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Journal of Cachexia, Sarcopenia and... Jun 2024Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary... (Review)
Review
Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.
Topics: Humans; Cachexia; Neoplasms; Body Composition; Body Weight; Clinical Trials as Topic
PubMed: 38738581
DOI: 10.1002/jcsm.13478 -
Current Problems in Cardiology Jul 2024The ideal surgical intervention for secondary mitral regurgitation (SMR), a disease of the left ventricle not the mitral valve itself, is still debated. We performed an... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Long-term outcomes comparison of mitral valve repair or replacement for secondary mitral valve regurgitation. An updated systematic review and reconstructed time-to-event study-level meta-analysis.
BACKGROUND AND AIM
The ideal surgical intervention for secondary mitral regurgitation (SMR), a disease of the left ventricle not the mitral valve itself, is still debated. We performed an updated systematic review and study-level meta-analysis investigating mitral valve repair (MVr) versus mitral valve replacement (MVR) for adult patients with SMR, with or without coronary artery disease (CAD).
METHODS
PubMed, CENTRAL and EMBASE were searched for studies comparing MVr versus MVR. Randomized trial or observational studies were considered eligible. Primary endpoint was long-term mortality for any cause. Kaplan-Meier survival curves were reconstructed and compared with Cox linear regression. Landmark analysis and time-varying hazard ratio (HR) were analyzed. Sensitivity analyses included meta-regression and separate sub-analysis. A random effects model was used.
RESULTS
Twenty-three studies (MVr=3,727 and MVR=2,839) were included. One study was a randomized trial, and 19 studies were adjusted. The mean weighted follow-up was 3.7±2.8 years. MVR was associated with significative greater late mortality (HR=1.26; 95 % CI, 1.14-1.39; P<0.0001) at 10-year follow-up. There was a time-varying trend showing an increased risk of mortality in the first 2 years after MVR (HR=1.38; 95 % CI, 1.21-1.56; P<0.0001), after which this difference dissipated (HR=0.94; 95 % CI, 0.81-1.09; P=0.41). Separate sub-analyses showed comparable long-term mortality in patients with concomitant coronary surgery ≥90 %, left ventricle ejection fraction ≤40 %, and sub-valvular apparatus preservation rate of 100 %.
CONCLUSIONS
Compared to repair, MVR is associated with higher probability of mortality in the first 2 years following surgery, after which the two procedures showed comparable late mortality rate.
Topics: Humans; Mitral Valve Insufficiency; Heart Valve Prosthesis Implantation; Mitral Valve; Treatment Outcome; Mitral Valve Annuloplasty; Time Factors
PubMed: 38735348
DOI: 10.1016/j.cpcardiol.2024.102636 -
Critical Care (London, England) May 2024An increasing number of patients requires extracorporeal membrane oxygenation (ECMO) for life support. This supportive modality is associated with nosocomial infections... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An increasing number of patients requires extracorporeal membrane oxygenation (ECMO) for life support. This supportive modality is associated with nosocomial infections (NIs). This systematic review and meta-analysis aim to assess the incidence and risk factors of NIs in adult.
METHODS
We searched PubMed, Scopus, Web of Science, and ProQuest databases up to 2022. The primary endpoint was incidence of NI. Secondary endpoints included time to infection, source of infection, ECMO duration, Intensive care and hospital length of stay (LOS), ECMO survival and overall survival. Incidence of NI was reported as pooled proportions and 95% confidence intervals (CIs), while dichotomous outcomes were presented as risk ratios (RR) as the effective index and 95% CIs using a random-effects model.
RESULTS
Among the 4,733 adult patients who received ECMO support in the 30 included studies, 1,249 ECMO-related NIs per 1000 ECMO-days was observed. The pooled incidence of NIs across 18 studies involving 3424 patients was 26% (95% CI 14-38%).Ventilator-associated pneumonia (VAP) and bloodstream infections (BSI) were the most common NI sources. Infected patients had lower ECMO survival and overall survival rates compared to non-infected patients, with risk ratio values of 0.84 (95% CI 0.74-0.96, P = 0.01) and 0.80 (95% CI 0.71-0.90, P < 0.001), respectively.
CONCLUSION
Results showed that 16% and 20% lower of ECMO survival and overall survival in patients with NI than patients without NI, respectively. However, NI increased the risk of in-hospital mortality by 37% in infected patients compared with non-infected patients. In addition, this study identified the significant positive correlation between ECMO duration and ECMO-related NI.
Topics: Humans; Extracorporeal Membrane Oxygenation; Cross Infection; Incidence; Risk Factors; Adult
PubMed: 38730424
DOI: 10.1186/s13054-024-04946-8 -
Cancer Research and Treatment May 2024Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology,...
