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Supportive Care in Cancer : Official... Jun 2017Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial... (Review)
Review
PURPOSE
Clinical trials in radiation therapy-induced nausea and vomiting (RINV) appear to have varied methodologies, endpoints, and outcome measures. This complicates trial comparisons, weakens practice guideline recommendations, and contributes to variability in supportive care patterns of practice. We systematically reviewed RINV trials to describe and compare their pertinent design features.
MATERIALS AND METHODS
Ovid versions of the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, EMBASE, and MEDLINE to January/February 2017 were searched for adult phase III trials of RINV management strategies. Key abstracted data included trial interventions and eligibility criteria, standard radiation therapy (RT) metrics, symptom assessment procedures, symptom definitions and grading systems, pre-specified and reported endpoints, and other outcome measures.
RESULTS
From 1166 references identified in the initial database search, we selected 34 trials for analysis that collectively randomized 4529 patients (median 61, range 11-1492). Twenty-eight trials (82%) were published prior to the year 2000. Twenty-seven trials (79%) involved multiple fraction RT and 7 (21%) single fraction RT. Twenty-four trials (71%) evaluated prophylactic interventions, 9 (26%) rescue interventions, and 1 trial did not specify. Thirty-three trials (97%) evaluated pharmacologic interventions. Twenty trials (59%) had patient report symptoms, 5 (15%) healthcare professionals or researchers, and 10 (29%) did not specify. Nausea was not defined in any trial but was reported as a stand-alone symptom in 26 trials (76%) and was graded in 20 (59%), with categorical qualitative scales being the most common method. Vomiting was defined in 3 trials (9%), was reported as a stand-alone symptom in 17 (47%), and was graded in 7 (21%), with continuous numerical scales being the most common method. Retching was defined in 3 trials, was not reported as a stand-alone symptom in any trial, and was graded in 1 (3%). Twenty-one trials (62%) created compound symptom measures that combined individual symptoms. Fifteen trials (44%) reported "emetic episode/event" measures but only 9 defined them. Seventeen trials (50%) reported complicated endpoints (e.g., "response," "control," "success") that combined multiple symptom or compound symptom measures, but 7 did not define them comprehensively. Ten trials (29%) defined a primary endpoint a priori.
CONCLUSIONS
Methodologies, endpoints, and outcome measures varied considerably among 34 randomized trials in RINV.
Topics: Adult; Antiemetics; Humans; Nausea; Outcome Assessment, Health Care; Radiotherapy; Randomized Controlled Trials as Topic; Vomiting
PubMed: 28364173
DOI: 10.1007/s00520-017-3685-9 -
PloS One 2017This systematic review and meta-analysis aims to assess the therapeutic and adverse effects of acupuncture for benign prostatic hyperplasia (BPH) in randomized... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This systematic review and meta-analysis aims to assess the therapeutic and adverse effects of acupuncture for benign prostatic hyperplasia (BPH) in randomized controlled trials (RCTs).
METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, the Chinese Biomedical Database, the China National Knowledge Infrastructure, the VIP Database and the Wanfang Database. Parallel-group RCTs of acupuncture for men with symptomatic BPH were included. Data from the included trials were extracted by two independent reviewers and were analyzed with The Cochrane Collaboration Review Manager software (RevMan 5.3.5) after risk of bias judgments. The primary outcome measure of this review was a change in urological symptoms.
RESULTS
Eight RCTs, which involved 661 men with BPH, were included. Follow-up varied from 4 weeks to 18 months. Pooling of the data from three trials that compared acupuncture with sham-acupuncture revealed that in the short term (4-6 weeks), acupuncture can significantly improve IPSS (MD -1.90, 95% CI -3.58 to -0.21). A sensitivity analysis of the short-term endpoint showed the same result (MD -3.01, 95% CI -5.19 to -0.84) with a borderline minimal clinical important difference (MCID). Qmax of the short-term endpoint indicated statistically positive beneficial effects of acupuncture (MD -1.78, 95%CI -3.43, -0.14). A meta-analysis after medium-term follow-up (12-18 weeks) indicated no significant effect on IPSS when the data from two trials were combined (MD -2.04, 95% CI -4.19, 0.10).
