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Survey of Ophthalmology 2022Pars plana vitrectomy (PPV) and scleral buckling (SB) are two of the most common surgical treatments for rhegmatogenous retinal detachment (RRD). This meta-analysis... (Meta-Analysis)
Meta-Analysis Review
Pars plana vitrectomy (PPV) and scleral buckling (SB) are two of the most common surgical treatments for rhegmatogenous retinal detachment (RRD). This meta-analysis compares the efficacy and safety of PPV and SB for RRD. A systematic literature review was performed using Ovid MEDLINE, EMBASE and Cochrane CENTRAL from 2000 to June, 2021. Comparative studies, randomized controlled trials and observational studies investigating PPV and SB for RRD repair were included. The primary endpoint was final best- corrected visual acuity (BCVA). Secondary endpoints were reattachment rates, total operation time, and incidence of adverse events. Subgroup analyses including phakic status, presence of PVR-C or greater at baseline, and macular attachment status were conducted. Across 41 studies (8 RCTs, 33 observational studies), 5,401 SB and 10,546 PPV eyes were included. SB achieved a statistically significant, but likely not clinically significant, better final BCVA than PPV (0.38 ± 0.53 vs. 0.33 ± 0.53 logMAR (20/48 vs. 20/43 Snellen); weighted mean difference [WMD]: 0.07; 95% confidence interval: [0.02-0.11]; P = 0.005). SB had a better final BCVA compared to PPV in observational studies (P = 0.007) but not in RCTs (P = 0.21). SB had a lower incidence of post-operative cataract formation (P < 0.00001) and iatrogenic breaks (P < 0.00001), but a higher incidence of choroidal/subretinal hemorrhage (P = 0.007), choroidal detachment (P = 0.004), and residual subretinal fluid (RSRF) (P < 0.00001). Primary (86.5% vs. 84.8%; P = 0.13) and final (96.7% vs. 97.7%; P = 0.12) reattachment rates were similar between PPV and SB. PPV had a significantly higher primary reattachment rate in RCTs (P = 0.02) but not in observational studies (P = 0.30). SB was associated with a better final BCVA than PPV; however, this result was primarily driven by observational studies and phakic patients who developed cataracts. Primary and final reattachment rates were similar between the comparators. SB was associated with a significantly lower incidence of iatrogenic breaks and cataracts, while PPV was associated with a reduced risk of choroidal detachment, subretinal hemorrhage, and RSRF.
Topics: Cataract; Choroidal Effusions; Hemorrhage; Humans; Iatrogenic Disease; Retinal Detachment; Retrospective Studies; Scleral Buckling; Treatment Outcome; Vitrectomy
PubMed: 34896191
DOI: 10.1016/j.survophthal.2021.12.005 -
Cancer Treatment Reviews Nov 2023To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis. (Review)
Review
BACKGROUND/OBJECTIVE
To analyze changes in recurrent/refractory osteosarcoma phase II trials over time to inform future trials in this population with poor prognosis.
METHODS
A systematic review of trials registered on trial registries between 01/01/2017-14/02/2022. Comparison of 98 trials identified between 2003 and 2016. Publication search/analysis for both periods, last update on 01/12/2022.
RESULTS
Between 2017 and 2022, 71 phase-II trials met our selection criteria (19 osteosarcoma-specific trials, 14 solid tumor trials with and 38 trials without an osteosarcoma-specific stratum). The trial number increased over time: 13.9 versus 7 trials/year (p = 0.06). Monotherapy remained the predominant treatment (62% vs. 62%, p = 1). Targeted therapies were increasingly evaluated (66% vs. 41%, P = 0.001). Heterogeneity persisted in the trial characteristics. The inclusion criteria were measurable disease (75%), evaluable disease (14%), and surgical remission (11%). 82% of the trials included pediatric or adolescent patients. Biomarker-driven trials accounted for 25% of the total trials. The survival endpoint use (rather than response) slightly increased (40% versus 31%), but the study H/H hypotheses remained heterogeneous. Single-arm designs predominated over multiarm trials (n = 7). Available efficacy data on 1361 osteosarcoma patients in 58 trials remained disappointing, even though 21% of these trials were considered positive, predominantly those evaluating multi-targeted kinase inhibitors.
