Results Of Randomized Controlled Trials Research Articles

Efficacy of non-pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases

ObjectiveTo identify the best evidence on the efficacy of non-pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the...

Endovascular revascularization vs. open surgical revascularization for patients with lower extremity artery disease: a systematic review and meta-analysis.

Currently, the main treatment for lower extremity artery disease (LEAD) is revascularization, including endovascular revascularization (EVR) and open surgical revascularization (OSR), but the specific revascularization strategy for LEAD is controversial. This review provided the comprehensive and recent evidence for the treatment of LEAD. Medline, Embase, and the Cochrane Library databases were searched for relevant articles. Randomized controlled trials (RCTs) and cohort studies comparing the short-term or long-term outcomes between EVR and OSR of LEAD were identified. Short-term outcomes were 30-day mortality, major amputation, wound complication, major adverse cardiovascular events (MACEs), and length of hospital stay (LOS), while long-term outcomes included overall survival (OS), amputation-free survival (AFS), freedom from re-intervention (FFR), primary patency (PP), and secondary patency (SP). 11 RCTs and 105 cohorts involving 750,134 patients were included in this analysis. For the pooled results of cohort studies, EVR markedly decreased the risk of 30-day mortality, wound complication, MACEs, LOS, but increased the risk of OS, FFR, PP, and SP. For the pooled outcomes of RCTs, EVR was associated with obviously lower 30-day mortality, less wound complication and shorter LOS, but higher risk of PP, and SP. However, both RCTs and cohorts did not show obvious difference in 30-day major amputation and AFS. Both the pooled results of cohorts and RCTs indicated that EVR was associated with a lower short-term risk for LEAD, while OSR was accompanied by a substantially lower long-term risk. Therefore, the life expectancy of LEAD should be strictly considered when choosing the revascularization modality. As the current findings mainly based on data of retrospective cohort studies, additional high-quality studies are essential to substantiate these results. https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022317239.

Patient-Reported Outcome Measures in Liver and Gastrointestinal Cancer Randomized Controlled Trials.

For many years, outcomes such as mortality and morbidity were the standard for evaluating oncological treatment effectiveness. With the introduction of patient-reported outcome measures (PROMs), the focus shifted from a mere extension of a patient's life or release from disease to the improvement of a multilayered concept of health, decisively affecting life satisfaction. In this study, we deal with the topic of PROMs in liver and gastrointestinal randomized controlled trials. The final database included 43 papers reporting results of randomized controlled trials (RCTs) for liver or gastrointestinal cancer interventions where one of the primary or secondary outcomes was a health-related quality of life measure. The most often used PROM was the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for both liver cancer and gastrointestinal cancer (in 62% of gastrointestinal cancer studies and 57% of liver cancer studies). For the gastrointestinal cancer group, the QLQ-STO22, a cancer-specific extension of the QLQ-C30, was the second most commonly used PROM. In liver cancer, the generic PROM Short Form 36 and the EORTC QLQ-HCC18, a cancer-specific extension of the QLQ-C30, were the second most commonly used PROMs. We found that RCTs often do not include comprehensive quality-of-life measures. When quality of life is part of an RCT, it is often only a secondary outcome. For a holistic view of the patient, a stronger integration and weighting of patient-reported outcomes in RCTs would be desirable.

Analysis of phase III clinical trials in metastatic NSCLC to assess the correlation between QoL results and survival outcomes