PURPOSE
Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety.
MATERIALS AND METHODS
We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles.
RESULTS
Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported.
CONCLUSION
Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.
PubMed: 38726510
DOI: 10.4143/crt.2024.128 -
The Cochrane Database of Systematic... May 2024Collaborative care for severe mental illness (SMI) is a community-based intervention that promotes interdisciplinary working across primary and secondary care.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Collaborative care for severe mental illness (SMI) is a community-based intervention that promotes interdisciplinary working across primary and secondary care. Collaborative care interventions aim to improve the physical and/or mental health care of individuals with SMI. This is an update of a 2013 Cochrane review, based on new searches of the literature, which includes an additional seven studies.
OBJECTIVES
To assess the effectiveness of collaborative care approaches in comparison with standard care (or other non-collaborative care interventions) for people with diagnoses of SMI who are living in the community.
SEARCH METHODS
We searched the Cochrane Schizophrenia Study-Based Register of Trials (10 February 2021). We searched the Cochrane Common Mental Disorders (CCMD) controlled trials register (all available years to 6 June 2016). Subsequent searches on Ovid MEDLINE, Embase and PsycINFO together with the Cochrane Central Register of Controlled Trials (with an overlap) were run on 17 December 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) where interventions described as 'collaborative care' were compared with 'standard care' for adults (18+ years) living in the community with a diagnosis of SMI. SMI was defined as schizophrenia, other types of schizophrenia-like psychosis or bipolar affective disorder. The primary outcomes of interest were: quality of life, mental state and psychiatric admissions at 12 months follow-up.
DATA COLLECTION AND ANALYSIS
Pairs of authors independently extracted data. We assessed the quality and certainty of the evidence using RoB 2 (for the primary outcomes) and GRADE. We compared treatment effects between collaborative care and standard care. We divided outcomes into short-term (up to six months), medium-term (seven to 12 months) and long-term (over 12 months). For dichotomous data we calculated the risk ratio (RR) and for continuous data we calculated the standardised mean difference (SMD), with 95% confidence intervals (CIs). We used random-effects meta-analyses due to substantial levels of heterogeneity across trials. We created a summary of findings table using GRADEpro.
MAIN RESULTS
Eight RCTs (1165 participants) are included in this review. Two met the criteria for type A collaborative care (intervention comprised of the four core components). The remaining six met the criteria for type B (described as collaborative care by the trialists, but not comprised of the four core components). The composition and purpose of the interventions varied across studies. For most outcomes there was low- or very low-certainty evidence. We found three studies that assessed the quality of life of participants at 12 months. Quality of life was measured using the SF-12 and the WHOQOL-BREF and the mean endpoint mental health component scores were reported at 12 months. Very low-certainty evidence did not show a difference in quality of life (mental health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.03, 95% CI -0.26 to 0.32; 3 RCTs, 227 participants). Very low-certainty evidence did not show a difference in quality of life (physical health domain) between collaborative care and standard care in the medium term (at 12 months) (SMD 0.08, 95% CI -0.18 to 0.33; 3 RCTs, 237 participants). Furthermore, in the medium term (at 12 months) low-certainty evidence did not show a difference between collaborative care and standard care in mental state (binary) (RR 0.99, 95% CI 0.77 to 1.28; 1 RCT, 253 participants) or in the risk of being admitted to a psychiatric hospital at 12 months (RR 5.15, 95% CI 0.67 to 39.57; 1 RCT, 253 participants). One study indicated an improvement in disability (proxy for social functioning) at 12 months in the collaborative care arm compared to usual care (RR 1.38, 95% CI 0.97 to 1.95; 1 RCT, 253 participants); we deemed this low-certainty evidence. Personal recovery and satisfaction/experience of care outcomes were not reported in any of the included studies. The data from one study indicated that the collaborative care treatment was more expensive than standard care (mean difference (MD) international dollars (Int$) 493.00, 95% CI 345.41 to 640.59) in the short term. Another study found the collaborative care intervention to be slightly less expensive at three years.
AUTHORS' CONCLUSIONS
This review does not provide evidence to indicate that collaborative care is more effective than standard care in the medium term (at 12 months) in relation to our primary outcomes (quality of life, mental state and psychiatric admissions). The evidence would be improved by better reporting, higher-quality RCTs and the assessment of underlying mechanisms of collaborative care. We advise caution in utilising the information in this review to assess the effectiveness of collaborative care.