CONCLUSION
Despite observed changes in trial design and an increased number of trials investigating new therapies, high heterogeneity remained with respect to patient selection, study design, primary endpoints, and statistical hypotheses in recently registered phase II trials for osteosarcoma. Continued optimization of trial design informed by a deeper biological understanding should strengthen the development of new therapies.
PubMed: 37738712
DOI: 10.1016/j.ctrv.2023.102625 -
Journal of Cachexia, Sarcopenia and... Oct 2023In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function...
In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.
Topics: Humans; Cachexia; Hand Strength; Neoplasms; Quality of Life; Research Design
PubMed: 37671529
DOI: 10.1002/jcsm.13321 -
BJOG : An International Journal of... Sep 2016Heavy menstrual bleeding (HMB) is a common problem with a variety of treatment options and many studies have been performed evaluating treatment effects. Consistency in... (Review)
Review
BACKGROUND
Heavy menstrual bleeding (HMB) is a common problem with a variety of treatment options and many studies have been performed evaluating treatment effects. Consistency in the choice and definition of primary and secondary outcomes is important for the interpretation of data and for the synthesis of data in systematic reviews or individual patient data meta-analysis (IPDMA).
OBJECTIVE
To give insight into the primary endpoints and outcome measures chosen in randomised controlled trials (RCTs) and systematic reviews regarding the treatment of HMB.
SEARCH STRATEGY
Published systematic reviews and RCTs.
SELECTION CRITERIA
Full reports of RCTs or systematic reviews.
DATA COLLECTION AND ANALYSIS
For RCTs, we used the primary outcomes, as they were used for the sample size calculation. For systematic reviews, all outcomes listed as primary were included. Four authors selected the studies.
RESULTS
Twelve different primary outcomes were reported by 66 RCTs, most blood loss- related (44/66 studies). Amenorrhoea was the most common blood loss primary outcome (16/44 studies) and the Pictorial Blood Loss Assessment Chart (PBAC) was the most used measurement tool (27/44 studies). Satisfaction was the second most prevalent primary outcome measure (13/66 studies). In all, 14/26 (54%) systematic reviews prespecified a single primary outcome, whereas all other reviews used composite primary outcomes. Blood loss was the most studied outcome (12/26 reviews).
CONCLUSIONS
The most used primary outcomes in HMB studies relate to blood loss but there is no consistency regarding the endpoints chosen or measurement tools used to describe blood loss. Standardising outcomes will aid valid comparison and interpretation of data pertaining to the treatment of HMB.
TWEETABLE ABSTRACT
A standardised collection of outcomes in heavy menstrual bleeding research is urgently needed.
Topics: Amenorrhea; Evidence-Based Medicine; Female; Humans; Menorrhagia; Meta-Analysis as Topic; Randomized Controlled Trials as Topic
PubMed: 27240106
DOI: 10.1111/1471-0528.14054 -
Journal of Crohn's & Colitis Jun 2024Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our...
BACKGROUND
Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries.
METHODS
Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded.
RESULTS
In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications.
CONCLUSIONS
Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.
Topics: Crohn Disease; Humans; Recurrence; Ileum
PubMed: 38112601
DOI: 10.1093/ecco-jcc/jjad205 -
Pediatric Cardiology Feb 2023Sample size and statistical power are often limited in pediatric cardiology studies due to the relative infrequency of specific congenital malformations of the heart and... (Review)
Review
Sample size and statistical power are often limited in pediatric cardiology studies due to the relative infrequency of specific congenital malformations of the heart and specific circulatory physiologies. The primary aim of this study was to determine what proportion of pediatric cardiology randomized controlled trials achieve an 80% statistical power. Secondary aims included characterizing reporting habits in these studies. A systematic review was performed to identify pertinent pediatric cardiology randomized controlled trials. The following data were collected: publication year, journal, if "power" or "sample size" were mentioned if a discrete, primary endpoint was identified. Power analyses were conducted to assess if the sample size was adequate to demonstrate results at 80% power with a p-value of less than 0.05. A total of 83 pediatric cardiology randomized controlled trials were included. Of these studies, 48% mentioned "power" or "sample size" in the methods, 49% mentioned either in the results, 12% mentioned either in the discussion, and 66% mentioned either at any point in the manuscript. 63% defined a discrete, primary endpoint. 38 studies (45%) had an adequate sample size to demonstrate differences with 80% power at a p-value of less than 0.05. A majority of these are not powered to reach the conventionally accepted 80% power target. Adequately powered studies were found to be more likely to report "power" or "sample size" and have a discrete, primary endpoint.
