence).No data were available to assess the proportion of children with successful completion of neurodiagnostic procedure without interruption by the child awakening. Most trials did not assess adequate sedation as measured by specific validated scales, except in the comparison of chloral hydrate versus intranasal midazolam and oral promethazine.Compared to dexmedetomidine, chloral hydrate was associated with a higher risk of nausea and vomiting (RR 12.04 95% CI 1.58 to 91.96). No other adverse events were significantly associated with chloral hydrate (including behavioural change, oxygen desaturation) although there was an increased risk of adverse events overall (RR 7.66, 95% CI 1.78 to 32.91; 1 study, low-quality evidence).
AUTHORS' CONCLUSIONS: The quality of evidence for the comparisons of oral chloral hydrate against several other methods of sedation was very variable. Oral chloral hydrate appears to have a lower sedation failure rate when compared with oral promethazine for children undergoing paediatric neurodiagnostic procedures. The sedation failure was similar for other comparisons such as oral dexmedetomidine, oral hydroxyzine hydrochloride, and oral midazolam. When compared with intravenous pentobarbital and music therapy, oral chloral hydrate had a higher sedation failure rate. However, it must be noted that the evidence for the outcomes for the comparisons of oral chloral hydrate against intravenous pentobarbital and music therapy was of very low to low quality, therefore the corresponding 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 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 the risk of major adverse effects such as bradycardia, hypotension, and oxygen desaturation.
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.
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.