Showing papers on "Subgroup analysis published in 2019"
TL;DR: In this article, the authors developed a tutorial with the aim of improving the interpretation of subgroup analyses in reviews, and demonstrated how to interpret subgroup analysis using theoretical examples and a real-life sub-group analysis with clinical context.
234 citations
University of Salford1, University of Manchester2, University of Birmingham3, The Royal Marsden NHS Foundation Trust4, University College London5, Guy's and St Thomas' NHS Foundation Trust6, Institute of Cancer Research7, University of Bern8, University of Glasgow9, Beatson West of Scotland Cancer Centre10, Northampton Community College11, Cardiff University12
TL;DR: Coadministration of abiraterone acetate and prednisolone with androgen deprivation therapy (ADT) is associated with prolonged overall survival and disease control, compared with ADT alone, in all men with metastatic disease starting hormone therapy for the first time.
134 citations
TL;DR: There is high-certainty evidence that providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking increases quit rates and indicates that increasing the amount of behavioural support is likely to increase the chance of success.
Abstract: © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background Pharmacotherapies for smoking cessation increase the likelihood of achieving abstinence in a quit attempt. It is plausible that providing support, or, if support is offered, offering more intensive support or support including particular components may increase abstinence further. Objectives To evaluate the effect of adding or increasing the intensity of behavioural support for people using smoking cessation medications, and to assess whether there are different effects depending on the type of pharmacotherapy, or the amount of support in each condition. We also looked at studies which directly compare behavioural interventions matched for contact time, where pharmacotherapy is provided to both groups (e.g. tests of different components or approaches to behavioural support as an adjunct to pharmacotherapy). Search methods We searched theCochraneTobaccoAddictionGroup SpecialisedRegister, clinicaltrials.gov, and the ICTRP in June 2018 for recordswith any mention of pharmacotherapy, including any type of nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline, that evaluated the addition of personal support or compared two or more intensities of behavioural support. Selection criteria Randomised or quasi-randomised controlled trials in which all participants received pharmacotherapy for smoking cessation and conditions differed by the amount or type of behavioural support. The intervention condition had to involve person-to-person contact (defined as face-to-face or telephone). The control condition could receive less intensive personal contact, a different type of personal contact, written information, or no behavioural support at all.We excluded trials recruiting only pregnant women and trials which did not set out to assess smoking cessation at six months or longer. Data collection and analysis For this update, screening and data extraction followed standard Cochrane methods. The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemicallyvalidated rates, if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a random-effects model.Main results Eighty-three studies, 36 of which were new to this update, met the inclusion criteria, representing 29,536 participants. Overall, we judged 16 studies to be at low risk of bias and 21 studies to be at high risk of bias. All other studies were judged to be at unclear risk of bias. Results were not sensitive to the exclusion of studies at high risk of bias. We pooled all studies comparing more versus less support in the main analysis. Findings demonstrated a benefit of behavioural support in addition to pharmacotherapy. When all studies of additional behavioural therapy were pooled, there was evidence of a statistically significant benefit from additional support (RR 1.15, 95% CI 1.08 to 1.22, I� = 8%, 65 studies, n = 23,331) for abstinence at longest follow-up, and this effect was not different when we compared subgroups by type of pharmacotherapy or intensity of contact. This effect was similar in the subgroup of eight studies in which the control group received no behavioural support (RR 1.20, 95% CI 1.02 to 1.43, I2 = 20%, n = 4,018). Seventeen studies compared interventions matched for contact time but that differed in terms of the behavioural components or approaches employed. Of the 15 comparisons, all had small numbers of participants and events. Only one detected a statistically significant effect, favouring a health education approach (which the authors described as standard counselling containing information and advice) over motivational interviewing approach (RR 0.56, 95% CI 0.33 to 0.94, n = 378). Authors' conclusions There is high-certainty evidence that providing behavioural support in person or via telephone for people using pharmacotherapy to stop smoking increases quit rates. Increasing the amount of behavioural support is likely to increase the chance of success by about 10% to 20%, based on a pooled estimate from 65 trials. Subgroup analysis suggests that the incremental benefit from more support is similar over a range of levels of baseline support.More research is needed to assess the effectiveness of specific components that comprise behavioural support.
97 citations
TL;DR: Global prevalence of COPD among men is about 5% higher than among women, and the most prevalent stage of COPd is stage 1.