CONCLUSION
Statistically significant changes were observed in favor of acupuncture in moderate to severe BPH with respect to short-term follow-up endpoints. The clinical significance of these changes needs to be tested by further studies with rigorous designs and longer follow-up times.
TRIAL REGISTRATION NUMBER
PROSPERO CRD42014013645.
Topics: Acupuncture Therapy; Humans; Male; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28376120
DOI: 10.1371/journal.pone.0174586 -
Frontiers in Pharmacology 2022Systematic comparison of the efficacy and safety of nebulized corticosteroids and systemic corticosteroids for treating acute exacerbation of chronic obstructive... (Review)
Review
Nebulized corticosteroids systemic corticosteroids for patients with acute exacerbation of chronic obstructive pulmonary disease: A systematic review and meta-analysis comparing the benefits and harms reported by observational studies and randomized controlled trials.
Systematic comparison of the efficacy and safety of nebulized corticosteroids and systemic corticosteroids for treating acute exacerbation of chronic obstructive pulmonary disease reported by high-quality, real-world observational studies and randomized controlled trials. MEDLINE, EMBASE, and Cochrane Library databases were searched from the database creation date to 1 April 2022. Eligible observational studies and randomized controlled trials with changes in lung function and blood gas analysis results as the primary endpoints of interest, and the numbers of deteriorations and adverse events as the secondary endpoints were sought. Of the 2,837 identified studies, 22 were eligible and included in our analysis (N = 5,764 patients). Compared with systemic corticosteroids, nebulized corticosteroids resulted in comparable improvements in predicted FEV%, FEV, PaO, PaCO, and SaO at the treatment endpoint; however, observational studies reported more significant treatment outcomes with nebulized corticosteroids for FEV [mean difference, 0.26; 95% confidence interval (CI), 0.17-0.35; < 0.005]. In terms of adverse reactions, the risks of gastrointestinal symptoms were 11% [Log risk ratio (LogRR) = 0.10; 95% confidence interval, 0.05-0.15; < 0.005] higher for systemic corticosteroids than for nebulized corticosteroids in randomized controlled trials, while the risks of hyperglycemia were 6% (LogRR = 0.06; 95% CI, 0.01-0.11; = 0.01) and 13% (LogRR = 0.12; 95% CI, 0.09-0.16; < 0.005) higher in observational studies and randomized controlled trials, respectively. According to our meta-analysis, either study type supported that nebulized corticosteroids can be used as an alternative to systemic corticosteroids for treating acute exacerbation of the chronic obstructive pulmonary disease. However, more well-designed prospective studies are needed to determine the optimal dose of nebulized corticosteroids and the advantages of sequential therapy.
PubMed: 36278148
DOI: 10.3389/fphar.2022.966637 -
Movement Disorders : Official Journal... Dec 2013Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these... (Meta-Analysis)
Meta-Analysis Review
Treatment effect in Huntington disease (HD) clinical trials has relied on primary outcome measures such as total motor score or functional rating scales. However, these measures have limited sensitivity, particularly in pre- to early stages of the disease. We performed a systematic review of HD clinical studies to identify endpoints that correlate with disease severity. Using standard HD keywords and terms, we identified 749 published studies from 1993 to 2011 based on the availability of demographic, biochemical, and clinical measures. The average and variability of each measure was abstracted and stratified according to pre-far, pre-close, early, mild, moderate, and severe HD stages. A fixed-effect meta-analysis on selected variables was conducted at various disease stages. A total of 1,801 different clinical variables and treatment outcomes were identified. Unified Huntington Disease Rating Scale (UHDRS) Motor, UHDRS Independence, and Trail B showed a trend toward separation between HD stages. Other measures, such as UHDRS Apathy, Verbal Fluency, and Symbol Digit, could only distinguish between pre- and early stages of disease and later stages, whereas other measures showed little correlation with increasing HD stages. Using cross-sectional data from published HD clinical trials, we have identified potential endpoints that could be used to track HD disease progression and treatment effect. Longitudinal studies, such as TRACK-HD, are critical for assessing the value of potential markers of disease progression for use in future HD therapeutic trials. A list of variables, references used in this meta-analysis, and database is available at http://www.cmmt.ubc.ca/research/investigators/leavitt/publications.
