OBJECTIVES: To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 November 2019. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 01 January 2020.
SELECTION CRITERIA: Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both).
DATA COLLECTION AND ANALYSIS: Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review.
MAIN RESULTS: A comprehensive search of the literature did not identify any published eligible randomised controlled trials.
AUTHORS' CONCLUSIONS: In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.
METHODS: This scoping review was reported based on Preferred Reporting Items for Systematic reviews and Meta-Analyses-extension for Scoping Reviews guidelines. A systematic search identified records from 4 databases: PubMed, Embase, Cochrane Library, and Web of Science. Abstracts received 3 blind reviews. Corresponding full-text articles rated as "in-scope" and reporting data not published in any other retained article (i.e., no double reporting) were identified and assigned to 5 thematic evaluating teams. Full-text articles were reviewed using a double-blind standardized form. Level of evidence was graded, and summative statements were generated.
RESULTS: On November 9, 2022, 2,167 documents had been identified; 132 articles were retained, of which 33 (25%) were published over the past 5 years. Overall, 2,161 individuals met the inclusion criteria; female patients were 527 of 1,554 (33.9%) cases included, whose sex was identifiable. Of 132 articles, 57 (43.2%) were single case reports and only 5 (3.8%) clinical trials; the level of evidence was prevalently low (80/132; 60.6%). Most studies included neurobehavioral measures (84/127; 66.1%) and neuroimaging (81/127; 63.8%); 59 (46.5%) were mainly related to diagnosis, 56 (44.1%) to prognosis, and 44 (34.6%) to treatment. Most frequently used neurobehavioral tools included the Coma Recovery Scale-Revised, Coma/Near-Coma Scale, Level of Cognitive Functioning Assessment Scale, and Post-Acute Level of Consciousness scale. EEG, event-related potentials, structural CT, and MRI were the most frequently used instrumental techniques. In 29/53 (54.7%) cases, DoC improvement was observed, which was associated with treatment with amantadine.
DISCUSSION: The literature on pediatric DoCs is mainly observational, and clinical details are either inconsistently presented or absent. Conclusions drawn from many studies convey insubstantial evidence and have limited validity and low potential for translation in clinical practice. Despite these limitations, our work summarizes the extant literature and constitutes a base for future guidelines related to the diagnosis, prognosis, and treatment of pediatric DoC.
METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, MEDLINE, China National Knowledge Infrastructure (CNKI) and Wanfang Database were searched for relevant randomized controlled trials up to March 2016. Two review authors independently selected trials for inclusion, extracted data, assessed the methodological quality and rated the quality of evidence with the Grading of Recommendations, Assessment, Development and Evaluation approach.
RESULTS: Twelve studies involving 655 participants were included. Evidence of low to moderate-quality showed that cordyceps plus conventional treatment compared to conventional treatment alone significantly improved C-reactive protein [standardized mean difference (SMD) －0.61; 95% confidence intervals (CI) －1.00 to －0.22], high-sensitivity C-reactive protein [weighted mean difference (WMD) －3.44 mg/L; 95% CI －3.89 to －2.99], serum albumin (WMD 3.07 g/L; 95% CI 1.59 to 4.55), malondialdehyde (WMD －1.95 nmol/L; 95% CI －2.24 to －1.66), and hemoglobin (WMD 9.56 g/L; 95% CI 3.65 to 15.47) levels. However, there was no significant improvement for serum creatinine and low-density lipoprotein cholesterol. Overall, most trials either did not monitor adverse events or poorly documented them.
CONCLUSION: Given the small number of trials included, the unclear methodological quality of the included trials, and the high heterogeneity in pooled analyses, the evidence obtained in this review is insufficient to recommend the use of cordyceps as adjunctive treatment in hemodialysis patients.
