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 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 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.
OBJECTIVES: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.
SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .
SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes. We evaluated the overall quality of the evidence supporting the outcomes assessed in this review using the GRADE criteria.
MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.We are very uncertain about the effects of TES on bowel movements, colonic transit, soiling symptoms and quality of life due to high risk of bias, indirectness and imprecision. For our outcomes of interest the 95% CI of most analysis results include potential benefit and no effect. There is insufficient evidence to determine the effect of TES on bowel movements and colonic transit. The study reported that 16/21 children in the TES group and 15/21 in the sham group had > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53; very low-quality evidence). Ten out of 14 children in the TES group had improved colonic transit compared to 1/7 in the sham group (RR 5.00, 95% CI 0.79 to 31.63; very low-quality evidence). Mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants; very low-quality evidence). The radiological assessment of colonic transit outcomes means that these results might not translate to important improvement in clinical symptoms or increased bowel movements. There is insufficient evidence to determine the effect of TES on symptoms and quality of life (QoL) outcomes. Nine out of 13 children in the TES group had improved soiling-related symptoms compared to 4/12 sham participants (RR 2.08, 95% CI 0.86 to 5.00; very low-quality evidence). Four out of 8 TES participants reported an improvement in QoL compared to 1/8 sham participants (RR 4.00, 95% CI 0.56 to 28.40; very low-quality evidence). The effects of TES on self-perceived (MD 5.00, 95% CI -1.21 to 11.21; one study, 33 participants; very low-quality evidence) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants; very low-quality evidence) are uncertain. No adverse effects were reported in the included study.
AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.
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 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: Our main objective was to evaluate the effectiveness and safety of TES when employed to improve bowel function and constipation-related symptoms in children with constipation.
SEARCH METHODS: We searched MEDLINE (PubMed) (1950 to July 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2015), EMBASE (1980 to July 2015), the Cochrane IBD Group Specialized Register, trial registries and conference proceedings to identify applicable studies .
SELECTION CRITERIA: Randomized controlled trials that assessed any type of TES, administered at home or in a clinical setting, compared to no treatment, a sham TES, other forms of nerve stimulation or any other pharmaceutical or non-pharmaceutical measures used to treat constipation in children were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion, extracted data and assessed risk of bias of the included studies. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for categorical outcomes data and the mean difference (MD) and corresponding 95% CI for continuous outcomes.
MAIN RESULTS: One study from Australia including 46 children aged 8 to 18 years was eligible for inclusion. There were multiple reports identified, including one unpublished report, that focused on different outcomes of the same study. The study had unclear risk of selection bias, high risks of performance, detection and attrition biases, and low risks of reporting biases.There were no significant differences between TES and the sham control group for the following outcomes: i).number of children with > 3 complete spontaneous bowel movements (CSBM) per week (RR 1.07, 95% CI 0.74 to 1.53, one study, 42 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision ), ii). number of children with improved colonic transit assessed radiologically (RR 5.00, 95% CI 0.79 to 31.63; one study, 21 participants) (Quality of evidence: very low, due to high risk of bias, serious imprecision and indirectness of the outcome). However, mean colonic transit rate, measured as the position of the geometric centre of the radioactive substance ingested along the intestinal tract, was significantly higher in children who received TES compared to sham (MD 1.05, 95% CI 0.36 to 1.74; one study, 30 participants) (Quality of evidence: very low, due to high risk of bias , serious imprecision and indirectness of the outcome). There was no significant difference between the two groups in the number of children with improved soiling-related symptoms (RR 2.08, 95% CI 0.86 to 5.00; one study, 25 participants) (Quality of evidence: very low, due to high risk of bias and serious imprecision). There was no significant difference in the number of children with improved quality of life (QoL) (RR 4.00, 95% CI 0.56 to 28.40; one study, 16 participants) (Quality of evidence: very low, due to high risk of bias issues and serious imprecision ). There were also no significant differences in in self-perceived (MD 5.00, 95% CI -1.21 to 11.21) or parent-perceived QoL (MD -0.20, 95% CI -7.57 to 7.17, one study, 33 participants for both outcomes) (Quality of evidence for both outcomes: very low, due to high risk of bias and serious imprecision). No adverse effects were reported in the included study.
AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the efficacy and safety of TES in children with chronic constipation can be drawn. Further randomized controlled trials assessing TES for the management of childhood constipation should be conducted. Future trials should include clear documentation of methodologies, especially measures to evaluate the effectiveness of blinding, and incorporate patient-important outcomes such as the number of patients with improved CSBM, improved clinical symptoms and quality of life.
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 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.
OBJECTIVES: To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
MAIN RESULTS: We included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years. There is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia. We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
AUTHORS' CONCLUSIONS: Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
OBJECTIVES: To assess the effects of interventions for treating different types of post-extraction bleeding.
SEARCH METHODS: We searched the following electronic databases: The Cochrane Oral Health Group Trials Register (to 22 March 2016); The Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2016, Issue 2); MEDLINE via OVID (1946 to 22 March 2016); CINAHL via EBSCO (1937 to 22 March 2016). Due to the ongoing Cochrane project to search EMBASE and add retrieved clinical trials to CENTRAL, we searched only the last 11 months of EMBASE via OVID (1 May 2015 to 22 March 2016). We placed no further restrictions on the language or date of publication. We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov), and the WHO Clinical Trials Registry Platform for ongoing trials (http://apps.who.int/trialsearch/default.aspx). We also checked the reference lists of excluded trials.
SELECTION CRITERIA: We considered randomised controlled trials (RCTs) that evaluated any intervention for treating PEB, with male or female participants of any age, regardless of type of teeth (anterior or posterior, mandibular or maxillary). Trials could compare one type of intervention with another, with placebo, or with no treatment.
DATA COLLECTION AND ANALYSIS: Three pairs of review authors independently screened search records. We obtained full papers for potentially relevant trials. If data had been extracted, we would have followed the methods described in the Cochrane Handbook for Systematic Reviews of Interventions for the statistical analysis.
MAIN RESULTS: We did not find any randomised controlled trial suitable for inclusion in this review.
AUTHORS' CONCLUSIONS: We were unable to identify any reports of randomised controlled trials that evaluated the effects of different interventions for the treatment of post-extraction bleeding. In view of the lack of reliable evidence on this topic, clinicians must use their clinical experience to determine the most appropriate means of treating this condition, depending on patient-related factors. There is a need for well designed and appropriately conducted clinical trials on this topic, which conform to the CONSORT statement (www.consort-statement.org/).
OBJECTIVES: To assess the effect of psychological interventions on psychological morbidities and quality of life among women with non-metastatic breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov up to 16 March 2021. We also scanned the reference lists of relevant articles.
SELECTION CRITERIA: Randomised controlled trials that assessed the effectiveness of psychological interventions for women with non-metastatic breast cancer.
DATA COLLECTION AND ANALYSIS: Two review authors independently appraised, extracted data from eligible trials, and assessed risk of bias and certainty of the evidence using the GRADE approach. Any disagreement was resolved by discussion. Extracted data included information about participants, methods, the intervention and outcomes.
MAIN RESULTS: We included 60 randomised controlled trials comprising 7998 participants. The most frequent reasons for exclusion were non-randomised trials and the inclusion of women with metastatic disease. The updated review included 7998 randomised women; the original review included 3940 women. A wide range of interventions was evaluated. Most interventions were cognitive- or mindfulness-based, supportive-expressive, and educational. The interventions were mainly delivered face-to-face (56 studies) and in groups (50 studies) rather than individually (10 studies). Most intervention sessions were delivered on a weekly basis with an average duration of 14 hours. Follow-up time ranged from two weeks to 24 months. Pooled standardised mean differences (SMD) from baseline indicated that the intervention may reduce depression (SMD -0.27, 95% confidence interval (CI) -0.52 to -0.02; P = 0.04; 27 studies, 3321 participants, I2 = 91%, low-certainty evidence); anxiety (SMD -0.43, 95% CI -0.68 to -0.17; P = 0.0009; 22 studies, 2702 participants, I2 = 89%, low-certainty evidence); mood disturbance in the intervention group (SMD -0.18, 95% CI -0.31 to -0.04; P = 0.009; 13 studies, 2276 participants, I2 = 56%, low-certainty evidence); and stress (SMD -0.34, 95% (CI) -0.55 to -0.12; P = 0.002; 8 studies, 564 participants, I2 = 31%, low-certainty evidence). The intervention is likely to improve quality of life in the intervention group (SMD 0.78, 95% (CI) 0.32 to 1.24; P = 0.0008; 20 studies, 1747 participants, I2 = 95%, low-certainty evidence). Adverse events were not reported in any of the included studies.