Topics: Biomedical Research; Databases, Bibliographic; Humans; Huntington Disease
PubMed: 24142393
DOI: 10.1002/mds.25663 -
European Journal of Anaesthesiology Sep 2023Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. (Meta-Analysis)
Meta-Analysis
The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.
BACKGROUND
Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.
OBJECTIVES
To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.
DESIGN
A systematic review and meta-analysis with trial sequential analysis.
DATA SOURCES
MEDLINE, Embase and Web of Science, among others, up to June 2022.
ELIGIBILITY CRITERIA
We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.
RESULTS
Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P = 0.15), 48 h ( P = 0.15) and 72 h ( P = 0.07). The quality of evidence was moderate.
CONCLUSIONS
There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.
Topics: Humans; Anesthetics, Local; Pain, Postoperative; Bupivacaine; Analgesics; Morphine; Peripheral Nerves; Analgesics, Opioid
PubMed: 37038770
DOI: 10.1097/EJA.0000000000001833 -
Journal of Cardiothoracic and Vascular... Apr 2017Postoperative pulmonary complications (PPC) are among the most common complications after noncardiac surgery. Men, smokers, and elderly patients with chronic obstructive... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Postoperative pulmonary complications (PPC) are among the most common complications after noncardiac surgery. Men, smokers, and elderly patients with chronic obstructive pulmonary disease or heart failure are more likely to experience PPC. The majority of patients undergoing vascular surgery belong in these categories and are at higher risk of developing PPC. Moreover, the surgical site is one of the most important risk factors associated with PPC, and aortic surgery carries the highest risk. The aim of this systematic review was to obtain an additional understanding of the real incidence of PPC after open abdominal aortic surgery and the impact of PPC on survival.
DESIGN
Systematic review and meta-analysis.
SETTING
Hospitals PARTICIPANTS: Patients who underwent open abdominal aortic surgery.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A literature search was performed on BioMedCentral, PubMed, Embase, and the Cochrane Register of clinical trials. All prospective or retrospective studies reporting data on PPC after open abdominal aortic surgery were included. Co-primary endpoints were the PPC rate and the correlation between PPC and perioperative mortality. The secondary endpoint was the difference in the PPC rate and mortality between elective and urgent surgery. Data on 269,637 patients from 213 studies were analyzed. The overall median incidence of PPC was 10.3% (interquartile range 5.55%-19.1%). Pneumonia, respiratory insufficiency, prolonged mechanical ventilation, need for unplanned mechanical ventilation, atelectasis, acute respiratory distress syndrome, pulmonary edema, and pleural effusions were the most common PPC reported in the literature. Occurrence of PPC was associated with postoperative mortality (r = 0.65, p<0.01) and was significantly higher in urgent procedures (p<0.001).
CONCLUSIONS
Incidence of PPC after open abdominal aortic surgery is high and is associated with increased postoperative morbidity and mortality.
Topics: Aorta, Abdominal; Humans; Postoperative Complications; Prospective Studies; Respiration Disorders; Respiratory Insufficiency; Retrospective Studies
PubMed: 27988091
DOI: 10.1053/j.jvca.2016.09.034 -
International Journal of Surgery... Aug 2022In the modern era, minimally invasive surgery is rapidly evolving and even replacing conventional open techniques in many surgical fields. Thyroidectomy was not an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In the modern era, minimally invasive surgery is rapidly evolving and even replacing conventional open techniques in many surgical fields. Thyroidectomy was not an exception, with the introduction of multiple endoscopic thyroidectomy techniques. Trans-oral endoscopic trans-vestibular thyroidectomy (TOT) is a novel technique with promising outcomes. We conducted this meta-analysis to compare surgical outcomes and learning curves for TOT and other endoscopic thyroidectomy techniques.
METHODS
A systematic review in PubMed, MEDLINE, and EMBASE databases was conducted searching for publications on TOT versus trans-axillary thyroidectomy (TAT). The primary endpoint was operative (OR) time. Secondary endpoints were number of harvested lymph nodes (LNs), estimated blood loss (EBL), recurrent laryngeal nerve (RLN) injury, hoarseness, seroma, infection, chyle leak, hypocalcemia, hospital length of stay (LOS), and Cost. We also investigated the learning curve for each technique. Leave-out-out analysis, meta-regression, and subgroup analysis were used. Random effect inverse variance method was utilized.
