Clustering of EORTC QLQ-C30 health-related quality of life scales across several cancer types: Validation study.

INTRODUCTION: The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) measures 15 health-related quality of life (HRQoL) scales relevant to the disease and treatment of patients with cancer. A study by Martinelli (2011) demonstrated that these scales could be grouped into three main clusters: physical, psychological and gastrointestinal. This study aims to validate Martinelli's findings in an independent dataset and evaluate whether these clusters are consistent across cancer types and patient characteristics. METHODS: Pre-defined criteria for successful validation were three main clusters should emerge with a minimum R-squared value of 0.51 using pooled baseline-data. A cluster analysis was performed on the 15 QLQ-C30 HRQoL-scales in the overall dataset, as well as by cancer type and selected patient characteristics to examine the robustness of the results. RESULTS: The dataset consisted of 20,066 patients pooled across 17 cancer types. Overall, three main clusters were identified (R2 = 0.61); physical-cluster included role-functioning, physical-functioning, social-functioning, fatigue, pain, and global-health status; psychological-cluster included emotional-functioning, cognitive-functioning, and insomnia; gastro-intestinal-cluster included nausea/vomiting and appetite loss. The results were consistent across different levels of disease severity, socio-demographic and clinical characteristics with minor variations by cancer type. Global-health status was found to be strongly linked to the scales included in the physical-functioning-related cluster. CONCLUSION: This study successfully validated prior findings by Martinelli (2011): the QLQ-C30 scales are interrelated and can be grouped into three main clusters. Knowing how these multidimensional HRQoL scales are related to each other can help clinicians and patients with cancer in managing symptom burden, guide policymakers in defining social-support plans and inform selection of HRQoL scales in future clinical trials.

Improving Mental Health Services: A 50-Year Journey from Randomized Experiments to Artificial Intelligence and Precision Mental Health.

This conceptual paper describes the current state of mental health services, identifies critical problems, and suggests how to solve them. I focus on the potential contributions of artificial intelligence and precision mental health to improving mental health services. Toward that end, I draw upon my own research, which has changed over the last half century, to highlight the need to transform the way we conduct mental health services research. I identify exemplars from the emerging literature on artificial intelligence and precision approaches to treatment in which there is an attempt to personalize or fit the treatment to the client in order to produce more effective interventions.

Risk of fatigue and anemia in patients with advanced cancer treated with olaparib: A meta-analysis of randomized controlled trials.

INTRODUCTION: PARP inhibitors are a new class of drugs that are currently being studied in several malignancies. Olaparib is FDA-approved for advanced breast cancer and advanced ovarian cancer patients. Fatigue and anemia are among the most common cancer and treatment-related symptoms. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) to characterize the incidence and relative risks (RRs) of fatigue and anemia associated with olaparib. METHODS: PubMed, Cohrane, Embase and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018. The eligible studies were phase II and III RCT of olaparib. Safety profile from each selected study was evaluated for all-grade and high-grade fatigue and anemia adverse events. Summary incidences and the RR, with 95% confidence intervals, of all-grade and high-grade events were calculated using random-effects or fixed-effects model based on the heterogeneity of selected studies. RESULTS: A total of 9 trials were selected, and included 2074 patients with advanced ovarian, gastric, prostate, lung or breast cancer. 908 patients received placebo/control treatments and 1166 received olaparib alone or combination with other active cancer treatments. The RR of all-grade and high fatigue was 1.24 (95% CI, 1.10-1.39) and 1.71 (95% CI, 1.06-2.77), respectively. The RR of all-grade and high-grade anemia was 2.10 (95% CI, 1.48-2.98) and 3.15 (95% CI, 1.73-5.71), respectively. CONCLUSION: Our findings suggest that the olaparib treatment is associated with an increased risk of fatigue and anemia. Since fatigue and anemia are very common treatment related adverse events, and both can impair the quality of life of patients, it is important to identify them early and manage it accordingly in order to optimize the overall treatment.

Adult Stem Cell Therapy for Cardiac Repair in Patients After Acute Myocardial Infarction Leading to Ischemic Heart Failure: An Overview of Evidence from the Recent Clinical Trials.