AUTHORS' CONCLUSIONS: Based on the available evidence, psychological intervention may have produced favourable effects on psychological outcomes, in particular depression, anxiety, mood disturbance and stress. There was also an improvement in quality of life in the psychological intervention group compared to control group. Overall, there was substantial variation across the studies in the range of psychological interventions used, control conditions, measures of the same outcome and timing of follow-up.
OBJECTIVES: The objective of this review is to assess the effects of lumbar sympathectomy by open, laparoscopic and percutaneous methods compared with no treatment or compared with any other method of lumbar sympathectomy in patients with CLI due to non-reconstructable PAD.
SEARCH METHODS: The Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (January 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 12). In addition, the CIS searched clinical trials databases for details of ongoing and unpublished studies.
SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any of the treatment modalities of lumbar sympathectomy, such as open, laparoscopic and chemical percutaneous methods, with no treatment or with any other method of lumbar sympathectomy for CLI due to non-reconstructable PAD were eligible. To decrease the bias of including participants that may be incorrectly diagnosed with CLI, review authors defined CLI as persistently recurring ischaemic rest pain requiring regular analgesia for more than two weeks, or ulceration or gangrene of the foot or toes, attributable to objectively proven arterial occlusive disease by measurement of ankle pressure of < 50 mmHg or toe pressure < 30 mmHg. We defined non-reconstructable PAD as a resting ankle brachial index (ABI) < 0.9 when no reasonable open surgical or endovascular revascularisation treatment option is available, as determined by individual trial vascular specialists.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies identified for potential inclusion in the review. We planned to conduct data collection and analysis in accordance with the Cochrane Handbook for Systematic Review of Interventions.
MAIN RESULTS: We identified no studies that met the predefined inclusion criteria. To decrease the bias of including participants who may be incorrectly diagnosed with CLI, we based our inclusion criteria on objective tests, as described above. The randomised trials identified by the literature search were performed before such objective criteria for selection were applied and therefore were not eligible for inclusion in the review.
AUTHORS' CONCLUSIONS: We identified no RCTs assessing effects of lumbar sympathectomy by open, laparoscopic and percutaneous methods compared with no treatment or compared with any other method of lumbar sympathectomy in patients with CLI due to non-reconstructable PAD. High-quality studies are needed.
OBJECTIVES: To assess the effects of pharmacological and non-pharmacological interventions for the management of gagging in people undergoing dental treatment.
SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the Cochrane Oral Health's Trials Register (to 18 March 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 2) in the Cochrane Library (searched 18 March 2019), MEDLINE Ovid (1946 to 18 March 2019), Embase Ovid (1980 to 18 March 2019), CINAHL EBSCO (1937 to 18 March 2019), AMED Ovid (1985 to 18 March 2019), and the proceedings of the International Association for Dental Research (IADR) online (2001 to 18 March 2019). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. We also conducted forwards citation searching on the included studies via Google Scholar. No restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA: We included randomised controlled trials (RCTs), involving people who were given a pharmacological or non-pharmacological intervention to manage gagging that interfered with dental treatment. We excluded quasi-RCTs. We excluded trials with participants who had central or peripheral nervous system disorders, who had oral lesions or were on systemic medications that might affect the gag sensation, or had undergone surgery which might alter anatomy permanently.
DATA COLLECTION AND ANALYSIS: We independently selected trials, extracted data, and assessed risk of bias. We followed Cochrane's statistical guidelines. We assessed the overall certainty of the evidence using GRADE.