Abstract: Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Aims: To synthesize data on the worldwide prevalence and severity of COPD by geographical region, age groups, and smoking status in a systematic review. Methods: A systematic search was performed following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. International databases including PubMed, Scopus and Web of Science were searched for population-based studies published between January 2004 and May 2015 that reported the prevalence of COPD anywhere in the world. The prevalence of COPD was calculated based on World Health Organization (WHO) regions and sex and severity stages using metaprop. Meta-regression and subgroup analysis were applied to determine the sources of heterogeneity. Results: Sixty papers were screened with a combined subject sample size of 127 598. The prevalence of post-bronchodilator COPD was 12.16 (10.91–13.40). The pooled prevalence of COPD was 15.70 (13.80–18.59) in men and 9.93 (8.73– 11.13) in women. Among all WHO regions, the highest prevalence was recorded in the Region of the Americas (14.53), and the lowest was recorded in the South-East Asia Region/Western Pacific Region (8.80). Meta-regression model variables were: sample size, WHO region, study quality score, level of gathering data, publication year, and sampling methods that justified 29.82 of heterogeneity detected among COPD prevalence rates worldwide. Conclusions: Global prevalence of COPD among men is about 5 higher than among women. The most prevalent stage of COPD is stage 1. © World Health Organization (WHO) 2019.
95 citations
TL;DR: Subgroup analysis revealed that survival rates varied in different World Health Organization regions, age and stage at diagnosis, year of the studies, and degree of development of countries, as well as potential sources of heterogeneity.
80 citations
TL;DR: It seems that adults in food-insecure households, especially women, are at higher risk of obesity, and the weight abnormality risk may increase with the intensification of the level of food insecurity.
Abstract: Research into the relationship between food insecurity and weight abnormality has yielded varied and contradictory results. Therefore, a systematic review and meta-analysis were carried out to examine the association between food insecurity and weight abnormality in adults. Pertinent studies were identified by searching PubMed and Scopus databases, up to February 2018. Data were available from 31 studies. These studies were conducted in 14 different countries. The odds ratio of 115,993 individuals in these studies was pooled for the meta-analysis. The present meta-analysis showed that adults in food-insecure households are more at risk of obesity (OR 1.15, 95% CI 1.06–1.23). Subgroup analysis by gender also revealed that women had a higher risk of obesity compared to men in food-insecure households (OR 1.26, 95% CI 1.05–1.46). Furthermore, subgroup analysis by food insecurity level implied that a severe level of household food insecurity may be associated with a higher risk of underweight (49%) than overweight (37%) or obesity (29%) among adults. In addition, subgroup analysis revealed that with lower levels of national economic development, the risk of weight abnormality shifted from obesity to underweight. It seems that adults in food-insecure households, especially women, are at higher risk of obesity. The weight abnormality risk may increase with the intensification of the level of food insecurity. Also, the level of economic development is an important factor in the effects of food insecurity on weight status. However, due to the high heterogeneity among studies, the results should be interpreted with caution.
78 citations
TL;DR: PR confers significant, clinically relevant benefits on anxiety and depression symptoms in people with COPD, and robust estimates of treatment effects are likely to endure.
74 citations
TL;DR: Based on studies with moderate to high quality, DMT is an effective intervention in the treatment of adults with depression, and will have relevance to both policy-making and clinical practice, and become a platform for further research.
Abstract: Background: Depression is the largest cause of mental ill health worldwide. Although interventions such as Dance Movement Therapy (DMT) may offer interesting and acceptable treatment options, current clinical guidelines do not include these interventions in their recommendations mainly because of what is perceived as insufficient research evidence. The 2015 Cochrane review on DMT for depression includes only three RCTs leading to inconclusive results. It is therefore, necessary to also look beyond such designs in order to identify and assess the range of current evidence. Methods: We therefore, conducted a systematic review of studies that aimed to explore the effectiveness in the use of DMT with people with depression. This led to a qualitative narrative synthesis followed by a subgroup analysis and a sensitivity analysis. In all meta-analyses a random effects model was used with Standardised Mean Differences (SMD) to accommodate for the heterogeneity of studies and outcome measures. Results: From the 817 studies reviewed, eight studies met our inclusion criteria. 351 people with depression (mild to severe) participated, 192 of whom attended DMT groups while receiving treatment as usual (TAU) and 159 received TAU only. Qualitative findings suggest there was a decrease in depression scores in favour of DMT groups in all studies. Subgroup analysis performed on depression scores before and three months after the completion of DMT groups suggested changes in favour of the DMT groups. When sensitivity analysis was performed, RCTs at high risk of bias were excluded, leaving only studies with adult clients up to the age of 65. In these studies, the highest effect size was found favouring DMT plus TAU for adults with depression, when compared to TAU only. Conclusions: Based on studies with moderate to high quality, we concluded that DMT is an effective intervention in the treatment of depression with adults. Furthermore, by drawing on a wide range of designs with diverse quality, we were able to compile a comprehensive picture of relevant trends. Despite the fact that there remains a paucity of high-quality studies, the results have relevance to both policy-making and clinical practice, and become a platform for further research.
70 citations
TL;DR: The authors' findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds.
Abstract: Summary Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627. Findings Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05). Interpretation Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision. Funding British Heart Foundation.