Topics: Adult; Humans; Bias; Bipolar Disorder; Community Mental Health Services; Mental Disorders; Patient Care Team; Quality of Life; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 38712709
DOI: 10.1002/14651858.CD009531.pub3 -
Clinical and Translational Science May 2024No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and... (Review)
Review
No systematic review of trial designs in patients with relapsing multiple sclerosis (RMS) was reported. This systematic review was conducted on the trial designs and primary end points (PEs) of phase II and III trials intended to modify the natural course of the disease in patients with RMS. The purpose of the study is to explore trends/topics and discussion points in clinical trial design and PE, comparing them to regulatory guidelines and expert recommendations. Three trial registration systems, ClinicalTrials.gov, the EU Clinical Trials Register, and the Japan Registry of Clinical Trials, were used and 60 trials were evaluated. The dominant clinical trial design was a randomized controlled parallel-arms trial and other details were as follows: in adult phase III confirmatory trials (n = 32), active-controlled double-blind trial (DBT) (53%) and active-controlled open-label assessor-masking trial (16%); in adult phase II dose-finding trials (n = 9), placebo- and active-controlled DBT (44%), placebo-controlled DBT (22%), and placebo-controlled add-on DBT (22%); and in pediatric phase III confirmatory trials (n = 8), active-controlled DBT (38%) and active-controlled open-label non-masking trial (25%). The most common PEs were as follows: in adult confirmatory trials, annual relapse rate (ARR) (56%) and no evidence of disease activity-3 (NEDA-3) (13%); in adult dose-finding trials, the cumulative number of T1 gadolinium-enhancing lesions (56%), combined unique active lesions (22%), and overall disability response score (22%); and in pediatric confirmatory trials, ARR (38%) and time to first relapse (25%). It was suggested that some parts of the regulatory guidelines and expert recommendations need to be revised.
Topics: Humans; Clinical Trials, Phase III as Topic; Clinical Trials, Phase II as Topic; Adult; Multiple Sclerosis, Relapsing-Remitting; Child; Research Design; Endpoint Determination; Randomized Controlled Trials as Topic
PubMed: 38708586
DOI: 10.1111/cts.13794 -
Annals of Medicine and Surgery (2012) May 2024Recent guidelines suggest that antiplatelet therapy (APT) is the standard of care in the absence of long-term oral anticoagulation (OAC) indications in patients... (Review)
Review
Efficacy and outcomes of antiplatelet therapy versus oral anticoagulants in patients undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis.
BACKGROUND
Recent guidelines suggest that antiplatelet therapy (APT) is the standard of care in the absence of long-term oral anticoagulation (OAC) indications in patients post-transcatheter aortic valve replacement (TAVR). The superiority of one method over the other remains controversial.
MATERIALS AND METHODS
Several databases, including MEDLINE, Google Scholar, and EMBASE, were electronically searched. The primary endpoint was the all-cause mortality (ACM) rate. Secondary endpoints included cardiovascular death, myocardial infarction (MI), stroke/TIA, haemorrhagic stroke, bleeding events, systemic embolism, and valve thrombosis in post-TAVR patients receiving APT and oral anticoagulants (OACs). Forest plots were generated using Review Manager version 5.4, with a value less than 0.05 indicating statistical significance. Subgroup analysis was performed to explore potential sources of heterogeneity.
RESULTS
Twelve studies were selected. No significant differences were observed in APT and OAC group for ACM [risk ratio (RR): 0.67; 95% CI:0.45-1.01; =0.05], cardiovascular death [RR:0.91; 95% CI:0.73-1.14; =0.42], MI [RR:1.69; 95% CI:0.43-6.72; =0.46], Stroke/TIA [RR:0.79; 95% CI:0.58-1.06; =0.12], ischaemic stroke [RR:0.83; 95% CI:0.50-1.37; =0.47], haemorrhagic stroke [RR:1.08; 95% CI: 0.23-5.15; =0.92], major bleeding [RR:0.79; 95% CI:0.51-1.21; =0.28], minor bleeding [RR:1.09; 95% CI: 0.80-1.47; =0.58], life-threatening bleeding [RR:0.85; 95% CI:0.55-1.30; =0.45], any bleeding [RR:0.98; 95% CI:0.83-1.15; =0.78], and systemic embolism [RR:0.87; 95% CI:0.44-1.70; =0.68]. The risk of valve thrombosis was higher in patients receiving APT than in those receiving OAC [RR:2.61; 95% CI:1.56-4.36; =0.0002].
CONCLUSIONS
Although the risk of valve thrombosis increased in patients receiving APT, the risk of other endpoints was comparable between the two groups.
PubMed: 38694361
DOI: 10.1097/MS9.0000000000001908 -
Avicenna Journal of Medicine Jan 2024Conflicting evidence regarding the laparoscopic versus open cholecystectomy outcomes in scientific literature impacts the medical decision-making for patients with... (Review)
Review
Conflicting evidence regarding the laparoscopic versus open cholecystectomy outcomes in scientific literature impacts the medical decision-making for patients with gallbladder disease. This study aimed to compare a range of primary and secondary outcomes between patients receiving laparoscopic cholecystectomy and those with open intervention. Articles published from 1993 to 2023 were explored by utilizing advanced filters of PubMed Central/Medline, Web of Science, CINAHL, JSTOR, Cochrane Library, Scopus, and EBSCO. The gallbladder disease was determined by the presence of one or more of the following conditions: 1) Gangrenous cholecystitis, 2) acute cholecystitis, 3) chronic gallbladder diseases, and 4) cholelithiasis. The primary end-point was mortality, while the secondary outcome included (1) bile leakage, 2) common bile duct injury, 3) gangrene, 4) hospital stay (days), 5) major complications, 6) median hospital stay (days), (7) pneumonia, 8) sick leaves (days), and 9) wound infection. Statistically significant reductions were observed in mortality (odds ratio [OR]: 0.30, 95% confidence interval [CI]: 0.30, 0.45, < 0.00001), mean hospital stay duration (mean difference: -2.68, 95% CI: -3.66, -1.70, < 0.00001), major complications (OR: 0.35, 95% CI: 0.19, 0.64, = 0.0005), post/intraoperative wound infection (OR: 0.29, 95% CI: 0.16, 0.51, < 0.0001), and sick leaves (OR: 0.34, 95% CI: 0.14, 0.80, = 0.01) in patients who underwent laparoscopic cholecystectomy compared with those with the open intervention. No statistically significant differences were recorded between the study groups for bile leakage, common bile duct injury, gangrene, median hospital stay days, and pneumonia ( > 0.05). The pooled outcomes favored the use of laparoscopic cholecystectomy over the open procedure in patients with gallbladder disease. The consolidated findings indicate the higher impact of laparoscopic cholecystectomy in improving patient outcomes, including safety episodes, compared with open cholecystectomy.
PubMed: 38694141
DOI: 10.1055/s-0043-1777710 -
Asian Journal of Urology Apr 2024To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space. (Review)
Review
OBJECTIVE
To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space.
METHODS
We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results.
RESULTS
In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% . 46% to 100% . 61%. CRP was a predictor of better CSS (hazard ratio 0.264, =0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% 90.8%, <0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%.
CONCLUSION
CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease.
PubMed: 38680575
DOI: 10.1016/j.ajur.2022.03.017 -
Alzheimer's Research & Therapy Apr 2024Clinical trials in Alzheimer's disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a...
BACKGROUND
Clinical trials in Alzheimer's disease (AD) had high failure rates for several reasons, including the lack of biological endpoints. Fluid-based biomarkers may present a solution to measure biologically relevant endpoints. It is currently unclear to what extent fluid-based biomarkers are applied to support drug development.
METHODS
We systematically reviewed 272 trials (clinicaltrials.gov) with disease-modifying therapies starting between 01-01-2017 and 01-01-2024 and identified which CSF and/or blood-based biomarker endpoints were used per purpose and trial type.
RESULTS
We found that 44% (N = 121) of the trials employed fluid-based biomarker endpoints among which the CSF ATN biomarkers (Aβ (42/40), p/tTau) were used most frequently. In blood, inflammatory cytokines, NFL, and pTau were most frequently employed. Blood- and CSF-based biomarkers were used approximately equally. Target engagement biomarkers were used in 26% (N = 72) of the trials, mainly in drugs targeting inflammation and amyloid. Lack of target engagement markers is most prominent in synaptic plasticity/neuroprotection, neurotransmitter receptor, vasculature, epigenetic regulators, proteostasis and, gut-brain axis targeting drugs. Positive biomarker results did not always translate to cognitive effects, most commonly the small significant reductions in CSF tau isoforms that were seen following anti-Tau treatments. On the other hand, the positive anti-amyloid trials results on cognitive function were supported by clear effect in most fluid markers.
CONCLUSIONS
As the field moves towards primary prevention, we expect an increase in the use of fluid-based biomarkers to determine disease modification. Use of blood-based biomarkers will rapidly increase, but CSF markers remain important to determine brain-specific treatment effects. With improving techniques, new biomarkers can be found to diversify the possibilities in measuring treatment effects and target engagement. It remains important to interpret biomarker results in the context of the trial and be aware of the performance of the biomarker. Diversifying biomarkers could aid in the development of surrogacy biomarkers for different drug targets.
Topics: Alzheimer Disease; Humans; Biomarkers; Clinical Trials as Topic; tau Proteins; Amyloid beta-Peptides
PubMed: 38678292
DOI: 10.1186/s13195-024-01456-1