MAIN RESULTS: We included four trials at unclear risk of bias with 328 participants (263 adults and 65 children who were four years or older), in which one trial compared acupuncture and acupressure (with thumb, device and sea band) at P6 (point located three-finger breadths below the wrist on the inner forearm in between the two tendons) to sham acupuncture and acupressure with and without sedation. One trial compared acupuncture at P6 point to sham acupuncture. These trials reported both completion of dental procedure and reduction in gagging (assessor and patient reported) as their outcomes. One cross-over and one split-mouth trial studied the effect of laser at P6 point compared to control. One trial reported reduction in gagging and another reported presence or absence of gagging during dental procedure. Acupuncture at P6 showed uncertain evidence regarding the successful completion of dental procedure (RR 1.78, 95% CI 1.05 to 3.01; two trials, 59 participants; very low-certainty evidence) and uncertain evidence regarding the reduction in gagging (RR 2.57, 95% CI 1.12 to 5.89; one trial, 26 participants; very low-certainty evidence) in comparison to sham acupuncture. Acupuncture at P6 with sedation did not show any difference when compared to sham acupuncture with sedation (RR 1.08, 95% CI 0.91 to 1.28; one trial, 34 participants; very low-certainty evidence). Acupressure using thumb pressure with or without sedation showed no clear difference in completing dental procedure (RR 0.96, 95% CI 0.84 to 1.10; one trial, 39 participants; very low-certainty evidence; and RR 0.85, 95% CI 0.50 to 1.46; one trial, 30 participants; very low-certainty evidence; respectively), or reduction in gagging (RR 1.06, 95% CI 0.92 to 1.23; one trial, 39 participants; very low-certainty evidence; and RR 0.92, 95% CI 0.60 to 1.41; one trial, 30 participants; very low-certainty evidence; respectively) when compared to sham acupressure with or without sedation. Acupressure at P6 with device showed uncertain evidence regarding the successful completion of dental procedure (RR 2.63, 95% CI 1.33 to 5.18; one trial, 34 participants; very low-certainty evidence) and uncertain evidence regarding the reduction in gagging (RR 3.94, 95% CI 1.63 to 9.53; one trial, 34 participants; very low-certainty evidence) when compared to sham acupressure. However, device combined with sedation showed no difference for either outcome (RR 1.16, 95% CI 0.90 to 1.48; one trial, 27 participants; very low-certainty evidence; and RR 1.26, 95% CI 0.93 to 1.69; one trial, 27 participants; very low-certainty evidence; respectively). Acupressure using a sea band with or without sedation showed no clear difference in completing dental procedure (RR 0.88, 95% CI 0.67 to 1.17; one trial, 21 participants; very low-certainty evidence; and RR 1.80, 95% CI 0.63 to 5.16; one trial, 19 participants; very low-certainty evidence; respectively), or reduction in gagging (RR 0.88, 95% CI 0.67 to 1.17; one trial, 21 participants; very low-certainty evidence; and RR 2.70, 95% CI 0.72 to 10.14; one trial, 19 participants; very low-certainty evidence; respectively) when compared to sham acupressure with or without sedation. Laser at P6 showed a difference in absence of gagging (odds ratio (OR) 86.33, 95% CI 29.41 to 253.45; one trial, 40 participants; very low-certainty evidence) and reduction in gagging (MD 1.80, 95% CI 1.53 to 2.07; one trial, 25 participants; very low-certainty evidence) during dental procedure when compared to dummy laser application. No noteworthy adverse effects were reported. For acupuncture at P6, the trial authors were unsure whether the reported adverse effects were due to participant anxiety or due to the intervention. None of the trials on acupressure or laser reported on this outcome. We did not find trials evaluating any other interventions used to manage gagging in people undergoing dental treatment.
AUTHORS' CONCLUSIONS: We found very low-certainty evidence from four trials that was insufficient to conclude if there is any benefit of acupuncture, acupressure or laser at P6 point in reducing gagging and allowing successful completion of dental procedures. We did not find any evidence on any other interventions for managing the gag reflex during dental treatment. More well-designed and well-reported trials evaluating different interventions are needed.
OBJECTIVES: To assess methods of treating dental complications in people with sickle cell disease.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Review Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 01 August 2019. Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field. Date of last search: 07 November 2019.
SELECTION CRITERIA: We searched for published or unpublished randomised controlled studies of treatments for dental complications in people with sickle cell disease.
DATA COLLECTION AND ANALYSIS: Two review authors intended to independently extract data and assess the risk of bias of the included studies using standard Cochrane methodologies; however, no studies were identified for inclusion in the review.
MAIN RESULTS: No randomised controlled studies were identified.
AUTHORS' CONCLUSIONS: This Cochrane Review did not identify any randomised controlled studies assessing interventions for the treatment of dental complications in people with sickle cell disease. There is an important need for randomised controlled studies in this area, so as to identify the most effective and safe method for treating dental complications in people with sickle cell disease.