RESULTS
Among 3820 retrieved studies, 15 studies (10 unmatched and 5 matched), with 2173 (TOT: 1024(47.12%) and TAT:1149(52.87%)) patients, met the inclusion criteria. The operative time and harvested L. Ns number were higher in TOT versus TAT (standard mean difference (SMD) = 0.72 [95%CI 0.07; 1.37], P = 0.029 and SMD = 0.32 [95%CI 0.02; 0.62], P = 0.036 respectively) while less EBL in TOT versus TAT (SMD = -0.26 [-0.43; -0.09], P = 0.0018). All other outcomes showed no significant difference between both groups. Weighted mean values for TOT and TAT were 158.03 vs 144.97 min for OR time, 6.33 vs 5.16 for harvested LNs, and $5,919.05 vs $6,253.79 for the cost. Statistical significance in learning curve development was noticed ranging between 6 and 15 annual cases.
CONCLUSION
Trans-oral thyroidectomy is a safe and reliable technique with outcomes comparable to other endoscopic techniques. It provides better access to the central compartment with a more feasible LN dissection. Improvement in surgical outcomes is expected with growing learning curve and technique mastery.
Topics: Axilla; Endoscopy; Humans; Learning Curve; Operative Time; Thyroid Neoplasms; Thyroidectomy
PubMed: 35764254
DOI: 10.1016/j.ijsu.2022.106739 -
European Urology Focus Jan 2024Symptomatic lymphocele (sLC) occurs at a frequency of 2-10% after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). Construction of... (Meta-Analysis)
Meta-Analysis Review
Impact of Peritoneal Interposition Flap on Patients Undergoing Robot-assisted Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
CONTEXT
Symptomatic lymphocele (sLC) occurs at a frequency of 2-10% after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). Construction of bilateral peritoneal interposition flaps (PIFs) subsequent to completion of RARP + PLND has been introduced to reduce the risk of lymphocele, and was initially evaluated on the basis of retrospective studies.
OBJECTIVE
To conduct a systematic review and meta-analysis of only randomized controlled trials (RCTs) evaluating the impact of PIF on the rate of sLC (primary endpoint) and of overall lymphocele (oLC) and Clavien-Dindo grade ≥3 complications (secondary endpoints) to provide the best available evidence.
EVIDENCE ACQUISITION
In accordance with the Preferred Reporting Items for Meta-Analyses statement for observational studies in epidemiology, a systematic literature search using the MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE databases up to February 3, 2023 was performed to identify RCTs. The risk of bias (RoB) was assessed using the revised Cochrane RoB tool for randomized trials. Meta-analysis used random-effect models to examine the impact of PIF on the primary and secondary endpoints.
EVIDENCE SYNTHESIS
Four RCTs comparing outcomes for patients undergoing RARP + PLND with or without PIF were identified: PIANOFORTE, PerFix, ProLy, and PLUS. PIF was associated with odds ratios of 0.46 (95% confidence interval [CI] 0.23-0.93) for sLC, 0.51 (95% CI 0.38-0.68) for oLC, and 0.41 (95% CI 0.21-0.83) for Clavien-Dindo grade ≥3 complications. Functional impairment resulting from PIF construction was not observed. Heterogeneity was low to moderate, and RoB was low.
CONCLUSIONS
PIF should be performed in patients undergoing RARP and simultaneous PLND to prevent or reduce postoperative sLC.
PATIENT SUMMARY
A significant proportion of patients undergoing prostate cancer surgery have regional lymph nodes removed. This part of the surgery is associated with a risk of postoperative lymph collections (lymphocele). The risk of lymphocele can be halved via a complication-free surgical modification called a peritoneal interposition flap.
Topics: Male; Humans; Robotics; Lymphocele; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Lymph Node Excision; Prostatectomy
PubMed: 37541915
DOI: 10.1016/j.euf.2023.07.007 -
Critical Care (London, England) Jun 2017Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) are often selected for randomized clinical trials (RCTs) aiming at new drug approval. Guidelines for the... (Review)
Review
BACKGROUND
Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) are often selected for randomized clinical trials (RCTs) aiming at new drug approval. Guidelines for the design of such RCTs have been repeatedly updated by regulatory agencies. We hypothesized that large variability in the enrolled populations, the endpoints assessed and the HAP/VAP definition criteria may impact the results of these studies, and addressed this through a systematic review of HAP/VAP RCTs.