BACKGROUND: Cardiovascular diseases (CVD) still represent the leading cause of mortality worldwide, despite the remarkable advances in interventional cardiology, cardiac surgery, and modern pharmacotherapy, particularly in the setting of acute myocardial infarction (AMI), chronic ischemic heart failure (HF), cardiomyopathy (CM), and the associated left ventricular (LV) dysfunction. A significant loss of cardiomyocytes that underlies all of these conditions was previously considered irreversible. However, current evidence indicates that the human heart has some potential for repair, and over the past decade, many research studies have been exploring the use of stem cells (SCs) to facilitate restoration of myocardium. Consequently, the safety, feasibility, and effectiveness of SC therapy have been reported in many randomized clinical trials (RCTs), using different lineages of adult SCs. Nevertheless, the clinical benefits of SC therapy are not yet well established. In the near future, understanding of the complex interrelations between SCs, paracrine factors, genetic or epigenetic predispositions, and myocardial microenvironment, in the context of an individual patient, will be crucial for translation of this knowledge into practical development of successful, long-term regenerative SC therapeutic applications, in a growing population of patients suffering from previous myocardial infarction (MI) leading to chronic ischemic cardiomyopathy. CONCLUSION: This overview highlights the therapeutic potential of adult SCs in terms of their possible regenerative capacity, safety, and clinical outcomes, in patients with AMI, and/or subsequent HF (due to chronic ischemic cardiomyopathy). This review was based upon PubMed database search for trials on SC therapy, in patients with AMI and HF, and the main timeframe was set from 2006 to 2016.

The heart of the matter: Outcome reporting bias and registration status in cardio-thoracic surgery.

BACKGROUND: Our objective is to compare registered outcomes to published reports; to evaluate for discrepancies favoring statistically significant outcomes; to examine funding source and likelihood of outcome reporting bias; and to evaluate for any temporal trends in outcome reporting bias. METHODS: PubMed was searched for randomized controlled trials published between 2008 and 2015 from 4 high impact cardio-thoracic journals: European Journal of Cardio-thoracic Surgery (EJCS), The Journal of Cardiothoracic Surgery (JCS), The Journal of Thoracic and Cardiovascular Surgery (JTCS), and Annals of Cardiothoracic Surgery (ACS). Data was collected using a standardized extraction form. RESULTS: We reviewed 287 articles, of which 214 (74.6%) did not meet registration criteria. Of those 214, 94 (43.9%) were published in the EJCS, 34 (15.9%) in JCS, 86 (40.2%) in JTCS, and 0 (0%) in the ACS. Of the remaining 73 articles, 34 (46.6%) had a discrepancy between the primary outcome registered and the published outcome, and 11 of the 34 reported p-values favoring the change. We also found that 12 of the 73 registrations had updated primary outcomes from the initial report to the final report. The timing of registration was an incidental finding showing 14 (19.1%) articles retrospectively registered, 29 (39.7%) registered during patient enrollment, and 30 (41.1%) registered prospectively. CONCLUSION: The results indicated that selective outcome reporting is prevalent in cardio-thoracic surgery journals. The more concerning issue, however, is the lack of registration or provision of registration number for randomized controlled trials within these journals.

Meta-analysis of Acupuncture as Adjuvant Therapy in Improving Gastrointestinal Function of Acute Pancreatitis Patients / 广州中医药大学学报

Objective To evaluate the clinical effect of acupuncture as an adjuvant therapy for acute pancreatitis (AP).Methods We retrieved the databases ofCNKI,VIP,Wanfang,PubMed,EMBase,and Cochrane Library,selected the relevant randomized clinical trials (RCTs) of AP treated with routine western medicine as control group and treated with routine western medicine combined with acupuncture therapy as trial group.And then,the quality of the qualified RCTs was evaluated,and the end-point outcomes of the RCTs were analyzed by Meta-analysis.Results A total of 7 RCTs involving 371 AP patients were included into the analysis.The time for abdominal pain relief(WMD =-1.44;95％CI:-2.38,-0.50),time for abdominal distension relief (WMD =-2.50;5％CI:-4.07,-0.73),time for the restart of anal exhaust(WMD =-1.79;95％CI:-3.73,-0.14),time for defecation (WMD =-1.95;95％CI:-3.51,-0.39),time for the restart of bowel sound(WMD =-1.39;95％CI:-2.44,-0.34),time for blood amylase becoming normal(WMD =-2.09;95％CI:-3.22,-0.96),and hospitalization time (WMD =-3.70;95％CI:-6.04,-1.36) in the trial group were less than those in the control group,and the differences of the above indexes except for the time for the restart of anal exhaust were significant (P ＜ 0.05).Conclusion Acupuncture as an adjuvant therapy is effective for improving the gastrointestinal function of AP patients,and shortening time for blood amylase becoming normal and hospitalization time.However,due to the low methodological quality,more well-designed randomized controlled trials are needed to confirm the therapeutic effect of acupuncture therapy for AP.

