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International Journal of Colorectal... Jan 2022The laparoscopic approach in the treatment of mid- or low-rectal cancer is still controversial. Compared with open surgery, laparoscopic resection of extraperitoneal... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The laparoscopic approach in the treatment of mid- or low-rectal cancer is still controversial. Compared with open surgery, laparoscopic resection of extraperitoneal cancer is associated with improved short-time non-oncological outcomes, although high-level evidence showing similar short- and long-term oncological outcomes is scarce.
OBJECTIVE
The aim of our paper is to study the oncological and non-oncological outcomes of laparoscopic versus open surgery for extraperitoneal rectal cancer.
DATA SOURCES
A systematic review of MedLine, EMBASE, and CENTRAL from January 1990 to October 2020 was performed by combining various key words.
STUDY SELECTION
Only randomized controlled trials (RCTs) comparing laparoscopic versus open surgery for extraperitoneal rectal cancer were included. The quality of RCTs was assessed using the Cochrane reviewer's handbook. This meta-analysis was based on the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.
INTERVENTION(S)
This study analyzes laparoscopic versus open surgery for extraperitoneal rectal cancer.
MAIN OUTCOME MEASURES
Primary outcomes were oncological parameters.
RESULTS
Fifteen RCTs comprising 4,411 patients matched the selection criteria. Meta-analysis showed a significant difference between laparoscopic and open surgery in short-time non-oncological outcomes. Although laparoscopic approach increased operation time, it decreases significantly the blood loss and length of hospital stay. No significant difference was noted regarding short- and long-term oncological outcomes, but 4 and 5 years disease-free survival were statistically higher in the open group.
LIMITATIONS
There are still questions about the long-term oncological outcomes of laparoscopic surgery for extraperitoneal rectal cancer being comparable to the open technique.
CONCLUSIONS
Considering that all surgical resections have been performed in high volume centers by expert surgeons, the minimally invasive surgery in patients with extraperitoneal cancer could still be not considered equivalent to open surgery in terms of oncological radicality.
Topics: Disease-Free Survival; Humans; Laparoscopy; Randomized Controlled Trials as Topic; Rectal Neoplasms; Treatment Outcome
PubMed: 34716474
DOI: 10.1007/s00384-021-04048-9 -
Journal of Affective Disorders Jan 2021Personality disorder (PD) may affect the efficacy of pharmacological interventions for mood disorders, but the extent to which this occurs is uncertain. We aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Personality disorder (PD) may affect the efficacy of pharmacological interventions for mood disorders, but the extent to which this occurs is uncertain. We aimed to examine the available published evidence concerning the role of PD in pharmacological treatment outcomes of randomised controlled trials (RCTs) for adults with mood disorders (i.e. depressive and bipolar spectrum disorders).
METHODS
A systematic search of Cochrane Central Register of Controlled Clinical Trials, PubMed, EMBASE, PsycINFO, CINAHL Complete, and Google Scholar databases was undertaken to identify studies of interest. Data were independently extracted by two reviewers. The Cochrane Risk of Bias tool was used to assess methodological quality and risk of bias. A random effects model was utilised and statistical heterogeneity was assessed using the I statistic. This systematic review was registered with PROSPERO (CRD42018089279) and the protocol is published.
RESULTS
The search yielded 11,640 studies. Subsequent to removing duplicates, 9657 studies were screened at title and abstract stage and 1456 were assessed at full-text stage. Eighteen studies met criteria for inclusion in this review. Meta-analysis did not reveal a significant difference between groups for treatment outcome (standardised mean difference 0.22 [-0.09, 0.54]; I: 69%, p=0.17) and remission (risk ratio 0.84 [0.64, 1.11]; I: 51%, p=0.22).
LIMITATIONS
This review was limited by lack of studies on bipolar disorder.
CONCLUSION
PD comorbidity does not appear to affect treatment efficacy of pharmacological interventions for adults with mood disorders.
Topics: Adult; Bipolar Disorder; Humans; Mood Disorders; Personality Disorders; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33197840
DOI: 10.1016/j.jad.2020.10.031 -
GeroScience Dec 2021To date, no meta-analytical study evaluating the benefits of resistance exercise intervention on muscular strength and power and functional capacity in acute... (Meta-Analysis)
Meta-Analysis Review
Resistance exercise intervention on muscular strength and power, and functional capacity in acute hospitalized older adults: a systematic review and meta-analysis of 2498 patients in 7 randomized clinical trials.