Topics: Humans; Child; Randomized Controlled Trials as Topic; Cardiology; Sample Size
PubMed: 36324012
DOI: 10.1007/s00246-022-03039-z -
Minerva Endocrinologica Mar 2017Long-term outcome of patients with adrenal incidentaloma (AI) is unknown. The aim of this study was to systematically summarize the follow-up and outcome of clinically... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Long-term outcome of patients with adrenal incidentaloma (AI) is unknown. The aim of this study was to systematically summarize the follow-up and outcome of clinically silent AI who do not undergo surgery.
EVIDENCE ACQUISITION
All major databases and medical literature in English-language, published from 1998 to May 2015, were systematically searched for publications on AI. Primary endpoint was hormonal hyper function; secondary endpoints were time from diagnosis to study endpoint and the outcome of adrenalectomy. Meta-analysis was performed using both qualitative and quantitative approach.
EVIDENCE SYNTHESIS
A total of 11 publications were included. Total sample size was 1298 patients. Mean follow-up duration was 44.2 months. There were 82 patients confirmed to have subclinical Cushing's syndrome at diagnosis, with 1.79% new cases at the end of follow up (95% CI, 0.002 to 0.045). Incidence of Cushing's syndrome was 0.7% (95% CI, 0.001 to 0.013) and pheochromocytoma 0.4% (95% CI, 0.001 to 0.008). The mean tumor size was 2.52cm, with mean increment of 0.03cm to 2.9cm at the end of follow up. About 3% of patients ended up with surgery (95% CI, 0.01 to 0.05) but none were due to primary adrenal malignancy. Time of greatest risk of developing Cushing's syndrome and pheochromocytoma was between months 36 and 42 (hazard rate 14%), and between months 48 and 54 (hazard rate 7%) respectively.
CONCLUSIONS
Malignant change in non-functioning AI is rare. The risk of developing overt disease over the follow-up period is low. A less stringent imaging and functional work-up interval can be considered.
Topics: Adrenal Gland Neoplasms; Disease Progression; Humans; Treatment Outcome
PubMed: 26698544
DOI: 10.23736/S0391-1977.16.02394-4 -
Heart, Lung & Circulation Sep 2023Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We... (Review)
Review
BACKGROUND
Current pharmacological options for hypertrophic cardiomyopathy (HCM) are not disease-specific; while it treats symptoms, mavacamten targets the underlying pathology. We aim to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive HCM.
METHODS
This systematic review of the literature followed the PRISMA guidelines. Title/abstract and topics were searched using the following term: "mavacamten". The electronic research literature databases included the Cochrane Library, MedLine, and clinicaltrials.gov from July to August 2022. Primary efficacy endpoint was to assess clinical response at the end of treatment compared with baseline, defined as, at least one New York Heart Association (NYHA) class reduction. Two secondary endpoints from baseline were determined. The first was defined as improvement in mixed venous oxygen pressure (pVO). The second was defined as reduction of the post-exercise left ventricular outflow tract (LVOT) gradient.
RESULTS
We included in our analyses data from four studies that met our review eligibility criteria. There were three randomised placebo-controlled clinical trials and one non-randomised open-label clinical trial. All four studies showed a reduction in NYHA class from mavacamten use. Three out of four studies demonstrated >1 NYHA functional class improvement ranging from 34% to 80%, while only one study showed a smaller percentage of patients remaining at class 3. Three out of four studies measured pVO as an outcome, and all three studies noticed an increase in peak oxygen consumption after mavacamten treatment. Additionally, three out of four studies measured post-exercise LVOT gradient reduction as an outcome and all three found significant reduction in the post-exercise LVOT gradient after treatment. The most commonly observed adverse side effects were atrial fibrillation and decreased left ventricular ejection fraction, but all participants recovered without long-term sequelae and only one patient dropped out of the trial.
CONCLUSIONS
Mavacamten has a greater efficacy than placebo in the treatment of HCM. It also showed promising tolerability and efficacy profiles in the treatment of HCM in adults. The three endpoints used in the evaluation of studies were reduction in NYHA class, increase in pVO, and post-exercise LVOT gradient reduction. Mavacamten showed greater reduction in NYHA, larger effects on increase of pVO, and significant reduction of the LVOT gradient. Mavacamten was also found to be well tolerated, like the placebo. The side effect profile was limited for the majority of individuals taking mavacamten. In the future, authors recommended dose-optimisation studies, and studies that evaluate mavacamten both in comparison to, and in conjunction with other current treatments.