Combining Non-randomized and Randomized Data in Clinical Trials Using Commensurate Priors.

Randomization eliminates selection bias, and attenuates imbalance among study arms with respect to prognostic factors, both known and unknown. Thus, information arising from randomized clinical trials (RCTs) is typically considered the gold standard for comparing therapeutic interventions in confirmatory studies. However, RCTs are limited in contexts wherein patients who are willing to accept a random treatment assignment represent only a subset of the patient population. By contrast, observational studies (OSs) often enroll patient cohorts that better reflect the broader patient population. However, OSs often suffer from selection bias, and may yield invalid treatment comparisons even after adjusting for known confounders. Therefore, combining information acquired from OSs with data from RCTs in research synthesis is often criticized due to the limitations of OSs. In this article, we combine randomized and non-randomized substudy data from FIRST, a recent HIV/AIDS drug trial. We develop hierarchical Bayesian approaches devised to combine data from all sources simultaneously while explicitly accounting for potential discrepancies in the sources' designs. Specifically, we describe a two-step approach combining propensity score matching and Bayesian hierarchical modeling to integrate information from non-randomized studies with data from RCTs, to an extent that depends on the estimated commensurability of the data sources. We investigate our procedure's operating characteristics via simulation. Our findings have implications for HIV/AIDS research, as well as elucidate the extent to which well-designed non-randomized studies can complement RCTs.

Ongoing clinical studies of minimally invasive surgery for gastric cancer in Japan.

Since the development of laparoscopy-assisted distal gastrectomy (LADG) with lymph node dissection for gastric cancer in Japan, this type of surgery is improving and evolving. To establish high-quality evidence of laparoscopic gastrectomy (LAG) in the field of gastric cancer treatments, two large-scale, prospective randomized controlled trials have been performed in Japan; the Japan Clinical Oncology Study Group (JCOG) 0912 for early disease and the Japanese Laparoscopic Surgery Study Group (JLSSG) 0901 for advanced disease. Analyses using mega-data from the National Clinical Database (NCD) have also been carried out as a clinical study to clarify the safety of LAG. Furthermore, as advanced laparoscopic techniques have been developed, prospective clinical studies are being performed with regard to laparoscopy-assisted total gastrectomy (LATG), robotic gastrectomy, and minimally invasive surgery with sentinel node (SN) navigation. This review summarizes the current status of minimally invasive surgeries for gastric cancer based on the latest ongoing clinical trials in Japan.

Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals.

OBJECTIVE: To illustrate the utility of statistical monitoring boundaries in meta-analysis, and provide a framework in which meta-analysis can be interpreted according to the adequacy of sample size. To propose a simple method for determining how many patients need to be randomized in a future trial before a meta-analysis can be deemed conclusive. STUDY DESIGN AND SETTING: Prospective meta-analysis of randomized clinical trials (RCTs) that evaluated the effectiveness of isoniazid chemoprophylaxis versus placebo for preventing the incidence of tuberculosis disease among human immunodeficiency virus (HIV)-positive individuals testing purified protein derivative negative. Assessment of meta-analysis precision using trial sequential analysis (TSA) with LanDeMets monitoring boundaries. Sample size determination for a future trials to make the meta-analysis conclusive according to the thresholds set by the monitoring boundaries. RESULTS: The meta-analysis included nine trials comprising 2,911 trial participants and yielded a relative risk of 0.74 (95% CI, 0.53-1.04, P = 0.082, I(2) = 0%). To deem the meta-analysis conclusive according to the thresholds set by the monitoring boundaries, a future RCT would need to randomize 3,800 participants. CONCLUSION: Statistical monitoring boundaries provide a framework for interpreting meta-analysis according to the adequacy of sample size and project the required sample size for a future RCT to make a meta-analysis conclusive.