METHODS: Online literature search databases including Scopus, Web of Science, PubMed/Medline, Embase and Google Scholar were searched to discover relevant articles available up to 17 March 2020. We used mean changes and SD of the outcomes to assess treatment response from baseline and mean difference, and 95 % CI were calculated to combined data and assessment effect sizes in astaxanthin and control groups.
RESULTS: 14 eligible articles were included in the final quantitative analysis. Current study revealed that astaxanthin consumption was not associated with FBS, HbA1c, TC, LDL-C, TG, BMI, BW, DBP, and SBP. We did observe an overall increase in HDL-C (WMD: 1.473 mg/dl, 95 % CI: 0.319-2.627, p = 0.012). As for the levels of CRP, only when astaxanthin was administered (i) for relatively long periods (≥ 12 weeks) (WMD: -0.528 mg/l, 95 % CI: -0.990 to -0.066), and (ii) at high dose (> 12 mg/day) (WMD: -0.389 mg/dl, 95 % CI: -0.596 to -0.183), the levels of CRP would decrease.
CONCLUSION: In summary, our systematic review and meta-analysis revealed that astaxanthin consumption was associated with increase in HDL-C and decrease in CRP. Significant associations were not observed for other outcomes.
METHODS AND RESULTS: A systematic review and dose-response meta-analysis of randomized controlled trials (RCTs) was performed employing in Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar, then including relevant articles that addressed the effects of DHEA supplementation on the lipid profile, up to February 2020. Combined findings were generated from 23 eligible articles. Hence, total cholesterol (TC) (weighted mean difference (WMD): -3.5 mg/dl, 95% confidence interval (CI): -8.5 to 1.6)), low-density lipoprotein-cholesterol (LDL-C) (WMD: 0.34 mg/dl, 95% CI: -3 to 3.7) and triglycerides (TG) levels (WMD: -2.85 mg/dl, 95% CI: -9.3 to 3.6) did not alter in DHEA group compared to the control, but HDL-C levels significantly reduced in DHEA group (WMD: -3.1 mg/dl, 95% CI: -4.9 to -1.3). In addition, a significant reduction in HDL-C values was observed in studies comprising women (WMD: -5.1 mg/dl, 95% CI: -7.2 to -3) but not in males (WMD: 0.13 mg/dl, 95% CI: -1.4 to 1.7).
CONCLUSIONS: Overall, supplementation with DHEA did not change circulating values of TC, LDL-C and TG, whereas it may decrease HDL-C levels. Further long-term RCTs are required to investigate the effects of DHEA particularly on major adverse cardiac events.
METHODS: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes.
RESULTS: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24-42%) and 13% (95% CI: 6-20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively.
CONCLUSION: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.
METHODS: A comprehensive systematic search was carried out in PubMed/MEDLINE, Web of Science, SCOPUS and Embase from inception until June 2019. Weighted mean difference (WMD) with the 95 % CI were applied for estimating the effects of metformin on serum IGF-1 levels.
RESULTS: 11 studies involving a total of 569 individuals reported changes in IGF-1 plasma concentrations as an outcome measure. Pooled results demonstrated an overall non-significant decline in IGF-1 following metformin intake (WMD: -8.292 ng/ml, 95 % CI: -20.248, 3.664, p = 0.174) with heterogeneity among (p = 0.000,I2 = 87.1 %). The subgroup analyses displayed that intervention duration <12 weeks on children (WMD:-55.402 ng/ml, 95 % CI: -79.845, -30.960, I2 = 0.0 %) significantly reduced IGF-1. Moreover, in age 18 < years older metformin intake (WMD: 15.125 ng/ml, 95 % CI: 5.522, 24.729, I2 = 92.5 %) significantly increased IGF-1 than 18 ≤ years older (WMD:-1.038 ng/ml, 95 % CI: -3.578,1.502,I2 = 78.0 %). Following dose-response evaluation, metformin intake reduced IGF-1 (coefficient for dose-response analysis= -13.14, P = 0.041 and coefficient for liner analysis= -0.066, P = 0.038) significantly based on treatment duration.
CONCLUSION: We found in children, intervention duration <12 weeks yielded significant reductions in IGF-1, whilst paradoxically, in participants >18 years old, metformin intake significantly increased IGF-1. We suggest that caution be taken when interpreting the findings of this review, particularly given the discordant supplementation practices between children and adults.
METHOD: A comprehensive search of Medline, Embase, Web of Science, and the Cochrane Library was conducted from database inception to October, 2023. Included studies were randomized controlled trials (RCTs) reporting the effects of exercise on JIA patients. Two independent reviewers assessed the literature quality using the Cochrane Collaboration's risk of bias tool. Standardized mean differences (SMD) were combined using random or fixed effects models. The level of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.
RESULT: Five RCTs met the inclusion criteria, containing 216 female participants and 90 males. The meta-analysis results showed that exercise had no significant effect on JIA patients based on the Child Health Assessment Questionnaire (CHAQ) (SMD=-0.32, 95%CI: -0.83, 0.19; I2 = 73.2%, P = 0.011) and Quality of Life (QoL) (SMD = 0.27, 95%CI: -0.04, 0.58; I2 = 29.4%, P = 0.243) and no significant effect on peak oxygen uptake (VO2peak). However, exercise significantly reduced visual analog scale (VAS) pain scores in JIA patients (SMD = 0.50, 95%CI: -0.90, -0.10; I2 = 50.2%, P = 0.134). The quality of evidence assessed by GRADE was moderate to very low.
CONCLUSION: Exercise does not significantly affect the quality of life and exercise capacity in JIA patients but may relieve pain. More RCTs are needed in the future to explore the effects of exercise on JIA.
OBJECTIVE: To evaluate the efficacy of exercise and its potential determinants for pain, function, performance, and quality of life (QoL) in knee and hip osteoarthritis (OA).
METHODS: We searched 9 electronic databases (AMED, CENTRAL, CINAHL, EMBASE, MEDLINE Ovid, PEDro, PubMed, SPORTDiscus and Google Scholar) for reports of randomised controlled trials (RCTs) comparing exercise-only interventions with usual care. The search was performed from inception up to December 2017 with no language restriction. The effect size (ES), with its 95% confidence interval (CI), was calculated on the basis of between-group standardised mean differences. The primary endpoint was at or nearest to 8 weeks. Other outcome time points were grouped into intervals, from<1 month to≥18 months, for time-dependent effects analysis. Potential determinants were explored by subgroup analyses. Level of significance was set at P≤0.10.
RESULTS: Data from 77 RCTs (6472 participants) confirmed statistically significant exercise benefits for pain (ES 0.56, 95% CI 0.44-0.68), function (0.50, 0.38-0.63), performance (0.46, 0.35-0.57), and QoL (0.21, 0.11-0.31) at or nearest to 8 weeks. Across all outcomes, the effects appeared to peak around 2 months and then gradually decreased and became no better than usual care after 9 months. Better pain relief was reported by trials investigating participants who were younger (mean age<60 years), had knee OA, and were not awaiting joint replacement surgery.
CONCLUSIONS: Exercise significantly reduces pain and improves function, performance and QoL in people with knee and hip OA as compared with usual care at 8 weeks. The effects are maximal around 2 months and thereafter slowly diminish, being no better than usual care at 9 to 18 months. Participants with younger age, knee OA and not awaiting joint replacement may benefit more from exercise therapy. These potential determinants, identified by study-level analyses, may have implied ecological bias and need to be confirmed with individual patient data.
DESIGN: Network meta-analysis.
DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.
RESULTS: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs).
CONCLUSIONS: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.
OBJECTIVES: To determine the effectiveness of rapamycin or rapalogs in people with tuberous sclerosis complex for decreasing tumour size and other manifestations and to assess the safety of rapamycin or rapalogs in relation to their adverse effects.
SEARCH METHODS: Relevant studies were identified by authors from the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, and clinicaltrials.gov. Relevant resources were also searched by the authors, such as conference proceedings and abstract books of conferences, from e.g. the Tuberous Sclerosis Complex International Research Conferences, other tuberous sclerosis complex-related conferences and the Human Genome Meeting. We did not restrict the searches by language as long as English translations were available for non-English reports.Date of the last searches: 14 March 2016.
SELECTION CRITERIA: Randomized or quasi-randomized studies of rapamycin or rapalogs in people with tuberous sclerosis complex.
DATA COLLECTION AND ANALYSIS: Data were independently extracted by two authors using standard acquisition forms. The data collection was verified by one author. The risk of bias of each study was independently assessed by two authors and verified by one author.
MAIN RESULTS: Three placebo-controlled studies with a total of 263 participants (age range 0.8 to 61 years old, 122 males and 141 females, with variable lengths of study duration) were included in the review. We found high-quality evidence except for response to skin lesions which was judged to be low quality due to the risk of attrition bias. Overall, there are 175 participants in the treatment arm (rapamycin or everolimus) and 88 in the placebo arm. Participants all had tuberous sclerosis complex as proven by consensus diagnostic criteria as a minimum. The quality in the description of the study methods was mixed, although we assessed most domains as having a low risk of bias. Blinding of treatment arms was successfully carried out in all of the studies. However, two studies did not report allocation concealment. Two of the included studies were funded by Novartis Pharmaceuticals.Two studies (235 participants) used oral (systemic) administration of everolimus (rapalog). These studies reported response to tumour size in terms of the number of individuals with a reduction in the total volume of tumours to 50% or more relative to baseline. Significantly more participants in the treatment arm (two studies, 162 participants, high quality evidence) achieved a 50% reduction in renal angiomyolipoma size, risk ratio 24.69 (95% confidence interval 3.51 to 173.41) (P = 0.001). For the sub-ependymal giant cell astrocytoma, our analysis of one study (117 participants, high quality evidence) showed significantly more participants in the treatment arm achieved a 50% reduction in tumour size, risk ratio 27.85 (95% confidence interval 1.74 to 444.82) (P = 0.02). The proportion of participants who showed a skin response from the two included studies analysed was significantly increased in the treatment arms, risk ratio 5.78 (95% confidence interval 2.30 to 14.52) (P = 0.0002) (two studies, 224 participants, high quality evidence). In one study (117 participants), the median change of seizure frequency was -2.9 in 24 hours (95% confidence interval -4.0 to -1.0) in the treatment group versus -4.1 in 24 hour (95% confidence interval -10.9 to 5.8) in the placebo group. In one study, one out of 79 participants in the treatment group versus three of 39 in placebo group had increased blood creatinine levels, while the median percentage change of forced expiratory volume at one second in the treatment arm was -1% compared to -4% in the placebo arm. In one study (117 participants, high quality evidence), we found that those participants who received treatment had a similar risk of experiencing adverse events compared to those who did not, risk ratio 1.07 (95% confidence interval 0.96 - 1.20) (P = 0.24). However, as seen from two studies (235 participants, high quality evidence), the treatment itself led to significantly more adverse events resulting in withdrawal, interruption of treatment, or reduction in dose level, risk ratio 3.14 (95% confidence interval 1.82 to 5.42) (P < 0.0001).One study (28 participants) used topical (skin) administration of rapamycin. This study reported response to skin lesions in terms of participants' perception towards their skin appearance following the treatment. There was a tendency of an improvement in the participants' perception of their skin appearance, although not significant, risk ratio 1.81 (95% confidence interval 0.80 to 4.06, low quality evidence) (P = 0.15). This study reported that there were no serious adverse events related to the study product and there was no detectable systemic absorption of the rapamycin during the study period.
AUTHORS' CONCLUSIONS: We found evidence that oral everolimus significantly increased the proportion of people who achieved a 50% reduction in the size of sub-ependymal giant cell astrocytoma and renal angiomyolipoma. Although we were unable to ascertain the relationship between the reported adverse events and the treatment, participants who received treatment had a similar risk of experiencing adverse events as compared to those who did not receive treatment. Nevertheless, the treatment itself significantly increased the risk of having dose reduction, interruption or withdrawal. This supports ongoing clinical applications of oral everolimus for renal angiomyolipoma and subependymal giant cell astrocytoma. Although oral everolimus showed beneficial effect on skin lesions, topical rapamycin only showed a non-significant tendency of improvement. Efficacy on skin lesions should be further established in future research. The beneficial effects of rapamycin or rapalogs on tuberous sclerosis complex should be further studied on other manifestations of the condition.
METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo.
RESULTS: Between February 2013 and May 2016, we recruited 27,395 participants from 602 centres in 33 countries; 17,598 participants were included in the pantoprazole vs placebo comparison. At baseline, the mean age was 68.2 years, 22.0% were female, 90.6% had CAD, and 27.3% had PAD.
CONCLUSIONS: COMPASS will provide information on the efficacy and safety of rivaroxaban, alone or in combination with aspirin, in the long-term management of patients with stable CAD or PAD, and on the efficacy and safety of pantoprazole in preventing upper GI complications in patients receiving antithrombotic therapy.
MATERIALS AND METHODS: Randomized controlled comparing MIE versus OE were searched from PubMed and other electronic databases between January 1991 and March 2019. Thirteen outcome variables were analyzed. Random effects model was used to calculate the effect size. The meta-analysis was prepared in accordance with PRISMA guidelines.
RESULTS: Four randomized controlled trials totaling 569 patients were analyzed. For MIE, there was a significantly reduction of 67% in the odds of pulmonary complications. For operating time, MIE was nonsignificantly 29 minutes longer. MIE was associated with nonsignificantly less blood loss of 443.98 mL. There was nonsignificant 60% reduction in the odds of total complications and 51% reduction in the odds of medical complications favoring MIE group. For delayed gastric emptying, there was a nonsignificant reduction of 75% in the odds ratio favoring the MIE group. For postoperative anastomotic leak, there was a nonsignificant increase of 48% in the odds ratio for MIE group. For gastric necrosis, chylothorax, reintervention and 30-day mortality, no difference was observed for both groups. There was a nonsignificant reduction in the length of hospital stay of 7.98 days and intensive care unit stay of 2.7 days favoring MIE.
CONCLUSIONS: MIE seems to be superior to OE for only pulmonary complications. All the other perioperative variables were comparable however, the trend is favoring the MIE. Therefore, the routine use of MIE presently may only be justifiable in high volume esophagogastric units.
MATERIALS AND METHODS: We identified RCTs for SUI interventions published between January 2015 and July 2017. We listed the objective and subjective outcome measures used in eligible trials in the literature search. Using data from our RCT conducted from 2013 to 2016 evaluating pulsed magnetic stimulation for SUI, we analysed the correlation between all measures.
RESULTS: A total of 45 RCTs were included; 28 (62%) involved surgical interventions. The most frequently used objective and subjective measures were the cough stress test and International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), respectively. In all, 24 different validated questionnaires were administered in the 42 studies that used subjective outcome measure. Analyses of measures used in our trial showed that all measures were significantly correlated with each other except for pelvic floor muscle function. The ICIQ-UI SF showed the highest correlation coefficients (0.587-0.733) with all outcome measures.
CONCLUSION: The outcome measures used in recent trials were inconsistent. The ICIQ-UI SF had the highest correlation with all measures in our trial; however, further studies evaluating correlation of measures in other patient cohorts are needed to corroborate our present results. We propose the use of ICIQ-UI SF, as the most relevant outcome measure, in future trials evaluating efficacy of SUI interventions.