To date, no meta-analytical study evaluating the benefits of resistance exercise intervention on muscular strength and power and functional capacity in acute hospitalized older adults was conducted. Then, to synthesize the emerging evidence on the effects of resistance exercise intervention on muscular strength and power and functional capacity in acute hospitalized older adults, two independent authors performed a systematic search (PubMed, Scopus, Web of Science, and SciELO) until January 2021. Randomized clinical trials were included regarding the effects of resistance exercise and hospital usual care. The Cochrane Collaboration assessment tool was used to analyze the risk of bias. The comparisons included muscular strength (isometric handgrip strength and one-repetition maximum test of leg press), muscular power (output during leg press exercise), and functional capacity (timed-up-and-go, and short physical performance battery). Resistance exercise intervention increased muscular strength (isometric handgrip strength: mean difference = 2.50 kg, 95% confidence interval (CI) = 1.33, 3.67; and one-repetition maximum test of leg press: mean difference = 19.28 kg, 95% confidence interval = 14.70, 23.86) and muscular power (mean difference = 29.52 W, 95% confidence interval = 28.84, 30.21), and functional capacity (timed-up-and-go: mean difference = 3.40 s, 95% confidence interval = 0.47, 6.36; and short physical performance battery: mean difference = 1.29 points, 95% confidence interval = 0.10, 2.48) at discharge compared with hospital usual care. This meta-analysis endorses the increase of muscular strength and power gains and improving the functional capacity in favor of resistance exercise intervention in acute hospitalized older adults. TRIAL REGISTRATION : https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020203658.
Topics: Aged; Exercise; Exercise Therapy; Hand Strength; Humans; Muscle Strength; Randomized Controlled Trials as Topic
PubMed: 34453666
DOI: 10.1007/s11357-021-00446-7 -
The Journal of Evidence-based Dental... Dec 2022To compare the clinical and radiographic outcomes of pulpotomies in primary molars using bioactive endodontic materials and ferric sulfate. (Meta-Analysis)
Meta-Analysis Review
COMPARING THE CLINICAL AND RADIOGRAPHIC OUTCOMES OF PULPOTOMIES IN PRIMARY MOLARS USING BIOACTIVE ENDODONTIC MATERIALS AND FERRIC SULFATE - A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS.
OBJECTIVE
To compare the clinical and radiographic outcomes of pulpotomies in primary molars using bioactive endodontic materials and ferric sulfate.
DESIGN
The search was conducted in PubMed, Ebscohost, ProQuest, and Scopus databases till June 2021. Children undergoing pulpotomy therapy in primary molars treated with ferric sulfate (FS) and bioactive endodontic materials were evaluated for clinical and radiographic success. Meta-analysis was performed on a random-effects model to assess the success at 6,12,18, and 24 months. The quality of studies was evaluated using the Cochrane risk of bias tool for randomized trials RESULTS: No significant difference was observed between Mineral trioxide aggregate (MTA) and FS at 24 months for both clinical [RR0.98 (95%CI 0.15,6.34), I = 0%] and radiographic [RR0.74 (95%CI: 0.23,2.43), I = 0%] success. At 6 months [RR1.36 (95%CI: 0.10,19.34), I = 33%], no difference was observed in the clinical [RR1.00 (95%CI: 0.95,1.05), I = 0%] and radiographic success [RR0.99 (95%CI: 0.88,1.11), I = 51%] between Biodentine (BD), FS and radiographic success of calcium enriched cement and FS [RR0.25 (95%CI: 0.03, 2.22), I = 0%].
CONCLUSION
Amongst bioactive materials, MTA and FS demonstrated equal success rates in both clinical and radiographic outcomes with follow-up periods of up to 24 months. Future, high-quality trials are required to verify the result of the current review.
Topics: Child; Humans; Tooth, Deciduous; Molar; Randomized Controlled Trials as Topic; Pulpotomy; Treatment Outcome
PubMed: 36494111
DOI: 10.1016/j.jebdp.2022.101770 -
Graefe's Archive For Clinical and... Aug 2023To perform a qualitative analysis of outcomes published from randomized controlled trials (RCTs) on central serous chorioretinopathy (CSCR) from 1979 to 2022. (Review)
Review
PURPOSE
To perform a qualitative analysis of outcomes published from randomized controlled trials (RCTs) on central serous chorioretinopathy (CSCR) from 1979 to 2022.
DESIGN
Systematic review.
METHODS
All RCTs (including both therapeutic and non-therapeutic interventions) on CSCR available online till July 2022 were included after an electronic search in multiple databases such as PubMed, CENTRAL, MEDLINE, EMBASE, BIOSIS, Scopus, and Cochrane database. We analyzed and compared the inclusion criteria, imaging modalities, study endpoints, duration, and the results of the study.