OBJECTIVES: The objective of this review is to compare the effects of different medical interventions in people diagnosed with cystic fibrosis and chronic rhinosinusitis.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. Date of last search of trials register: 09 September 2021. We also searched ongoing trials databases, other medical databases and the reference lists of relevant articles and reviews. Date of latest additional searches: 22 November 2021.
SELECTION CRITERIA: Randomized and quasi-randomized trials of different medical interventions compared to each other or to no intervention or to placebo.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials identified for potential inclusion in the review. We planned to conduct data collection and analysis in accordance with Cochrane methods and to independently rate the quality of the evidence for each outcome using the GRADE guidelines.
MAIN RESULTS: We identified no trials that met the pre-defined inclusion criteria. The most recent searches identified 44 new references, none of which were eligible for inclusion in the current version of this review; 12 studies are listed as excluded and one as ongoing.
AUTHORS' CONCLUSIONS: We identified no eligible trials assessing the medical interventions in people with cystic fibrosis and chronic rhinosinusitis. High-quality trials are needed which should assess the efficacy of different treatment options detailed above for managing chronic rhinosinusitis, preventing pulmonary exacerbations and improving quality of life in people with cystic fibrosis.
OBJECTIVES: This review aimed to examine the benefits and harms of human albumin infusion for treating oedema associated with nephrotic syndrome.
SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 23 June 2019 through contact with the Information Specialists using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of human albumin infusion compared with placebo or no intervention, human albumin with diuretics compared with diuretic alone, human albumin compared with diuretics and other treatments, clinical outcomes, death, quality of life, kidney function and adverse effects in people with nephrotic syndrome. We excluded cross-over studies but data for the first period was to be included if available.
DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration were used. Two authors independently assessed eligibility, risk of bias, study quality and extracted data. We calculated mean difference (MD) for continuous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE.
MAIN RESULTS: One study met our inclusion criteria (26 children with minimal change nephrotic syndrome) and 11 were excluded (nine cross-over studies, one where albumin was not used for nephrotic syndrome and one where authors did not state whether the children had oedema). Risk of bias for the included study was unclear for selection bias, high for performance and detection bias, low for attrition bias, and high for selective reporting. The included study compared albumin plus furosemide with an equal volume of dextrose. Of our prespecified outcomes, the authors reported clinical improvement as weight change, serum sodium and adverse outcomes (blood pressure). The authors reported a greater weight loss in the albumin treated group initially but no difference overall at 10 days. However, the data in the text and the figures were inconsistent so we could not confirm the authors statements (very low certainty evidence). It is uncertain whether albumin infusion improves serum sodium when compared with an equal volume of dextrose (MD 2.00 mEq/L, 95% CI -0.09 to 4.09), systolic blood pressure (MD 2.00 mmHg, 95% CI -3.52 to 7.52) or diastolic blood pressure (MD 2.00 mmHg, 95%CI -4.29 to 8.29). Death, quality of life, and kidney function were not reported.
AUTHORS' CONCLUSIONS: We identified only one small study that was relevant to our review, therefore we are unable to draw any conclusions regarding the use of human albumin with or without diuretics in nephrotic syndrome. More RCTs are needed.
OBJECTIVES: To evaluate all randomized controlled trials (RCTs) that have assessed strategies for treatment and prevention of heavy menstrual bleeding or pain associated with IUD use, for example, pharmacotherapy and alternative therapies.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and CINAHL to January 2021.
SELECTION CRITERIA: We included RCTs in any language that tested strategies for treatment or prevention of heavy menstrual bleeding or pain associated with IUD (Cu IUD, LNG IUD or other IUD) use. The comparison could be no intervention, placebo or another active intervention.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, and extracted data. Primary outcomes were volume of menstrual blood loss, duration of menstruation and painful menstruation. We used a random-effects model in all meta-analyses. Review authors assessed the certainty of evidence using GRADE.