METHODS
A search (Pubmed-Embase-ICAAC-ECCMID) of all RCTs published between 1994 and 2016 comparing antimicrobial treatment for HAP/VAP in the intensive care unit was conducted. The populations enrolled, inclusion/exclusion criteria, statistical design and endpoints assessed were recorded. All unpublished RCTs recorded on the ClinicalTrials.gov registry were also screened.
RESULTS
From the 93 abstracts reviewed, 39 potentially relevant studies were inspected, leading to 27 studies being included. As expected, illness severity or the proportion with VAP (27-100%) differed greatly among the enrolled populations. The HAP/VAP definition used various clinical and biological criteria, and only 55% of studies required a microbiological sample. The mandatory duration of prior hospital stay was variable; the mechanical ventilation duration was an inclusion criterion in only 41% of VAP studies. Nine studies had non-inferiority design, but nine studies (33%) did not have a pre-specified statistical hypothesis. Clinical cure was the primary endpoint in 24 studies, but was recorded in several populations or as the co-primary endpoint in 13 studies. The definition of clinical cure and the timing of its assessment greatly differed. This variability slightly improved over time but remained significant in the 13 registered but currently unpublished RCTs that we screened.
CONCLUSION
Our study provides a description of populations and endpoints of RCTs evaluating antimicrobials for treatment of HAP/VAP in the ICU. There was significant heterogeneity in enrollment criteria, endpoints and statistical design, which may influence the ability of studies to demonstrate differences between studied drugs.
Topics: Anti-Bacterial Agents; Cross Infection; Humans; Intensive Care Units; Pneumonia, Ventilator-Associated; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 28655326
DOI: 10.1186/s13054-017-1755-5 -
Journal of Neurosurgery. Pediatrics Sep 2019The optimal revascularization for pediatric moyamoya for reducing the incidence of future stroke events remains to be determined. (Review)
Review
OBJECTIVE
The optimal revascularization for pediatric moyamoya for reducing the incidence of future stroke events remains to be determined.
METHODS
The authors conducted a search of PubMed, MEDLINE, Embase, and Web of Science electronic databases from inception until January 2019. The primary endpoint was the presence of a future ischemic stroke event. Secondary endpoints were angiographic outcomes as measured by postoperative Matsushima grade and clinical symptom persistence. Patients who underwent either direct or combined direct/indirect revascularization were classified into the direct cohort. Data from each study on presence of postoperative stroke events were used to generate standardized mean differences and 95% confidence intervals, which were combined using inverse variance-weighted averages of standardized mean differences in a random effects model.
RESULTS
Twenty-nine studies met the inclusion criteria for analysis, comprising 2258 patients (1011 males, mean age 8.3 ± 1.8 years) who were followed up clinically for an average of 71.4 ± 51.3 months. One hundred fifty-four patients underwent direct bypass alone, 680 patients underwent either direct or combined direct/indirect revascularization procedures, while 1424 patients underwent indirect bypass alone. The frequencies of future stroke events in patients undergoing direct bypass alone, combined bypass, or indirect bypass alone were 1 per 190.3 patient-years, 1 per 108.9 patient-years, and 1 per 61.1 patient-years, respectively, in each cohort. The estimated stroke rates were 9.0% with indirect revascularization, 4.5% with direct revascularization alone, and 6.0% with combined revascularization. A forest plot did not reveal any significant differences in the incidence of future stroke events or angiographic outcomes following direct-only, combined, or indirect-only revascularization.
CONCLUSIONS
Direct, indirect, and combined indirect/direct bypass techniques are all effective revascularization options for pediatric moyamoya disease. A relative paucity of granular studies-and inherent surgical selection bias-limits direct comparison between interventions. Suitably designed prospective cohort studies may be useful in identifying patients likely to receive benefit from specific procedures.
PubMed: 31518973
DOI: 10.3171/2019.6.PEDS19241