68 citations
TL;DR: There is no association between NSAIDs and the risk of Parkinson disease at the population level, and clinicians need to be vigilant ensuring that the use of NSAIDs remains restricted to their approved anti-inflammatory and analgesic effect.
Abstract: Several studies have explored the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). However, the extent to which NSAIDs may increase or decrease the risk of PD remains unresolved. We, therefore, performed a meta-analysis of relevant studies to quantify the magnitude of the association between NSAID use and PD risk in the elderly population. The electronic databases such as PubMed, EMBASE, Scopus, Google Scholar, and Web of Science were used to search the relevant articles published between January 1990 and December 2017. Large (n ≥ 1000) observational design studies with a follow-up at least 1 year were considered. Two authors independently extracted information from the included studies. Random effect model was used to calculate risk ratios (RRs) with 95% confidence interval (Cl). A total of 17 studies with 2,498,258 participants and nearly 14,713 PD patients were included in the final analysis. The overall pooled RR of PD was 0.95 (95%CI 0.860–1.048) with significant heterogeneity (I2 = 63.093, Q = 43.352, p < 0.0001). In the subgroup analysis, the overall pooled RR of PD was 0.90 (95%CI 0.738–1.109), 0.96 (95%CI 0.882–1.055), and 0.99 (95%CI 0.841–0.982) from the studies of North America, Europe, and Asia. Additionally, long-term use, study design, individual NSAID use, and risk of PD were also evaluated. Despite the neuroprotective potential of NSAIDs demonstrated in some experimental studies, our findings suggest that there is no association between NSAIDs and the risk of Parkinson disease at the population level. Until further evidence is established, clinicians need to be vigilant ensuring that the use of NSAIDs remains restricted to their approved anti-inflammatory and analgesic effect.
66 citations
TL;DR: In this meta-analysis, despite its use in different patient populations, the troponin type used, timeline of follow-up, a low-risk HEART score had high sensitivity, negative predictive value, and negative likelihood ratio for predicting short-term major adverse cardiac events, although risk of bias and statistical heterogeneity were high.
TL;DR: Mind-body exercises were found to have significant improvements in motor function, depressive symptoms, and quality of life in patients with Parkinson’s disease, and can be used as an effective method for clinical exercise intervention in PD patients.
Abstract: Purpose: To systematically evaluate the effects of mind-body exercises (Tai Chi, Yoga, and Health Qigong) on motor function (UPDRS, Timed-Up-and-Go, Balance), depressive symptoms, and quality of life (QoL) of Parkinson’s patients (PD). Methods: Through computer system search and manual retrieval, PubMed, Web of Science, The Cochrane Library, CNKI, Wanfang Database, and CQVIP were used. Articles were retrieved up to the published date of June 30, 2019. Following the Cochrane Collaboration System Evaluation Manual (version 5.1.0), two researchers independently evaluated the quality and bias risk of each article, including 22 evaluated articles. The Pedro quality score of 6 points or more was found for 86% (19/22) of these studies, of which 21 were randomized controlled trials with a total of 1199 subjects; and the trial intervention time ranged from 4 to 24 weeks. Interventions in the control group included no-intervention controls, placebo, waiting-lists, routine care, and non-sports controls. Meta-analysis was performed on the literature using RevMan 5.3 statistical software, and heterogeneity analysis was performed using Stata 14.0 software. Results: (1) Mind-body exercises significantly improved motor function in PD patients, including UPDRS (SMD = −0.61, p < 0.001), TUG (SMD = −1.47, p < 0.001) and balance function (SMD = 0.79, p < 0.001). (2) Mind-body exercises also had significant effects on depression (SMD = −1.61, p = 0.002) and QoL (SMD = 0.66, p < 0.001). (3) Among the indicators, UPDRS (I2 = 81%) and depression (I2 = 91%) had higher heterogeneity; according to the results of the separate combined effect sizes of TUG (I2 = 29%), Balance (I2 = 16%) and QoL (I2 = 35%), it shows that the heterogeneity is small; (4) After meta-regression analysis of the age limit and other possible confounding factors, further subgroup analysis showed that the reason for the heterogeneity of UPDRS motor function may be related to the sex of PD patients and severity of the disease; the outcome of depression was heterogeneous. The reason for this may be the use of specific drugs in the experiment and the duration of intervention in the trial. Conclusion: (1) Mind-body exercises were found to have significant improvements in motor function, depressive symptoms, and quality of life in patients with Parkinson’s disease, and can be used as an effective method for clinical exercise intervention in PD patients. (2) Future clinical intervention programs for PD patients need to fully consider specific factors such as gender, severity of disease, specific drug use, and intervention cycle to effectively control heterogeneity factors, so that the clinical exercise intervention program for PD patients is objective, scientific, and effective.