RESULTS
The literature search yielded 498 potential publications. After excluding duplicate studies and studies that met clear exclusion criteria, 64 were screened for further evaluation, of which 7 were removed due to a lack of necessary inclusion criteria. A total of 57 eligible studies are described in this review.
CONCLUSION
This review provides a comparative overview of key outcomes reported between RCTs investigating CSCR. We describe the current landscape of treatment modalities for CSCR and note the discrepancies between results in these published studies. Challenges arise when attempting to compare similar study designs without comparable outcome measures (i.e., clinical vs. structural) which may limit the overall evidence presented. To mitigate this issue, we present the collected data from each study in tables detailing the measures that are and are not assessed in each publication.
Topics: Humans; Central Serous Chorioretinopathy; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36862202
DOI: 10.1007/s00417-023-05996-4 -
Journal of the National Cancer Institute Apr 2020The US Food and Drug Administration's accelerated approval and later withdrawal of bevacizumab in patients with metastatic breast cancer (mBC) is a seminal case for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The US Food and Drug Administration's accelerated approval and later withdrawal of bevacizumab in patients with metastatic breast cancer (mBC) is a seminal case for ongoing debates about the validity of using progression-free survival (PFS) as a surrogate measure for overall survival (OS) in cancer drug approvals. We systematically reviewed and meta-analyzed the evidence around bevacizumab's regulatory approval and withdrawal in mBC.
METHODS
We searched for all published phase II or III clinical trials testing bevacizumab as a first-line therapy for patients with mBC. Data were extracted on trial demographics, interventions, and outcomes. Descriptive analysis was stratified by whether the trial was initiated before, during, or after the accelerated approval. We used a cumulative random-effects meta-analysis to assess the evolution of evidence of the effect of bevacizumab on PFS and OS. We estimated the association between the trial-level PFS and OS effect using a nonlinear mixed-regression model.
RESULTS
Fifty-two studies were included. Trial activity dramatically dropped after the accelerated approval was withdrawn. Eight clinical trials reported hazard ratios (hazard ratios) and were meta-analyzed. The cumulative hazard ratio for PFS was 0.72 (95% CI = 0.65 to 0.79), and the cumulative hazard ratio for OS was 0.90 (95% CI = 0.80 to 1.01). The regression model showed a statistically nonsignificant association between PFS benefit and OS benefit (β = 0.43, SE = 0.81).
CONCLUSION
The US Food and Drug Administration's decision-making in this case was consistent with the evolving state of evidence. However, the fact that seven clinical trials are insufficient to conclude validity (or lack thereof) for a trial-level surrogate suggests that it would be more efficient to conduct trials using the more clinically meaningful endpoints.
Topics: Antineoplastic Agents, Immunological; Bevacizumab; Breast Neoplasms; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Decision Making; Drug Approval; Endpoint Determination; Female; Humans; Legislation, Drug; Neoplasm Metastasis; Nonlinear Dynamics; Progression-Free Survival; Randomized Controlled Trials as Topic; Regression Analysis; Survival Rate; United States; United States Food and Drug Administration
PubMed: 31651981
DOI: 10.1093/jnci/djz211 -
Toxins Apr 2024Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of... (Review)
Review
Botulinum toxin type A (BONT-A) has shown promise in improving the mood-related symptoms of psychiatric disorders by targeting muscles linked to the expression of negative emotions. We conducted a systematic review of past and ongoing efficacy trials of BONT-A therapy for psychiatric disorders to identify relevant trends in the field and discuss the refinement of therapeutic techniques. A comprehensive search for published clinical trials using BONT-A injections for psychiatric disorders was performed on 4 May 2023 through OVID databases (MEDLINE, Embase, APA PsycINFO). Unpublished clinical trials were searched through the ClinicalTrials.gov and International Clinical Trial Registry Platform public registries. The risk of bias was assessed using the JBI Critical Appraisal tools for use in systematic reviews. We identified 21 studies (17 published, 4 unpublished clinical trials) involving 471 patients. The studies focused on evaluating the efficacy of BONT-A for major depressive, borderline personality, social anxiety, and bipolar disorders. BONT-A was most commonly injected into the glabellar area, with an average dose ranging between 37.75 U and 44.5 U in published studies and between 32.7 U and 41.3 U in unpublished trials. The results indicated significant symptom reductions across all the studied psychiatric conditions, with mild adverse effects. Thus, BONT-A appears to be safe and well-tolerated for psychiatric disorders of negative affectivity. However, despite the clinical focus, there was a noted shortage of biomarker-related assessments. Future studies should focus on pursuing mechanistic explorations of BONT-A effects at the neurobiological level.