BackgroundIn addition to improving survival outcomes, new oncology treatments should lead to amelioration of patients’ quality of life (QoL). Herein, we examined whether QoL results correlated with PFS and OS outcomes in phase III randomized controlled trials (RCTs) investigating new systemic treatments in metastatic non-small cell lung cancer (NSCLC).MethodsThe systematic search of PubMed was conducted in October 2022. We identified 81 RCTs testing novel drugs in metastatic NSCLC and published in the English language in a PubMed-indexed journal between 2012 and 2021. Only trials reporting QoL results and at least one survival outcome between OS and PFS were selected. For each RCT, we assessed whether global QoL was “superior,” “inferior,” or with “non-statistically significant difference” in the experimental arm compared to the control arm.ResultsExperimental treatments led to superior QoL in 30 (37.0%) RCTs and inferior QoL in 3 (3.7%) RCTs. In the remaining 48 (59.3%) RCTs, a statistically significant difference between the experimental and control arms was not found. Of note, we found a statistically significant association between QoL and PFS improvements (X2 = 3.93, p = 0.0473). In more detail, this association was not significant in trials testing immunotherapy or chemotherapy. On the contrary, in RCTs testing target therapies, QoL results positively correlated with PFS outcomes (p = 0.0196). This association was even stronger in the 32 trials testing EGFR or ALK inhibitors (p = 0.0077). On the other hand, QoL results did not positively correlate with OS outcomes (X2 = 0.81, p = 0.368). Furthermore, we found that experimental treatments led to superior QoL in 27/57 (47.4%) trials with positive results and in 3/24 (12.5%) RCTs with negative results (p = 0.0028). Finally, we analyzed how QoL data were described in publications of RCTs in which QoL outcomes were not improved (n = 51). We found that a favorable description of QoL results was associated with sponsorship by industries (p = 0.0232).ConclusionsOur study reveals a positive association of QoL results with PFS outcomes in RCTs testing novel treatments in metastatic NSCLC. This association is particularly evident for target therapies. These findings further emphasize the relevance of an accurate assessment of QoL in RCTs in NSCLC.

Statistical Fragility of Randomized Controlled Trials Evaluating Rehabilitation After Arthroscopic Rotator Cuff Repair.

Clinical decision-making often relies on evidence-based medicine, derived from objective data with conventional and rigorous statistical tests to evaluate significance. The literature surrounding rehabilitation after rotator cuff repair (RCR) is conflicting, with no defined standard of practice. To determine the fragility index (FI) and the fragility quotient (FQ) of randomized controlled trials (RCTs) evaluating rehabilitation protocols after RCR. Systematic review. A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by searching the PubMed, Cochrane Library, and Embase databases for RCTs evaluating rehabilitation protocols after arthroscopic RCRs from 2000 to June 1, 2022. The FI was determined by manipulating the dichotomous outcome events from each article until a reversal of significance with 2 × 2 contingency tables was achieved. The FQ was determined by dividing the FI by the sample size. Fourteen RCTs with 48 dichotomous outcomes were ultimately included for analysis. The mean FI for the included dichotomous outcomes was 4 (interquartile range, 3-6), suggesting that the reversal of 4 events is required to change study significance. The mean FQ was 0.048. Of the RCTs that reported data regarding loss to follow-up, most studies (58.5%) indicated that >4 patients had been lost to follow-up. The results of RCT studies of RCR rehabilitation protocols are moderately fragile, something clinicians should be aware of when implementing study results into practice. We recommend the inclusion of FI and FQ in addition to standard P values when reporting statistical results in future RCTs with dichotomous outcome variables on this topic.

Re-conceptualizing SMART designs as a hybrid of randomized and regression discontinuity designs: opportunities, cautions

ABSTRACT Though previously unacknowledged, a SMART (Sequential Multiple Assignment Randomized Trial) design uses both regression discontinuity (RD) and randomized controlled trial (RCT) designs. This combination structure creates a conceptual symbiosis between the two designs that enables both RCT- and previously unrecognized, RD-based inferential claims. In Phase 1, based on a quantitative cut-point, a SMART design yields successful or unsuccessful participants after the initial RCT. In Phase 2, interventions are randomly assigned to successful and unsuccessful, Phase 1 subgroups, thereby yielding both RCT and RD results. Like RCT-based inferences, many but not all newly recognized, RD-based SMART inferences are potentially unbiased. In particular, comparisons between RCT and RD outcomes are potentially problematic. Principles from the within-study comparison literature are used to inform SMART-based research, thereby introducing otherwise ignored inferential and procedural possibilities. Awareness of RD designs embedded within SMARTs encourages previously unrecognized inferential claims, though potential internal validity threats and limitations must be carefully weighed. Finally, new, SMART-like sequences of quasi-experiments and experiments can be tested and embedded logic applied.

Mechanical Thrombectomy for Large Ischemic Stroke: A Systematic Review and Meta-analysis.

There is growing evidence for endovascular thrombectomy (EVT) in patients with large ischemic core infarct and large vessel occlusion (LVO). The objective of this study was to compare the efficacy and safety of EVT vs medical management (MM) using a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs). We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to mechanical thrombectomy for large ischemic core from inception until February 10, 2023. The primary outcome was independent ambulation (modified Rankin Scale [mRS] 0-3). Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. The quality of articles was evaluated through the Cochrane risk assessment tool and the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42023396232). A total of 5,395 articles were obtained through the search and articles that did not meet the inclusion criteria were excluded by review of the title, abstract, and full text. Finally, 3 RCTs and 10 cohort studies met the inclusion criteria. The RCT analysis showed that EVT improved the 90-day functional outcomes of patients with large ischemic core with high-quality evidence, including independent ambulation (mRS 0-3: RR 1.78, 95% CI 1.28-2.48, p < 0.001) and functional independence (mRS 0-2: RR 2.59, 95% CI 1.89-3.57, p < 0.001), but without significantly increasing the risk of symptomatic intracranial hemorrhage (sICH: RR 1.83, 95% CI 0.95-3.55, p = 0.07) or early mortality (RR 0.95, 95% CI 0.78-1.16, p = 0.61). Analysis of the cohort studies showed that EVT improved functional outcomes of patients without an increase in the incidence in sICH. This systematic review and meta-analysis indicates that in patients with LVO stroke with a large ischemic core, EVT was associated with improved functional outcomes over MM without increasing sICH risk. The results of ongoing RCTs may provide further insight in this patient population.

Imbalance in treatment discontinuation without progression between experimental and control arms among randomized trials in advanced breast cancer.

1110 Background: In Randomized Controlled Trials (RCT), treatment discontinuation (TD) can result in censoring. Imbalanced frequency of TD between arms could impact interpretation of results. Here, we quantify TD between the experimental and control arms among RCT supporting registration of drugs for advanced breast cancer. Methods: We identified RCT supporting US Food and Drug Administration's approval of drugs for advanced breast cancer between 2013 and 2023. We extracted data for the number of participants with TD for reasons other than disease progression (PD), death, or completion of treatment. Odds ratio (OR) for TD comparing experimental to control arms were determined for each trial. To assess progression-free survival (PFS) translation into an overall survival (OS) benefit, we calculated hazard ratio (HR) for PFS/OS. Then we assessed whether there was quantitative association between the OR for TD and the ratio of HR for PFS/OS. Quantitative significance was defined according to the criteria of Burnand. Results: Analysis included 22 RCT comprising 13853 participants and supporting approval for 18 distinct drugs. TD was reported in 2212 (16.0%) participants. Among these participants, the leading causes of TD were withdrawal of consent (27.8%), site termination (20.7%), adverse events (17.2%), and loss of follow-up (10.9%). There was a statistically significant imbalance in the experimental arm in 4 RCT (18%) (Table), which was observed for everolimus, ribociclib (with fulvestrant), alpelisib, and neratinib. The OR for TD showed quantitative, but not statistically significant negative association with the ratio of the HR for PFS/OS (Beta -0.393; p=0.18). Conclusions: TD without PD, death, or completion of treatment occurs in a substantial proportion of participants of several RCT supporting approval of drugs for advanced breast cancer. all the statistically significant imbalanced TD in the RCT were in experimental arms. Quantitative association between imbalanced TD and the ratio of HR for PFS/OS suggests imbalanced TD may impact ability to translate improvements in PFS to OS. Results of RCT with imbalance in TD should be interpreted cautiously. [Table: see text]

Interventions to support parents and carers of young people with mental health difficulties: a systematic review protocol

IntroductionGlobally, 8%–14% of children and young people (CYP) have a diagnosable mental health condition, many of whom receive no formal interventions. Parents/carers of CYP experience stress and distress owing to...

Assessing the Robustness of Positive Vascular Surgery Randomized Controlled Trials Using Their Fragility Index

The fragility index (FI) measures the robustness of statistically significant findings in randomized controlled trials (RCTs) calculated as the minimum number of event conversions required to alter the result’s statistical significance. In vascular surgery, many clinical guidelines and critical decision-making points are informed by a handful of key RCTs, especially regarding open surgical vs endovascular treatment. The objective of this study is to evaluate the FI of RCTs with statistically significant primary outcomes that compared open vs endovascular surgery. MEDLINE, Embase, and CENTRAL were searched for RCTs comparing open vs endovascular treatments for abdominal aortic aneurysms, carotid artery stenosis, and peripheral arterial disease to December 2022. RCTs with statistically significant primary dichotomous outcomes were included. Data screening and extraction were conducted in duplicate. The FI was calculated by adding an event to the group with the smaller number of events while subtracting a nonevent to the same group until the Fisher exact test produced a non-statistically significant result (P > .05, Table I). The primary outcome measures were FI and proportion of outcomes where loss to follow-up was greater than FI. Secondary analyses were performed to determine whether FI varied by study disease state, presence of commercial funding, and study design. Overall, 5133 articles were captured in the initial search with 21 RCTs reporting 23 primary outcomes being included in the final analysis. The median FI [first quartile, third quartile] was 3 [3, 20] with 16 outcomes (70%) reporting loss to follow-up greater than its FI. The Mann-Whitney U test revealed that commercially funded RCTs and composite outcomes had greater FIs (20 vs 3, P = .035; 21 vs 3, P = .01, respectively). The FI did not vary between disease states (P = .285) or between index trials vs follow-up analyses (P = .147, Table II). There were significant correlations between FI and P value (Pearson r = 0.901, P < .001) and number of events (r = 0.832, P < .001). A small number of event conversions (median 3) are needed to alter the statistical significance of primary outcomes in vascular surgery RCTs evaluating open surgical and endovascular treatments. Most studies had loss to follow-up greater than its FI, which can call into question trial results, and commercially funded studies had a greater FI. The FI and these findings should be considered in future trial design in vascular surgery.Table ITwo-by-two contingency tables highlighting the calculation of the fragility index (FI), with the FI calculated (FI = 70) for the BEST-CLI trial as an exampleTrial 2 × 2 contingency tableCalculation of the FIEventNo eventEventNo eventOpen surgical treatmentABOpen surgical treatmentA + FIB − FIEndovascular treatmentCDEndovascular treatmentCDFisher exact test: P < .05Fisher exact test: P ≥ .05BEST-CLI 2 × 2 contingency tableCalculation of the FI in the BEST-CLI trialMajor adverse limb event or deathNo eventMajor adverse limb event or deathNo eventBypass with single segment great saphenous vein302416Open surgical treatment372 (302 + 70)346 (416 − 70)Endovascular treatment408308Endovascular treatment408308Fisher exact test: P < .05 (P = .00000002)Fisher exact test: P ≥ .05 (P = .05002)BEST-CLI, Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia. Open table in a new tab Table IICharacteristics of the fragility index (FI) of primary outcomes of statistically significant RCTs evaluating open vs endovascular treatment in vascular surgeryCategoryOutcomes, nMedian FI [Q1, Q3]Disease state AAA103 [3, 3] CAS910 [3, 20] PAD415 [5, 46]Study design Index trial133 [3, 4] Follow-up study1014 [3, 21]Funding Commerciala920 [5, 25] Noncommercial143 [2, 6]Outcome Single163 [2, 9] Compositea721 [8, 38]Loss to follow-up <FI73 [3, 8] ≥FI1616 [6, 2, 21]AAA, Abdominal aortic aneurysm; CAS, carotid artery stenting; PAD, peripheral arterial disease.aP < .05. Open table in a new tab

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial

BackgroundThe aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT).MethodsPrior to RCT, the effect of trehalose (5–20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions.ResultsIn the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05).ConclusionsThe 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

Pilot randomized controlled trial of a hospital-based substance use treatment and recovery team (START) to improve initiation of medication for alcohol or opioid use disorder and linkage to follow-up care

ObjectivesWe conducted a pilot randomized controlled trial (RCT) to explore whether a hospital inpatient addiction consult team (Substance Use Treatment and Recovery Team [START]) based on collaborative care was feasible, acceptable to patients, and whether it could improve uptake of medication in the hospital and linkage to care after discharge, as well as reduce substance use and hospital readmission. The START consisted of an addiction medicine specialist and care manager who implemented a motivational and discharge planning intervention. MethodsWe randomized inpatients age ≥ 18 with a probable alcohol or opioid use disorder to receive START or usual care. We assessed feasibility and acceptability of START and the RCT, and we conducted an intent-to-treat analysis on data from the electronic medical record and patient interviews at baseline and 1-month postdischarge. The study compared RCT outcomes (medication for alcohol or opioid use disorder, linkage to follow-up care after discharge, substance use, hospital readmission) between arms by fitting logistic and linear regression models. FindingsOf 38 START patients, 97 % met with the addiction medicine specialist and care manager; 89 % received ≥8 of 10 intervention components. All patients receiving START found it to be somewhat or very acceptable. START patients had higher odds of initiating medication during the inpatient stay (OR 6.26, 95 % CI = 2.38–16.48, p < .001) and being linked to follow-up care (OR 5.76, 95 % CI = 1.86–17.86, p < .01) compared to usual care patients (N = 50). The study found no significant differences between groups in drinking or opioid use; patients in both groups reported using fewer substances at the 1-month follow-up. ConclusionsPilot data suggest START and RCT implementation are feasible and acceptable and that START may facilitate medication initiation and linkage to follow-up for inpatients with an alcohol or opioid use disorder. A larger trial should assess effectiveness, covariates, and moderators of intervention effects.

Historical Review of the Use of Relative Risk Statistics in the Portrayal of the Purported Hazards of High LDL Cholesterol and the Benefits of Lipid-Lowering Therapy.

The manner in which clinical trial investigators present their findings to healthcare providers and the public can have a substantial influence on their impact. For example, if a heart attack occurs in 2% of those in the placebo group and in 1% of those in the drug-treated group, the benefit to the treated population is only one percentage point better than no treatment. This finding is unlikely to generate much enthusiasm from the study sponsors and in the reporting of the findings to the public. Instead, trial directors can amplify the magnitude of the appearance of the treatment benefit by using the relative risk (RR) value of a 50% reduction of the risk of a heart attack, since one is 50% of two. By using the RR type of data analysis, clinical trial directors can promote the outcome of their trial in their publication and to the media as highly successfulwhile minimizing or disregarding entirelythe absolute risk (AR) reduction of only one percentage point. The practice of expressing the RR without the AR has become routinely deployed in the reporting of findings in many different areas of clinical research. We have provided a historical perspective on how this form of data presentation has become commonplace in the reporting of findings from randomized controlled trials (RCTs) on coronary heart disease (CHD) event monitoring and prevention over the past four decades. We assert that the emphasis on RR coupled with insufficient disclosure of AR in the reporting of RCT outcomes has led healthcare providers and the public to overestimate concerns about high cholesterol and to be misled as to the magnitude of the benefits of cholesterol-lowering therapy. The goal of this review is to prompt the scientific community to address this misleading approach to data presentation.

The reverse fragility index: RCTs reporting non-significant differences in failure rates between hamstring and bone-patellar tendon-bone autografts have fragile results.

The reverse fragility index (RFI) is a novel metric to appraise the results of studies reporting statistically non-significant results. The purpose of this study was to determine the statistical robustness of randomized controlled trials (RCTs) reporting non-significant differences in anterior cruciate ligament reconstruction (ACLR) graft failure rates, defined as re-rupture/revision ACLR rate, between hamstring tendon (HT) and bone-patellar tendon-bone (BTB) autografts by calculating RFIs. A systematic review was performed to identify RCTs that compared HT to BTB grafts for ACLR through January 2022. Studies reporting non-significant differences in graft re-rupture and revision ACLR rate (n.s.) were included. The RFI, defined as the fewest number of event reversals needed to change the non-significant graft re-rupture/revision outcome to statistically significant (P < 0.05), was recorded for each study. In addition, the number of studies in which the loss to follow-up exceeded the RFI was recorded. Among the 16 included RCTs, the median (interquartile range [IQR]) sample size was 71 (64-114), and the median (IQR) total number of graft re-rupture/revision ACLR events was 4 (4-6). The median (IQR) graft re-rupture/revision ACLR rate was 4.3% (3.0-6.4) overall, 4.1% (2.6-6.7) in the BTB group, and 5.4% (3.0-6.3) in the HT group. The median (IQR) RFI was 3 (3-4), signifying that a reversal of the outcome in 3 patients in one arm was needed to flip the studies' result from non-significant to statistically significant (P < 0.05). The median (IQR) number of participants lost to follow-up was 11 (3-13), and 13 (81.3%) of the included studies had a loss to follow-up greater than the studies' RFI. The results of RCTs reporting statistically non-significant re-rupture/revision ACLR rates between HT and BTB autografts would become significant if the outcome were reversed in a small number of patients-a number that was less than the loss to follow-up in the majority of studies. Thus, the neutrality of these studies is fragile, and a true statistically significant difference in re-rupture/revision rates may have been undetected. Level I.

The efficacy of sodium ferulate combination therapy in coronary heart disease: A systematic review and meta-analysis

BackgroundSodium ferulate (SF), a derivative of ferulic acid, is one of the active constituents in medicinal plants thought to be useful in fighting cardiovascular diseases. However, there still lacks a systematic review of the efficacy and safety of SF in treating coronary heart disease (CHD). It is therefore the purpose of this study to comprehensively review all clinical randomized controlled trials (RCTs) of SF in CHD to assess its efficacy and safety. MethodsAll analysis is based on 8 databases as of February 2023, which includes 35 outcomes of RCTs that investigate the effect of SF combination therapy in CHD. The present study evaluates the quality and bias of selected literature by the Jadad scale and Cochrane Collaboration's tools, and also the quality of evidence by GRADE Profiler. Furthermore, it applies sensitivity analysis to assess the high heterogeneity impact of outcomes and conducted subgroup analysis to estimate the influence factors in these studies. The study protocol was set documented, and published beforehand in PROSPERO (Registration No.CRD42022348841). ResultsThe meta-analysis of 36 studies (with 3207 patients) shows that SF combined with conventional drugs has improved clinical effectiveness for patients with CHD [RR: 1.21 (95% CI 1.17,1.26); p < 0.00001]. Statistically significant results of meta-analyses are also seen in electrocardiography (ECG) efficacy, frequency of angina attacks, endothelium-dependent flow-mediated vasodilation (FMD), nitric oxide (NO), endothelin (ET), whole Blood low shear rate (LS), platelet aggregation test (PAgT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL6), triglyceride (TG). Adverse events are reported in 6 RCTs. By GRADE approaches, 2 outcomes (clinical efficacy, CRP) indicate a moderate quality of evidence, 17 outcomes indicate low quality of evidence, with the other 16 very low-quality. ConclusionSF combination therapy has a better curative effect than conventional therapy. However, due to items with low-quality evidence demonstrated in the study, the presence of clinical heterogeneity, and imprecision in partial outcome measures, all these led to limitations in the evidence of this study. Thus, the conclusion needs to be further verified by more in-depth research.

A Core Outcome Set for nutritional intervention studies in older adults with malnutrition and those at risk: a study protocol

BackgroundMalnutrition (i.e., protein-energy malnutrition) in older adults has severe negative clinical consequences, emphasizing the need for effective treatments. Many, often small, randomized controlled trials (RCTs) testing the effectiveness of nutritional interventions for the treatment of malnutrition showed mixed results and a need for meta-analyses and data pooling has been expressed. However, evidence synthesis is hampered by the wide variety of outcomes and their method of assessment in previous RCTs. This paper describes the protocol for developing a Core Outcome Set (COS) for nutritional intervention studies in older adults with malnutrition and those at risk.MethodsThe project consists of five phases. The first phase consists of a scoping review to identify frequently used outcomes in published RCTs and select additional patient-reported outcomes. The second phase includes a modified Delphi Survey involving experienced researchers and health care professionals working in the field of malnutrition in older adults, followed by the third phase consisting of a consensus meeting to discuss and agree what critical outcomes need to be included in the COS. The fourth phase will determine how each COS outcome should be measured based on a systematic literature review and a second consensus meeting. This will be followed by a dissemination and implementation phase. Patient and Public Involvement (PPI) representatives will contribute to study design, oversight, consensus, and dissemination.ConclusionsThe result of this project is a COS that should be included in any RCT evaluating the effect of nutritional interventions in older adults with malnutrition and those at risk. This COS will facilitate comparison of RCT results, will increase efficient use of research resources and will reduce bias due to measurement of the outcome and publication bias. Ultimately, the COS will support clinical decision making by identifying the most effective approaches for treating and preventing malnutrition in older adults.

Effectiveness and safety of Suhuang Zhike capsule as adjuvant treatment for acute exacerbation of chronic obstructive pulmonary disease: a systematic review and Meta-analysis.

To evaluate the efficacy and safety of Suhuang Zhike capsule in the adjuvant treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The database including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Database, China Science and Technology Journal Database, Chinese Biomedical Literature Database and Wanfang Data was searched. The retrieval time was from database establishment to May 2021. Randomized controlled trial (RCT) of Suhuang zhike capsule adjuvant treatment for AECOPD was included. The quality of the studies was independently evaluated and cross-checked by two reviewers, and Meta-analysis was performed by using RevMan5.3 software. Thirteen RCT results were included with a total sample number of 1195 cases, including 597 in the experimental group and 598 in the control group. The results showed that Suhuang zhike capsule adjuvant treatment of AECOPD could improve the total clinical effect rate compared with conventional treatment. Suhuang zhike capsule adjuvant treatment could improve forced vital capacity (FVC), forced expiratory volume in one second (FEV), FEV/FVC, peak expiratory flow (PEF) and other pulmonary function indexes; decrease C-reactive protein (CRP), white blood cells, neutrophils and other infectious indicators; besides, the 1-year recurrence rate of the disease was decreased (all 0.05). Suhuang Zhike capsule can improve the lung function and clinical efficacy of AECOPD, thus increasing the exercise endurance, and reducing the infection and recurrence rate in AECOPD patients.

Mechanical Circulatory Support Devices in Acute Myocardial Infarction-Cardiogenic Shock: Current Studies and Future Directions.

Cardiogenic shock (CS) caused by acute myocardial infarction (AMI) accounts for most deaths in the population with AMI and continues to be associated with high short-term mortality. Several temporary mechanical circulatory support (MCS) devices have been developed to treat CS and studied in randomized controlled trials (RCTs) of patients with AMI-CS. Unfortunately, none of these RCTs has demonstrated an improvement in survival with temporary MCS in AMI-CS. Potential reasons for these negative results in RCTs are numerous and reflect the challenges of enrolling critically ill patients with CS. Researchers have used observational study designs to provide insights about outcomes associated with the use of temporary MCS in AMI-CS. These observational studies have yielded conflicting results, in some cases contrary to the results of RCTs. Several limitations pertinent to both RCTs and observational analyses, mostly relating to selection bias and failure to consider unmeasured confounding variables and population heterogeneity, preclude drawing strong inferences regarding the effects of temporary MCS on survival in populations with AMI-CS. Understanding these limitations is essential to correctly interpreting the literature regarding temporary MCS to treat AMI-CS and is necessary to inform the design of future studies that will potentially provide stronger evidence. Optimally matching temporary MCS devices to the needs of individual patients with AMI-CS will presumably be more successful than indiscriminate application in unselected patients. In this review, we discuss the existing literature on temporary MCS to treat AMI-CS and describe the specific challenges that must be overcome to develop an improved evidence base for guiding clinical practice.

Reporting quality of abstracts from randomised controlled trials published in leading critical care nursing journals: a methodological quality review

ObjectivesTo evaluate the methodological quality of randomised controlled trial (RCT) abstracts in leading critical care nursing journals against the Consolidated Standards of Reporting Trials-s (CONSORT-A) checklist and to identify variables...

Unblinding and demand characteristics in the treatment of depression

Blinding of treatment allocation in clinical trials in psychiatry is regarded as an ideal. The potential impact of unblinding chimes with a general concern for psychological research: so-called demand characteristics can undermine confidence in findings from experimental and clinical studies. Scepticism can result in nihilism. The reliance on subjective report of symptoms in clinical trials of drug efficacy in depression provides an important example. It is regularly implied that if subjective effects, including specific adverse reactions, unblind participants to an active treatment then evidence for its efficacy is suspect. In fact, the strong association between dose and subjective effects does not translate into a strong relationship with efficacy in randomised controlled trials (RCTs) of conventional antidepressant drugs; this observation falsifies the proposition that unblinding is the principal mechanism driving RCT outcomes in studies of depression. Instead, changes in brain function, that occur soon after treatment starts, do predict treatment outcomes and align with our understanding of neurotransmitter effects from neuroscience. Psychedelic experience for the treatment of depression must be unblinding, but the effect results directly from serotonergic receptor activation and changes in brain connectivity. Where such effects are part of a novel mechanism of action, a strong dose response relationship would be expected, irrespective of unblinding. We highlight the importance of exploring blinding as a mechanism, confirming dose-related outcomes, and dissociating unblinding effects from efficacy. Unblinding does not necessarily invalidate the subjective experience of sustained recovery from depression.