Topics: Adult; Humans; Cardiomyopathy, Hypertrophic; Heart; Stroke Volume; Ventricular Function, Left; Clinical Trials as Topic
PubMed: 37453852
DOI: 10.1016/j.hlc.2023.05.019 -
European Urology Oct 2023In the oncology setting, patient-reported outcome measures (PROMs) provide important data that help to ensure patient-relevant endpoints are captured and reported. Use... (Review)
Review
CONTEXT
In the oncology setting, patient-reported outcome measures (PROMs) provide important data that help to ensure patient-relevant endpoints are captured and reported. Use of this information for treatment decision-making by clinicians and patients in real-world settings is facilitated by consistent and transparent reporting of trial methods.
OBJECTIVE
To identify and compare PROMs used in advanced renal cell carcinoma (RCC) trials in terms of the rationale for the choice of measure, endpoint hierarchy (primary, secondary, exploratory), assessment time points, statistical methods, and statistical metrics for interpretation.
EVIDENCE ACQUISITION
A systematic literature review via searches of four online databases (2016-2021) and recent conference abstracts (2019-2021) identified 2616 articles, of which 33 were included in the review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
EVIDENCE SYNTHESIS
Among the 33 clinical studies included, 19 different PROMs were identified: three kidney cancer-specific scales, two cancer-specific scales, two generic scales, and 12 symptom-specific scales. The endpoint hierarchy for patient reported outcome (PRO) assessment was reported in 42% of the studies; one study included PROs as a primary endpoint. Reporting of time points, minimal important differences, and statistical analyses was highly heterogeneous.
CONCLUSIONS
A diverse range of PROMs have been included in clinical studies for patients with advanced/metastatic RCC. Prespecified analyses for PRO assessments were generally not stated, while analytical methods and reporting varied. An improvement in alignment across studies would better inform regulatory, market-access, reimbursement, and clinical decision-making to improve patient care.
PATIENT SUMMARY
We reviewed how the impact of cancer therapies on health outcomes from the patient's point of view is being measured in clinical trials for kidney cancer. The techniques and reporting varied across trials. Standardisation of how these data are captured and reported may improve care and decision-making for patients with kidney cancer.
Topics: Humans; Carcinoma, Renal Cell; Patient Reported Outcome Measures; Kidney Neoplasms; Patient Outcome Assessment; Research Design
PubMed: 37550153
DOI: 10.1016/j.eururo.2023.07.006 -
PloS One 2017Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct... (Meta-Analysis)
Meta-Analysis Review
Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct cardiovascular protective properties have therefore been proposed, and studied in preclinical models of myocardial infarction. We now aim to critically assess the quality and outcome of these studies. We present a systematic review, quality assessment and meta-analysis of the effect of metformin in animal studies of experimental myocardial infarction. Through a comprehensive search in Pubmed and EMBASE, we identified 27 studies, 11 reporting on ex vivo experiments and 18 reporting on in vivo experiments. The primary endpoint infarct size as percentage of area at risk was significantly reduced by metformin in vivo (MD -18.11[-24.09,-12.14]) and ex vivo (MD -18.70[-25.39, -12.02]). Metformin improved the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter. A borderline significant effect on mortality was observed, and there was no overall effect on cardiac hypertrophy. Subgroup analyses could be performed for comorbidity and timing of treatment (infarct size and mortality) and species and duration of ischemia (LVEF), but none of these variables accounted for significant amounts of heterogeneity. Reporting of possible sources of bias was extremely poor, including randomization (reported in 63%), blinding (33%), and sample size calculation (0%). As a result, risk of bias (assessed using SYRCLE's risk of bias tool) was unclear in the vast majority of studies. We conclude that metformin limits infarct-size and improves cardiac function in animal models of myocardial infarction, but our confidence in the evidence is lowered by the unclear risk of bias and residual unexplained heterogeneity. We recommend an adequately powered, high quality confirmatory animal study to precede a randomized controlled trial of acute administration of metformin in patients undergoing reperfusion for acute myocardial infarction.
Topics: Animals; In Vitro Techniques; Metformin; Mice; Myocardial Infarction; Rabbits; Rats; Swine
PubMed: 28832637
DOI: 10.1371/journal.pone.0183664