Topics: Humans; Mental Disorders; Botulinum Toxins, Type A; Clinical Trials as Topic; Treatment Outcome
PubMed: 38668616
DOI: 10.3390/toxins16040191 -
Journal of Intensive Care Medicine Feb 2020Conflicting data exists on the pharmacologic management of intensive care unit (ICU) delirium. This review appraises the current evidence of pharmacologic management of...
PURPOSE
Conflicting data exists on the pharmacologic management of intensive care unit (ICU) delirium. This review appraises the current evidence of pharmacologic management of ICU delirium.
MATERIALS AND METHODS
A systematic literature search of MEDLINE and Embase was conducted to answer the population, intervention, comparison, and outcome (PICO) question of: "Does the use of a pharmacologic agent compared to standard of care or placebo improve ICU delirium in a critically ill patient population?"
RESULTS
After application of the PICO question and the inclusion and exclusion criteria, 13 articles were included. Of these articles, 7 were prospective randomized controlled trials, 1 was a prospective nonrandomized controlled trial, and 5 were retrospective investigations. The included articles differed in the agents evaluated, primary outcome, and method of identifying delirium.
CONCLUSION
The variability of outcomes illustrates the need for a large-scale investigation to further evaluate the role of pharmacologic management of ICU delirium.
Topics: Antipsychotic Agents; Clinical Trials as Topic; Critical Care; Critical Care Outcomes; Delirium; Humans; Intensive Care Units; Prospective Studies; Retrospective Studies; Standard of Care; Treatment Outcome
PubMed: 30309280
DOI: 10.1177/0885066618805965 -
CNS Drugs Oct 2019Roughly 80% of the symptom improvement experienced on antidepressants in clinical trials is also observed in the placebo comparison group. Understanding the correlates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Roughly 80% of the symptom improvement experienced on antidepressants in clinical trials is also observed in the placebo comparison group. Understanding the correlates of placebo improvement and response is important to designing efficient and successful trials of future antidepressants.
OBJECTIVE
The objective of this meta-analysis was to investigate the magnitude of placebo symptom improvement and placebo response rates in second-generation antidepressant trials of depression, anxiety, and obsessive-compulsive disorder.
METHODS
We searched PubMed on 10 June, 2016, with no date or language limits, to identify randomized placebo-controlled trials of second-generation antidepressants in adults with depression, anxiety, or obsessive-compulsive disorder. We used a random-effects meta-analysis to examine the magnitude of placebo symptom improvement using standardized mean difference and placebo response rate. Stratified subgroup analysis and meta-regression were utilized to examine the effect of diagnostic indication and correlates of placebo symptom improvement.
RESULTS
The meta-analysis included 164 trials involving 19,591 participants. Magnitude of placebo improvement and placebo response rates varied significantly between diagnostic indications. The magnitude of placebo improvement was much lower in obsessive-compulsive disorder (standardized mean difference = 0.58, 95% confidence interval 0.36-0.79) than in depression (standardized mean difference = 1.22, 95% confidence interval 1.12-1.32) or anxiety (standardized mean difference = 1.01, 95% confidence interval 0.90-1.12) trials. There was a large amount of heterogeneity in placebo improvement between studies (Q = 899, df = 110, p < 0.001, I = 88%). A greater number of study sites and a later publication year were associated with a greater magnitude of placebo improvement and response rate. Presence of a placebo lead-in and absence of non-US sites were associated with a reduced magnitude of placebo improvement. Trial duration was positively associated with the magnitude of placebo improvement in depression trials but negatively associated with the magnitude of placebo improvement in anxiety and obsessive-compulsive disorder trials.
CONCLUSIONS
Magnitude of placebo symptom improvement differed significantly based on diagnostic indication with improvement being significantly less in obsessive-compulsive disorder than anxiety and depression. Some trial characteristics were associated with a greater magnitude of placebo improvement in trials across disorders but others were disorder specific.
Topics: Antidepressive Agents, Second-Generation; Anxiety; Clinical Trials as Topic; Depression; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic
PubMed: 31573058
DOI: 10.1007/s40263-019-00662-y -
JAMA Jun 2024Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening.
OBJECTIVE
To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening.
DESIGN, SETTING, AND PARTICIPANTS
This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer.
EXPOSURES
Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening.
MAIN OUTCOMES AND MEASURES
End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis.
RESULTS
The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, -0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, -0.27 to 0.80]) and prostate (Pearson ρ = -0.69 [95% CI, -0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and -3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004).
CONCLUSIONS AND RELEVANCE
In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.
Topics: Female; Humans; Male; Early Detection of Cancer; Endpoint Determination; Incidence; Neoplasm Staging; Neoplasms; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 38583868
DOI: 10.1001/jama.2024.5814