MAIN RESULTS: This review includes 21 trials involving 3689 participants from middle- and high-income countries. Women were 18 to 45 years old and either already using an IUD or had just had one placed for contraception. The included trials examined NSAIDs and other interventions. Eleven were treatment trials, of these seven were on users of the Cu IUD, one on LNG IUD and three on an unknown type. Ten were prevention trials, six focused on Cu IUD users, and four on LNG IUD users. Sixteen trials had high risk of detection bias due to subjective assessment of pain and bleeding. Treatment of heavy menstrual bleeding Cu IUD Vitamin B1 resulted in fewer pads used per day (mean difference (MD) -7.00, 95% confidence interval (CI) -8.50 to -5.50) and fewer bleeding days (MD -2.00, 95% CI -2.38 to -1.62; 1 trial; 110 women; low-certainty evidence) compared to placebo. The evidence is very uncertain about the effect of naproxen on the volume of menstruation compared to placebo (odds ratio (OR) 0.09, 95% CI 0.00 to 1.78; 1 trial, 40 women; very low-certainty evidence). Treatment with mefenamic acid resulted in less volume of blood loss compared to tranexamic acid (MD -64.26, 95% CI -105.65 to -22.87; 1 trial, 94 women; low-certainty evidence). However, there was no difference in duration of bleeding with treatment of mefenamic acid or tranexamic acid (MD 0.08 days, 95% CI -0.27 to 0.42, 2 trials, 152 women; low-certainty evidence). LNG IUD The use of ulipristal acetate in LNG IUD may not reduce the number of bleeding days in 90 days in comparison to placebo (MD -9.30 days, 95% CI -26.76 to 8.16; 1 trial, 24 women; low-certainty evidence). Unknown IUD type Mefenamic acid may not reduce volume of bleeding compared to Vitex agnus measured by pictorial blood assessment chart (MD -2.40, 95% CI -13.77 to 8.97; 1 trial; 84 women; low-certainty evidence). Treatment of pain Cu IUD Treatment with tranexamic acid and sodium diclofenac may result in little or no difference in the occurrence of pain (OR 1.00, 95% CI 0.06 to 17.25; 1 trial, 38 women; very low-certainty evidence). Unknown IUD type Naproxen may reduce pain (MD 4.10, 95% CI 0.91 to 7.29; 1 trial, 33 women; low-certainty evidence). Prevention of heavy menstrual bleeding Cu IUD We found very low-certainty evidence that tolfenamic acid may prevent heavy bleeding compared to placebo (OR 0.54, 95% CI 0.34 to 0.85; 1 trial, 310 women). There was no difference between ibuprofen and placebo in blood volume reduction (MD -14.11, 95% CI -36.04 to 7.82) and duration of bleeding (MD -0.2 days, 95% CI -1.40 to 1.0; 1 trial, 28 women, low-certainty evidence). Aspirin may not prevent heavy bleeding in comparison to paracetamol (MD -0.30, 95% CI -26.16 to 25.56; 1 trial, 20 women; very low-certainty evidence). LNG IUD Ulipristal acetate may increase the percentage of bleeding days compared to placebo (MD 9.50, 95% CI 1.48 to 17.52; 1 trial, 118 women; low-certainty evidence). There were insufficient data for analysis in a single trial comparing mifepristone and vitamin B. There were insufficient data for analysis in the single trial comparing tranexamic acid and mefenamic acid and in another trial comparing naproxen with estradiol. Prevention of pain Cu IUD There was low-certainty evidence that tolfenamic acid may not be effective to prevent painful menstruation compared to placebo (OR 0.71, 95% CI 0.44 to 1.14; 1 trial, 310 women). Ibuprofen may not reduce menstrual cramps compared to placebo (OR 1.00, 95% CI 0.11 to 8.95; 1 trial, 20 women, low-certainty evidence).
AUTHORS' CONCLUSIONS: Findings from this review should be interpreted with caution due to low- and very low-certainty evidence. Included trials were limited; the majority of the evidence was derived from single trials with few participants. Further research requires larger trials and improved trial reporting. The use of vitamin B1 and mefenamic acid to treat heavy menstruation and tolfenamic acid to prevent heavy menstruation associated with Cu IUD should be investigated. More trials are needed to generate evidence for the treatment and prevention of heavy and painful menstruation associated with LNG IUD.
OBJECTIVES: To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events.
SEARCH METHODS: We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings.
SELECTION CRITERIA: Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded.
DATA COLLECTION AND ANALYSIS: Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach.
MAIN RESULTS: Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%)Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%)Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence).The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%)Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence).Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium species In studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax.
AUTHORS' CONCLUSIONS: MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings.To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance.