Search For Randomized Controlled Trials Research Articles

Effects of exercise intervention on balance function in children with cerebral palsy: a systematic review and meta-analysis of randomized controlled trials

ObjectiveTo determine the effectiveness of exercise intervention on postural balance, gait parameters, and muscle strength in children with cerebral palsy by quantifying the information from randomized controlled trials (RCTs).MethodsWe conducted a systematical search for RCTs from the databases, including PubMed, ISI Web of Science, and Scopus using a between-group design involving children with cerebral palsy and assessing the effect of exercise intervention on postural balance, gait parameters, and muscle strength. The specified inclusion criteria were determined by the PICOS tool. The outcomes of included studies were evaluated by meta-analysis, and subgroup and sensitivity analyses were conducted to analyze the observed heterogeneities using Review Manager 5.4 and Stata version 18.0. The revised Cochrane risk of bias tool for randomized trials (RoB 2) was used to evaluate the risk of bias and quality of the included studies.ResultsTwenty-four studies were included in this meta-analysis, with 579 children with cerebral palsy. Exercise intervention showed a statistically significant favorable effect on gross motor function (SMD = 0.32; 95%CI [0.03 to 0.61]; I2 = 16%), anteroposterior stability index (SMD = -0.93; 95%CI [-1.69 to -0.18]; I2 = 80%), and mediolateral stability index (SMD = -0.60; 95%CI [-1.16 to -0.03]; I2 = 73%) compared to control group among children with cerebral palsy. None of the above meta-analyses exhibited publication bias, as indicated by Egger’s test with p-values greater than 0.05 for all.ConclusionsExercise is effective in improving gross motor function and balance in children with cerebral palsy. Due to the lack of studies examining the efficacy of each exercise type, we are unable to provide definitive training recommendations.

Postoperative antibiotic prophylaxis for percutaneous nephrolithotomy and risk of infection: a systematic review and meta-analysis.

The aim of this study is to perform a high-quality meta-analysis using only randomized controlled trials (RCT) to better define the role of postoperative antibiotics in patients undergoing percutaneous nephrolithotomy (PCNL). A literature search for RCTs in EMBASE, PubMed, and Web of Science up to May 2023 was conducted following the PICO framework: Population-adult patients who underwent PCNL; Intervention-postoperative antibiotic prophylaxis until nephrostomy tube withdrawal; Control-single dose of antibiotic during the induction of anesthesia; and Outcome-systemic inflammatory response syndrome (SIRS) or sepsis and fever after PCNL. The protocol was registered on the PROSPERO database (CRD42022361579). We calculated odds ratios (OR) and 95% confidence intervals (CI). A random-effects model was employed, and the alpha risk was defined as < 0.05. Seven articles, encompassing a total of 629 patients, were included in the analysis. The outcome of SIRS or sepsis was extracted from six of the included studies, while the outcome of postoperative fever was extracted from four studies. The analysis revealed no statistical association between the use of postoperative antibiotic prophylaxis until nephrostomy tube withdrawal and the occurrence of SIRS/sepsis (OR 1.236, 95% CI 0.731 - 2.089, p=0.429) or fever (OR 2.049, 95% CI 0.790 - 5.316, p=0.140). Our findings suggest that there is no benefit associated with the use of postoperative antibiotic prophylaxis until nephrostomy tube withdrawal in patients undergoing percutaneous nephrolithotomy (PCNL). We recommend that antibiotic prophylaxis should be administered only until the induction of anesthesia in PCNL.

What are the emerging trends in dental composite materials in permanent teeth with occlusal cavities: self-adhesive vs traditional?

The research is a systematic review and meta-analysis of randomized controlled trials (RCTs). The study aimed to compare the clinical outcomes of self-adhesive flowable composite resins (SAFCs) versus conventional flowable composite resins (FCs) used in occlusal cavity restorations in permanent teeth. This research included a search for RCTs. Multiple databases were systematically searched for RCTs with a minimum 1-year follow-up comparing SAFCs to FCs. Outcomes evaluated were retention, secondary caries, marginal adaptation, marginal discoloration, and postoperative sensitivity based on modified USPHS criteria. Risk of bias was assessed using Cochrane RoB 2 tool. Random effects meta-analyses were conducted where applicable. Certainty of evidence was rated using GRADE approach. Five RCTs (four parallel and one split mouth) comprising 138 patients were included. During 1- and 2-year recalls, there were generally no significant differences in clinical performance between SAFCs and FCs. However, FCs applied using the etch-and-rinse technique demonstrated statistically better marginal adaptation at 2 years (3 studies, RR 3.21, 95% CI 1.50-6.83) and marginal discoloration (4 studies, RR 3.40, 95% CI 1.10-10.48). The overall quality of evidence ranged from low to moderate. SAFCs showed comparable short-term outcomes to FCs in treating occlusal cavities. Further high-quality RCTs with longer follow-up are warranted to confirm long-term performance of SAFCs. Use of separate enamel etching may improve marginal adaptation and discoloration with FCs.

Statistical Power of Randomized Controlled Trials in Trauma Surgery.

Our purpose was to conduct a bibliometric study investigating the prevalence of underpowered randomized controlled trials (RCTs) in trauma surgery. A medical librarian conducted a search of RCTs in trauma published from 2000 to 2021. Data extracted included study type, sample size calculation, and power analyses. Post hoc calculations were performed using a power of 80% and an alpha level of 0.05. A CONSORT checklist was then tabulated from each study as well as a fragility index for studies with statistical significance. In total 187 RCTs from multiple continents and 60 journals were examined. A total of 133 (71%) were found to have "positive" findings consistent with their hypothesis. When evaluating their methods, 51.3% of articles did not report how they calculated their intended sample size. Of those that did, 25 (27%) did not meet their target enrollment. When examining post hoc power, 46%, 57%, and 65% were adequately powered to detect small, medium, and large effect sizes, respectively. Only 11% of RCTs had complete adherence with CONSORT reporting guidelines and the average CONSORT score was 19 out of 25. For positive superiority trials with binary outcomes, the fragility index median (interquartile range) was 2 (2 to 8). A concerningly large proportion of recently published RCTs in trauma surgery do not report a priori sample size calculations, do not meet enrollment targets, and are not adequately powered to detect even large effect sizes. There exists opportunity for improvement of trauma surgery study design, conduct, and reporting.

Use of melatonin in children and adolescents with idiopathic chronic insomnia: a systematic review, meta-analysis, and clinical recommendation.

Melatonin prescriptions for children and adolescents have increased substantially during the last decade. Existing clinical recommendations focus on melatonin as a treatment for insomnia related to neurodevelopmental disorders. To help guide clinical decision-making, we aimed to construct a recommendation on the use of melatonin in children and adolescents aged 5-20 years with idiopathic chronic insomnia. A systematic search for guidelines, systematic reviews and randomised controlled trials (RCT) were performed in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A search for adverse events in otherwise healthy children and adolescents was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 18, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (5-20 years of age) with idiopathic chronic insomnia, in whom sleep hygiene practices have been inadequate and melatonin was tested. There were no restrictions on dosage, duration of treatment, time of consumption, or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, all-cause dropouts, and non-serious adverse events. Outcomes were assessed at different time points to assess short-term and long-term effects. Meta-analysis was performed using inverse variance random-effects model and risk of bias was assessed using Cochrane risk of bias tool. If possible, funnel plots would be constructed to investigate publication bias. Heterogeneity was calculated via I2 statistics. A multidisciplinary guideline panel formulated the recommendation according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was subsequently used to discuss the feasibility and acceptance of the constructed recommendation alongside the impact on resources and equity. The protocol is registered with the Danish Health Authority. We included eight RCTs with 419 children and adolescents with idiopathic chronic insomnia. Melatonin led to a moderate increase in total sleep time by 30.33min (95% confidence interval (CI) 18.96-41.70, 4 studies, I2=0%) and a moderate reduction in sleep latency by 18.03min (95% CI-26.61 to-9.44, 3 studies, I2=0%), both as assessed by sleep diary. No other beneficial effects were found. None of the studies provided information on serious adverse events, yet the number of participants experiencing non-serious adverse events was increased (Relative risk 3.44, 95% CI 1.25-9.42, 4 studies, I2=0%). Funnel plots were not constructed due to the low number of studies. The certainty of evidence was very low on the quality of sleep and low for daytime functioning. Evidence of very low certainty shows that benefits are limited and unwanted events are likely when melatonin is used to treat otherwise healthy children and adolescents with chronic insomnia. Melatonin should never be the first choice of treatment for this particular population, yet carefully monitored short-term use may be considered if sleep hygiene practices and non-pharmacological interventions have proven inadequate, and only if daytime function is compromised. The Danish Health Authority and the Parker Institute, Bispebjerg and Frederiksberg Hospital supported by the Oak Foundation.

Practitioner Review: Common elements in treatments for youth suicide attempts and self-harm - a practitioner review based on review of treatment elements associated with intervention benefits.

Adopting a common elements approach, this practitioner review aims to highlight specific treatment elements that are common to interventions with demonstrated benefits in randomized controlled trials (RCTs) for reducing suicide attempts and self-harm in youth. Identification of common treatment elements among effective interventions offers a key strategy for clarifying the most robust features of effective interventions and improving our ability to implement effective treatment and decrease the lag between scientific advances and clinical care. A systematic search of RCTs evaluating interventions targeting suicide/self-harm in youth (ages 12-18) yielded a total of 18 RCTs assessing 16 different manualized interventions. An open coding process was used to identify common elements present within each intervention trial. Twenty-seven common elements were identified and classified into format, process, and content categories. All trials were coded for the inclusion of these common elements by two independent raters. RCTs were also classified into those where trial results supported improvements in suicide/self-harm behavior (n=11 supported trials) and those without supported evidence (n=7 unsupported trials). Compared with unsupported trials, the 11 supported trials shared the following elements: (a) inclusion of therapy for both the youth and family/caregivers; (b) an emphasis on relationship-building and the therapeutic alliance; (c) utilization of an individualized case conceptualization to guide treatment; (d) provided skills training (e.g. emotion regulation skills) to both youth and their parents/caregivers; and (e) lethal means restriction counseling as part of self-harm monitoring and safety planning. This review highlights key treatment elements associated with efficacy that community practitioners can incorporate in their treatments for youth presenting with suicide/self-harm behaviors.

Automated Digital Interventions and Smoking Cessation: Systematic Review and Meta-analysis Relating Efficiency to a Psychological Theory of Intervention Perspective.

Smoking remains a highly significant preventable global public health problem. In this context, digital interventions offer great advantages in terms of a lack of biological side effects, possibility of automatic delivery, and consequent human resource savings relative to traditional interventions. Such interventions have been studied in randomized controlled trials (RCTs) but have not been systematically reviewed with the inclusion of text-based and multiplatform-based interventions. In addition, this area has not been evaluated from the perspective of the psychological theoretical basis of intervention. The aim of this paper is to assess the efficiency of digital interventions in RCT studies of smoking cessation and to evaluate the effectiveness of the strategies used for digital interventions. An electronic search of RCTs was conducted using PubMed, Embase, and the Cochrane Library by June 30, 2021. Eligible studies had to compare automated digital intervention (ADI) to the use of a self-help guideline or no intervention. Participants were current smokers (aged 16 years or older). As the main outcome, abstinence after endpoint was extracted from the studies. Systematic review and meta-analysis were conducted to assess the efficiency of ADIs. Metaregressions were conducted to assess the relationship between intervention theory and effectiveness. A total of 19 trials (15,472 participants) were included in the analysis. The overall abstinence rate (95% CI) at the endpoint was 17.8% (17.0-18.7). The overall risk ratio of the intervention group compared to the controls at the endpoint was 17.8% (17.0-18.7). Cochrane risk-of-bias tool for randomized trials (ROB 2) suggested that most of the studies had a low risk of bias (56.3%). Psychological theory-related constructs or predictors, which refer to other theory-based concepts (rather than only behavioral theory) such as craving or anxiety, are associated with effectiveness. This study found that ADI had a clear positive effect compared to self-help guidelines or to no intervention, and effectiveness was associated with theory-related constructs or predictors. ADIs should be promoted by policy makers and clinical practitioners to address the huge gap between the need for smoking cessation and availability of traditional treatment resources. Possible increases in ADI efficiency may be achieved by optimally integrating psychotherapeutic theories and techniques. PROSPERO CRD42021256593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=256593.

The Efficacy of Telemedicine for Secondary Prevention and Management Among Stroke Survivors: A Systematic Review and Meta-analysis

Stroke has high mortality and high recurrence rate. Telemedicine usage is rapidly growing as a strategy to optimize stroke secondary prevention by managing stroke risk factors. In order to comprehensively assess the impact of telemedicine intervention, an updated review of more outcomes is required. This systematic review and meta-analysis of randomized controlled trials (RCTs) aim to assess the telemedicine effects on systolic blood pressure, diastolic blood pressure, stroke recurrence, and mortality in post-stroke patients. A literature search of RCTs related to telemedicine intervention from PubMed, Science Direct, Scopus, Web of Science, and ProQuest from 2018 to 2022 was included in this study. The quality of the study was evaluated using the Cochrane RoB 2 tool. We presented the pooling analysis of our result in the form of mean difference (MD) and odd ratio (OR) with 95% CI using RevMan 5.4 software. Six trials involving 3,942 patients met the eligibility criteria to conduct the meta-analysis. Telemedicine intervention had a significant effect on the change of systolic (MD -6.05; 95% CI -6.23, -5.87; p < 0.00001; I2=84%) and diastolic (MD -2.76; 95% CI -4.13, -1.39; p < 0.0001; I2=89%) blood pressure control. Telemedicine intervention was also associated with lower stroke recurrence (OR 0.82; 95% CI 0.42, 1.59; p=0.55; I2= 70%) and mortality rate (OR 0.87; 95% CI 0.68, 1.12; p=0.28; I2=0%). Therefore, telemedicine applications may be a promising strategy to optimize the implementation of stroke secondary prevention. More up-to-date trials with higher quality are needed to confirm our findings and assess the other outcomes of telemedicine intervention, such as cost-effectiveness, medical adherence, and quality of life outcomes.

Trends in research on pain relief during oocyte retrieval for IVF/ICSI: a systematic, methodological review.

STUDY QUESTIONWhat is the methodological validity and usefulness of randomized controlled trials (RCTs) on pain relief during oocyte retrieval for IVF and ICSI?SUMMARY ANSWERKey methodological characteristics such as randomization, allocation concealment, primary outcome measure and sample size calculation were inadequately reported in 33–43% of the included RCTs, and a broad heterogeneity is revealed in the studied outcome measures.WHAT IS KNOWN ALREADYA Cochrane review on conscious sedation and analgesia for women undergoing oocyte retrieval concluded that the overall quality of evidence was low or very low, mainly owing to poor reporting. This, and heterogeneity of studied outcome measures, limits generalizability and eligibility of results for meta-analysis.STUDY DESIGN, SIZE, DURATIONFor this review, a systematic search for RCTs on pain relief during oocyte retrieval was performed on 20 July 2020 in CENTRAL CRSO, MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, WHO ICTRP, Web of Science, Portal Regional da BVS and Open Grey.PARTICIPANTS/MATERIALS, SETTING, METHODSRCTs with pain or patient satisfaction as an outcome were included and analysed on a set of methodological and clinical characteristics, to determine their validity and usefulness.MAIN RESULTS AND THE ROLE OF CHANCEScreening of 2531 articles led to an inclusion of 51 RCTs. Randomization was described inadequately in 33% of the RCTs. A low-risk method of allocation concealment was reported in 55% of the RCTs. Forty-nine percent of the RCTs reported blinding of participants, 33% of blinding personnel and 43% of blinding the outcome assessor. In 63% of the RCTs, the primary outcome was stated, but a sample size calculation was described in only 57%. Data were analysed according to the intention-to-treat principle in 73%. Treatment groups were not treated identically other than the intervention of interest in 10% of the RCTs. The primary outcome was intraoperative pain in 28%, and postoperative pain in 2%. The visual analogue scale (VAS) was the most used pain scale, in 69% of the RCTs in which pain was measured. Overall, nine other scales were used. Patient satisfaction was measured in 49% of the RCTs, for which 12 different methods were used. Occurrence of side-effects and complications were assessed in 77% and 49% of the RCTs: a definition for these was lacking in 13% and 20% of the RCTs, respectively. Pregnancy rate was reported in 55% of the RCTs and, of these, 75% did not adequately define pregnancy. To improve the quality of future research, we provide recommendations for the design of future trials. These include use of the VAS for pain measurement, use of validated questionnaires for measurement of patient satisfaction and the minimal clinically relevant difference to use for sample size calculations.LIMITATIONS, REASONS FOR CAUTIONConsensus has not been reached on some methodological characteristics, for which we formulated recommendations. To prevent further heterogeneity in research on this topic, recommendations were formulated based on expert opinion, or on the most used method thus far. Future research may provide evidence to base new recommendations on.WIDER IMPLICATIONS OF THE FINDINGSUse of the recommendations given for design of trials on this topic can increase the generalizability of future research, increasing eligibility for meta-analyses and preventing wastefulness.STUDY FUNDING/COMPETING INTEREST(S)No specific funding was obtained for this study. S.B. reports being the editor-in-chief of Human Reproduction Open. For this manuscript, he was not involved with the handling process within Human Reproduction Open, or with the final decision. Furthermore, S.B. reports personal fees from Remuneration from Oxford University Press as editor-in-chief of Human Reproduction Open, personal fees from Editor and contributing author, Reproductive Medicine for the MRCOG, Cambridge University Press. The remaining authors declare no conflict of interest in relation to the work presented.TRIAL REGISTRATION NUMBERNot applicable.

PARP Inhibitors for the Treatment of BRCA1/2-Mutated Metastatic Breast Cancer: A Systematic Review and Meta-analysis.

The PARP inhibitors (PARPis) olaparib and talazoparib are currently approved for the treatment of deleterious germline BRCA1/2-mutated (gBRCA+) metastatic breast cancer (MBC). These approvals were based on improvements in progression-free survival (PFS) observed in two randomized controlled trials (RCTs). Other PARPis, such as veliparib and niraparib, have also been studied. We conducted this meta-analysis of RCTs to assess the PFS and overall survival (OS) benefits of PARPis in gBRCA + MBC. We performed a systematic search for RCTs using the Cochrane Library, PubMed, Embase, and Web of Science databases up to March 2021. Only phase II and III RCTs evaluating PFS and OS for PARPis alone or in combination with chemotherapy (CT) and comparing the findings with standard CT were included in this meta-analysis. Pooled analysis of the hazard ratio (HR) was performed with RevMan v5.4 using a random effects method. Five RCTs with a total of 1563 BRCA-mutated MBC patients were included in this meta-analysis. Temozolomide was used in the treatment arm in the BROCADE trial. Since temozolomide has limited effects on breast cancer, this arm was excluded from our meta-analysis. A statistically significant increase in PFS was observed in the PARPi group compared to the standard CT group (HR, 0.64; 95% CI, 0.56-0.74; P < 0.00001). However, the differences in OS did not reach statistical significance (HR, 0.89; 95% CI, 0.77-1.02; P = 0.09). Moreover, differences were not observed in the adverse event profile between the two groups (odds ratio, 1.18; 95% CI, 0.84-1.64; P = 0.33). The results of our meta-analysis confirm the previously reported PFS benefit of PARPis over standard CT. PARPis lead to superior PFS in gBRCA + MBC when used alone or in combination with standard CT. The OS benefit is similar between PARPis and standard CT. Ongoing trials are evaluating the benefits of PARPis in early stage gBRCA + BC.

A Retrospective Analysis of Randomized Controlled Trials on Traumatic Brain Injury: Evaluation of CONSORT Item Adherence.

Traumatic brain injury (TBI) contributes to death and disability, resulting in an enormous individual and socio-economic challenges. Despite huge efforts, there are still controversies on treatment strategies and early outcome estimation. We evaluate current randomized controlled trials (RCTs) on TBI according to their fulfillment of the CONSORT (Consolidated Statement of Reporting Trials) statement’s criteria as a marker of transparency and the quality of study planning and realization. A PubMed search for RCTs on TBI (January 2014–December 2019) was carried out. After screening of the abstracts (n = 1.926), the suitable full text manuscripts (n = 72) were assessed for the fulfillment of the CONSORT criteria. The mean ratio of consort statement fulfillment was 59% (±13%), 31% of the included studies (n = 22) complied with less than 50% of the CONSORT criteria. Citation frequency was moderately related to ratio of CONSORT item fulfillment (r = 0.4877; p < 0.0001) and citation frequency per year (r = 0.5249; p < 0.0001). The ratio of CONSORT criteria fulfillment was associated with the impact factor of the publishing journal (r = 0.6428; p < 0.0001). Essential data for study interpretation, such as sample size determination (item 7a), participant flow (item 13a) as well as losses and exclusions (item 13b), were only reported in 53%, 60% and 63%, respectively. Reporting and methodological aspects in RCTs on TBI still may be improved. Thus, the interpretation of study results may be hampered due to methodological weaknesses.

Omalizumab for the treatment of allergic rhinitis: a systematic review and meta-analysis.

Allergic rhinitis (AR), an IgE mediated inflammatory disease, significantly impacts quality of life of a considerable proportion of the general population. Omalizumab, a humanized monoclonal antibody against IgE, has been evaluated for both seasonal and perennial AR. We aimed to assess the efficacy and safety of omalizumab in randomized controlled trials (RCTs) in inadequately controlled AR. We conducted a systematic literature search of RCTs evaluating the safety and efficacy of omalizumab in AR. We synthesized evidence for clinical improvement of AR symptoms, quality of life, reduction of the use of rescue medication, and adverse events. The systematic search returned 289 articles, of which 12 RCTs were eligible for data extraction and meta-analysis. Omalizumab reduced the Daily Nasal Symptom Severity Score (DNSSS) by a summary standardized mean difference of -0.41 points with large heterogeneity; omalizumab significantly reduced the DNSSS both in the 3 cedar pollen-induced AR trials by -0.97 points and to a lower extent in the remaining five non-cedar trials by -0.19 points. Omalizumab also improved the Daily Ocular Symptom Severity Score (DOSSS) by a summary standardized mean difference of -0.30 points with large heterogeneity; the Rhino-conjunctivitis Quality of Life Questionnaire by a summary standardized mean difference of -0.45 points with no heterogeneity and the mean daily consumption of rescue antihistamines by a summary standardized mean difference of -0.21 with large heterogeneity. No statistically significant difference in the occurrence of adverse events was observed between omalizumab and placebo. Our findings further support the efficacy and safety of omalizumab in the management of patients with allergic rhinitis inadequately controlled with a conventional treatment.

Effects of probiotics on body adiposity and cardiovascular risk markers in individuals with overweight and obesity: A systematic review and meta-analysis of randomized controlled trials

Evidence suggests that gut microbiota is a potential factor in the pathophysiology of both obesity and related metabolic disorders. While individual randomized controlled trials (RCTs) have evaluated the effects of probiotics on adiposity and cardiovascular disease (CVD) risk factors in subjects with overweight and obesity, the results are inconsistent. Thus, this systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation on body weight, body adiposity and CVD risk markers in overweight and obese subjects. A systematic search for RCTs published up to December 2020 was conducted in MEDLINE (via PubMed), EMBASE, Scopus and LILACS. Meta-analysis using a random-effects model was chosen to analyze the impact of combined trials. Twenty-six RCTs (n=1720) were included. Data pooling showed a significant effect of probiotics in reducing body weight (MD:-0.70kg; 95%CI:-1.04,-0.35kg; P<0.0001), body mass index (BMI) (MD:-0.24kg/m2; 95%CI:-0.35,-0.12kg/m2; P=0.0001), waist circumference (WC) (MD:-1.13cm; 95%CI:-1.54,-0.73cm; P<0.0001), fat mass (MD:-0.71kg; 95%CI:-1.10,-0.32kg; P=0.0004), tumor necrosis factor-α (MD:-0.16pg/ml; 95%CI:-0.24,-0.08pg/ml; P=0.0001), insulin (MD:-0.85mcU/ml; 95%CI:-1.50,-0.21mcU/ml; P=0.010), total cholesterol (MD:-0.16mmol/l; 95%CI:-0.26,-0.05mmol/l; P=0.003) and LDL (MD:-0.09mmol/l; 95%CI:-0.16,-0.03mmol/l; P=0.006) compared with control groups. There was a significant decrease in body weight, BMI and WC in studies using both single and multi-bacterial species. Decreases in body adiposity parameters were only observed in studies using a probiotic dose of ≥ 1010CFU and for ≥8 weeks duration. The present meta-analysis suggests that probiotics consumption may be helpful for improving body weight, body adiposity and some CVD risk markers in individuals with overweight and obesity. The review was registered on PROSPERO (International prospective register of systematic reviews): CRD42020183136.

The Use of Multiple Primary Outcomes in Randomized Controlled Trials of Chinese Herbal Medicine.

Background Multiple primary outcomes are commonly used in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM). Analysis and interpretation of the results of CHM RCTs with many outcomes are not clear. No previous studies have systematically assessed the use of multiple primary outcomes in this area. This study aimed to assess the reporting of multiple primary outcomes and the statistical methods used to adjust multiplicity in RCTs of CHM. Methods Search for RCTs of CHM published in English between January 2010 and December 2019 in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was undertaken. We randomly selected 20% of the included RCTs as the analyzing sample of this study. The number of multiple primary outcomes, the methods used to adjust the multiplicity in statistical analysis and sample size estimate, and the trial information were collected. For RCTs that adopted multiple primary outcomes without the multiplicity adjustment, we used Bonferroni correction to adjust. Results 227 CHM RCTs were included in our study. 92 (40.5%) failed to report what their primary outcome was. Of 135 (59.5%) RCTs that reported primary outcome, 93 (68.9%) reported one and 42 (31.1%) reported more than one primary outcome (range 2–5). Of 42 RCTs that reported multiple primary outcomes, only 5 adjusted for multiple outcomes. If multiplicity had been accounted for using Bonferroni correction, 10 (37.0%) RCTs that reported a significant result had demonstrated a nonsignificant result, giving the adjusted P value. Only one of the 42 RCTs calculated sample size based on multiple primary outcomes. Adopting multiple primary outcomes showed a slow growth trend with the publication year. The proportion of primary outcome reported explicitly in RCTs was different in terms of the nationality of the first author (P=0.004), in which mainland China has the lowest proportion (55.8%). The highest percentage of the studies with primary outcome reporting explicitation was mental and behavioural disorders (83.3%), and the most frequently adopting multiple primary outcomes were studies on the disease of the nervous system (66.7%). The percentage of reporting primary outcome explicitly was associated with sample size (P < 0.001); for the percentage of RCTs adopting multiple primary outcomes, there was no statistically significant difference (P=0.739). Conclusions Multiple primary outcomes are prevalent in CHM RCTs. However, appropriate methods are not usually taken in most of the analyses to safeguard the inferences against multiplicity. Sample size estimation based on multiple primary outcomes is still lacking. These issues complicate the interpretability of trial results and can lead to spurious conclusions. Guidelines to improve analyzing and reporting for multiple primary outcomes in CHM RCTs are warranted.

Comparison of Azacitidine and Decitabine in Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Network Meta-analysis

BackgroundMyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have a poor prognosis. Azacitidine (AZA) and decitabine (DAC) are the most widely used hypomethylating agents. However, few randomized controlled trials (RCTs) have compared AZA and DAC head to head in MDS or AML. This study intended to conduct a network meta-analysis to compare the 2 drugs to provide more guidance using evidence-based medicine. Patients and MethodsA comprehensive search for RCTs was performed till July 31, 2020. The network meta-analysis was conducted using the Markov chain Monte Carlo method. The primary endpoints were overall survival (OS) and the incidence of adverse events, and the secondary endpoints were complete remission (CR) rate, overall remission rate (ORR), and AML-free survival. There were 6 RCTs with 1072 MDS patients, and 3 RCTs with 1256 AML patients. ResultsIn MDS, AZA showed better AML-free survival (hazard ratio = 0.62; 95% CI, 0.43-0.9), whereas DAC had the possibility of achieving better CR and ORR, and AZA had the possibility of obtaining better OS with lower toxicity. As for elderly AML patients, DAC had the possibility of achieving superior CR, ORR, and OS, while the toxicity was relatively higher. Furthermore, subgroup analysis for patients ≥ 75 years old or of high risk in MDS suggested that AZA achieved better OS. ConclusionFor MDS, especially patients with intermediate or high risk disease with advanced age and poor general condition, AZA may be a better choice, while DAC may be of more benefit in elderly AML patients.

Abstract PS10-41: PARP inhibitors for treatment of BRCA positive metastatic breast cancer: A systematic review and meta-analysis

Abstract Background: PARP Inhibitors (inh), Olaparib and Talazoparib, are approved for deleterious germline BRCA mutated (gBRCA+) metastatic breast cancer (MBC). This approval was based on a progression-free survival (PFS) benefit seen in two randomized controlled trials (RCTs). Other PARP inh such as Veliparib and Niraparib have also been studied. We conducted this meta-analysis of RCTs aiming to assess PFS and OS of PARP inh in gBRCA+ MBC. Methods: We performed a systematic search for RCTs using Cochrane Library, PubMed, Embase, and Web of Science up to June 2020. Only phase II and III RCTs evaluating PFS for PARP inh alone or in combination with chemotherapy (CT) to standard CT were eligible for this meta-analysis. The pooled analysis of hazard ratio (HR) was performed with RevMan 5.4 software using random effect model. Results: A total of 5 RCTs including 1563 patients were included in this meta-analysis. Baseline study characteristics are listed in Table 1. The pooled HR for PFS was 0.77 (95%CI 0.55-1.09) and the pooled HR for OS was 0.96 (95%CI 0.80-1.16). The only statistically significant adverse event more common in PARP inh group was anemia (Odds Ratio, 3.01; CI95%, 1.14-7.93, P=0.03). (Table 2) Conclusion: The results of our meta-analysis confirmed the previously reported PFS benefit of PARP inh either alone or with standard CT when compared to standard CT alone in gBRCA+ MBC. PARP inh when combined with temozolomide did not show PFS benefit. OS benefit is not seen with PARP inh alone or with standard CT. Ongoing trials are evaluating the benefit of PARP inh in early stage gBRCA+ BC. Table 1: Baseline study characteristics as experimental group vs. control groupVCP: veliparib with carboplatin/paclitaxelVT: veliparib with temozolomidePCP: placebo plus carboplatin/paclitaxelNA: Not available** Subgroup germline BRCA+ pts (n=37, 13 vs 24) is used for PFS and OS analysis in this study.TrialsSample sizeExperimental groupControl groupECOG PS % (0/1/2)Previous CT no. (%)Previous platinum no. (%)Median PFS (mo)Median OS (mo)OlympiAD302 (205 Vs 97)OlaparibStandard CT (Capecitabine or Eribulin orVinorelbine)72.2/28.8/0 Vs 63.9/36.1/0146 (71.2) Vs 69 (71.1)60 (29.3) Vs 26 (26.8)7.0 Vs 4.219.3 Vs 17.1EMBRACA431 (287 Vs 144)TalazoparibStandard therapy53.3/44.3/2.1 Vs 58.3/39.6/1.4176(61.4) Vs 90(62.5)46 (16.0) Vs 30 (20.8)8.6 Vs 5.619.3 Vs 19.5BROCADE284 (97 Vs 99)VCPPCP92/5 Vs 93/623(23.7) Vs 37(37.4)NA14.1 Vs 12.328.3 Vs 25.9(94 Vs 99)VTPCP91/3 Vs 93/628(30.6) Vs 37 (37.4)NA7.4 Vs 12.319.1 Vs 25.9BROCADE-3509 (337 Vs 172)VCPPCPNA19%8%14.5 Vs 12.633.5 Vs 28.2SWOG S1416 **321Veliparib + CisplatinPlacebo + Cisplatin69/41Vs 57/4351(32) Vs 49(31)14(9) Vs 18(11)6.2 Vs 6.414.2 Vs 14.6BRAVO-NiraparibPhysician choice CTStudy was prematurely closed after an interim analysis showed too many patients were not completing the necessary assessments in the control arm, and it was no longer suitable as a registration trial. Table 2: Side effect profile of PARP inh arm vs. CT armNA: Not available**side effect includes all 154 pts in experimental arm and 149 in control armAdverse Events (%)OlympiAD EMBRACABROCADE(VCP &amp; VT Vs PCP)BROCADE-3SWOG S1416**Odds Ratio for Adverse EventsAnemia Grade ≥333 (16.1) Vs 4 (4.4)112 (39.2) Vs 6 (4.8)16 (17.2) &amp;7 (7.5) Vs 17 (17.7)91(27) Vs 29(17)35(23) vs 11(7)3.01 (1.14,7.93) P=0.03Neutropenia Grade ≥319 (9.3) Vs 24 (26.4)60 (20.9) Vs 44 (34.9)52(55.9) &amp;34(36.6) Vs 53 (55.2)175(52) Vs 86 (50)71(46) vs 29(19)0.80 (0.40, 1.62) P=0.53Leukopenia Grade ≥37(3.4) Vs 9 (9.9)19 (6.6) Vs 11(8.7)15(16.1) &amp;11(11.8) Vs 11 (11.5)NA42 (27) Vs 11 (7)1.19 (0.42,3.38) P=0.74Nausea/Vomiting Grade ≥30 Vs 1 (1.1)8 (2.7) Vs 4(3.2)2(2.2) &amp;5(5.4) Vs 3 (3.1)NA28(18) Vs 16(10)1.45 (0.85,2.46) P=0.17Diarrhea Grade ≥31 (0.5) Vs 02 (0.7) Vs 7 (5.6)4(4.3) &amp; 2(2.2) Vs 7(7.3)NANA0.33 (0.13, 0.85) P=0.02Fatigue Grade ≥36 (2.9) vs 1 (1.1)5 (1.7) Vs 4 (3.2)5(5.4) &amp;3(3.2) Vs 8(8.3)NA8(5) Vs 9(6)0.73 (0.40,1.33) P=0.30Treatment discontinuation due to any AE10 (4.9) Vs 7(7.7)17 (5.9) Vs 11 (8.7)NANA0.72 (0.39,1.34) P=0.30 Citation Format: Ranju Kunwor, Daniel P Silver, Saveri Bhattacharya, Rebecca Jaslow, Frederick Fellin, Ana Maria Lopez, Maysa M Abu-Khalaf. PARP inhibitors for treatment of BRCA positive metastatic breast cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-41.

Are Surgical Patients Satisfied With Remote Consultations? A Comparison of Remote Versus Conventional Outpatient Clinic Follow-Up for Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Access to remote appointments (RA) by telephone or video is increasing as technology advances and becomes more available to patients. This meta-analysis of randomized controlled trials (RCTs) aims to discover whether surgical patients are satisfied with RAs when compared with conventional outpatient clinics (OPC). A literature search of RCTs of surgical patient satisfaction of RAs versus OPC appointments was performed. The PubMed, EMBASE, OVID, Cochrane Library, and Google Scholar databases were searched to include articles from January 2000 to 2020. A random-effects meta-analysis model was used to compare outcomes. All 7 RCTs showed that patients were as satisfied with RAs as OPC appointments (RR = 1.00, [0.98-1.02]; P = .73). Furthermore, both patient cohorts would prefer RAs for future follow-up (RR = 2.29, [1.96-2.97]; P < .00001). One RCT found the cost to institutions was less in the RA group ($19.05 vs $52.76) and another found the patients would save $9.96 on transportation costs. The majority of RCTs suggested cost to patients and or institutions would be less for RA. In conclusion, surgical patients are satisfied with RAs and in fact would prefer them.

Evaluation of 'spin' in the abstracts and articles of randomizedcontrolled trials in pain literature and general anesthesia.

Aim: To evaluate the abstracts and articles of randomized controlled trials (RCTs)in pain literature and general anesthesia for the evidence of spin. Materials & methods: Following a priori protocol, we used a PubMed search for RCTsfrom a 2-year period. Data extracted using the Boutron spin definition for criteria. Results:A total of163 articles were identified as RCTswith clear primary and secondary end points.A total of33 trials were identified with nonsignificant primary end points.An18/33 were found to have spin (54.5%). The spin was identified in the results, title and conclusion 12/18, 3/18 and 3/18, respectively. Conclusion: Spin was found in 54% of pain RCTs. With sensitive clinical concerns, such as chronic pain, any misrepresentation of validity could prove to have significant clinical consequences.

78. The current incidence of adjacent segment pathology following cervical disc arthroplasty (CDA) or anterior cervical discectomy and fusion (ACDF): a systematic review and meta-analysis of randomized clinical trials

BACKGROUND CONTEXT The introduction of CDA has provided a biomechanically sound alternative to ACDF, helping to preserve motion and potentially reduce adjacent segment pathology. To date, studies have shown conflicting results on the true impact of ACDF and CDA on adjacent levels. PURPOSE To assess rates of radiographic adjacent segment degeneration (ASDeg) and symptomatic adjacent segment disease (ASDis), as well as reoperation rates due to adjacent segment pathology in patients who have undergone anterior cervical discectomy and fusion (ACDF) vs cervical disc arthroplasty (CDA). STUDY DESIGN/SETTING Meta-analysis of randomized controlled trials (RCTs). PATIENT SAMPLE A total of 18 studies were included in the final analysis, comprising 4,082 total patients with 1,854 patients who underwent ACDF and 2,454 who underwent CDA. OUTCOME MEASURES The pooled outcomes of interest included: adjacent segment degeneration, adjacent segment disease and reoperation for adjacent segment pathology. Adjacent segment degeneration was defined as changes on plain radiographs or magnetic resonance imaging (MRI) at segments adjacent to a previously operated level. Adjacent segment disease or symptomatic adjacent segment pathology was defined by persistent neck pain and new-onset radiculopathy/myelopathy. Symptomatic adjacent segment pathology requiring additional surgical intervention was categorized as reoperation due to adjacent segment pathology. METHODS A comprehensive search of RCTs was performed in PubMed from 2012 to 2019. Relevant studies included were assessed for quality using the Cochrane Beck Review Group guidelines. Rates of ASDeg, ASDis, and reoperation due to adjacent segment pathology were extracted and included in the final analysis. RESULTS Overall, ACDFs compared to CDAs had higher rates of radiographic adjacent segment degeneration (45.26% vs 31.91%), symptomatic ASDis (16.21% vs 10.96%), and reoperation (8.53% vs 5.26%, respectively; all p CONCLUSIONS Currently, CDA has lower rates of adjacent segment degeneration, disease, and reoperation rates compared to ACDF in those with at least 2 years follow-up. CDA may be a viable alternative to ACDF; however, further long-term studies are warranted to ensure consistency and establish longevity of our findings. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Effects of nutritional supplements on the re-infection rate of soil-transmitted helminths in school-age children: A systematic review and meta-analysis.

The effect of nutritional supplements on the re-infection rate of species-specific soil-transmitted helminth infections in school-aged children remains complex and available evidence on the subject matter has not been synthesized. The review included randomised controlled trials (RCTs) and cluster RCTs investigating food supplements on school-aged children between the age of 4-17 years. A search for RCTs was conducted on eight databases from inception to 12th June 2019. Cochrane Risk of Bias tool was used to assess the risk of bias in all included studies. Meta-analysis and narrative synthesis were conducted to describe and analyze the results of the review. Outcomes were summarized using the mean difference or standardized mean difference where appropriate. The search produced 1,816 records. Six studies met the inclusion criteria (five individually RCTs and one cluster RCT). Four studies reported data on all three STH species, while one study only reported data on Ascaris lumbricoides infections and the last study reported data on only hookworm infections. Overall, the risk of bias in four individual studies was low across most domains. Nutritional supplementation failed to statistically reduce the re-infection rates of the three STH species. The effect of nutritional supplements on measures of physical wellbeing in school-aged children could not be determined. The findings from this systematic review suggest that nutritional supplements for treatment of STH in children should not be encouraged unless better evidence emerges. Conclusion of earlier reviews on general populations may not necessarily apply to children since children possibly have a higher re-infection rate.