TL;DR: High concentrations of air pollution were significantly related to the higher risk of adverse birth outcomes, however, the sources of heterogeneity among studies should be further explored.
Abstract: Several reviews have assessed the relationship between exposure to ambient air pollution and adverse birth outcomes during pregnancy, but the results remain controversial. The objective of this study was to assess this correlation quantitatively and to explore sources of heterogeneity. We included all published case-control or cohort studies that evaluated the correlation between ambient air pollution and low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA). Analytical methods and inclusion criteria were provided on the PROSPERO website (CRD42018085816). We evaluated pooled effects and heterogeneity. Subgroup analyses (grouped by exposure period, study settings, study design, exposure types, data source, Newcastle-Ottawa quality score (NOS), and adjustment for smoking or meteorological factors) were also conducted and publication bias was examined. The risk of bias in systematic reviews (ROBIS) tool was used to evaluate the overall risk of bias in this review. Forty studies met the inclusion criteria. We observed pooled odds ratios (ORs) of 1.03-1.21 for LBW and 0.97-1.06 for PTB when mothers were exposed to CO, NO2, NOx, O3, PM2.5, PM10, or SO2 throughout their pregnancy. For SGA, the pooled estimate was 1.02 in relation to NO2 concentrations. Subgroup analysis and sensitivity analysis decreased the heterogeneity to some extent, such as the subgroups of continuous measures (OR=0.98 (0.97-0.99), I2=0.0%) and NOS>7 (OR=0.98 (0.97-0.99), I2=0.0%) in evaluating the association between PTB and NO2. This review was completed with a low risk of bias. High concentrations of air pollution were significantly related to the higher risk of adverse birth outcomes. However, the sources of heterogeneity among studies should be further explored.
TL;DR: This work aimed to identify modifiable risk factors for PD with cognitive impairment by identifying modifiablerisk factors that can be measured and controlled for in Parkinson's disease.
Abstract: Background Cognitive impairment is a common and devastating manifestation in Parkinson's disease (PD). We aimed to identify modifiable risk factors for PD with cognitive impairment. Methods We systematically searched PubMed and the Cochrane Library from June 1937 to September 2018 and included prospective cohort studies with random-effects model used to combine estimates. Primary analyses for all types of cognitive impairments and subgroup analyses for separate outcomes were conducted. Results A total of 31,298 articles were identified, of which 32 articles with 18 factors met the inclusion criteria for meta-analysis. In the primary analysis, 9 modifiable risk factors were found to increase the risk of PD with cognitive impairment, including postural-instability-gait disorder (relative risk = 3.76, 95% confidence interval = 1.36-10.40), hallucinations (relative risk = 3.09, 95% confidence interval = 1.61-5.93), orthostatic hypotension (relative risk = 2.98, 95% confidence interval = 1.41-6.28), cerebrovascular disease (relative risk = 1.52, 95% confidence interval = 1.01-2.28), diabetes mellitus (relative risk = 1.47, 95% confidence interval = 1.13-1.92), obesity (relative risk = 1.38, 95% confidence interval = 1.15-1.65), cardiac disease (relative risk = 1.35, 95% confidence interval = 1.17-1.56), alcohol consumption (relative risk = 1.32, 95% confidence interval = 1.15-1.52), and smoking (relative risk = 1.31, 95% confidence interval = 1.14-1.50). In the subgroup analysis, postural-instability-gait disorder subtype, orthostatic hypotension and hallucinations may increase the risk of dementia in PD. A total of 37 articles were included in the systematic review, in which 9 risk factors and 1 protective factor were additionally associated in single studies with the risk of PD with cognitive impairment, and 5 factors were associated with specific cognition domains. Conclusions Effective interventions in the management of PD symptoms, comorbidities, and lifestyles may be promising to reduce PD with cognitive impairment risk. © 2019 International Parkinson and Movement Disorder Society.
TL;DR: It is supported that eGFR decline observed with intensive BP goals in ACCORD participants may predominantly reflect hemodynamic alterations, and among a subset of ACCORD trial participants, intensive BP control was associated with reductions in eG FRs, but not with an increase in injury marker levels.
TL;DR: The aim of this study was to assess the real‐world cardiovascular disease (CVD) risk associated with tocilizumab, the first anti–IL‐6R medication approved for the treatment of RA.
Abstract: Objective Multiple studies have shown seemingly unfavorable changes in lipid profiles associated with interleukin-6 receptor (IL-6R) antagonists and some other therapies for rheumatoid arthritis. The aim of this study was to assess the real-world cardiovascular disease (CVD) risk associated with tocilizumab, the first anti-IL-6R medication approved for the treatment of RA. Methods We conducted a cohort study using 2006-2015 Medicare and MarketScan claims for patients with RA in whom treatment with biologic disease-modifying antirheumatic drugs was initiated after January 1, 2010. The primary outcome was a composite of myocardial infarction, stroke, and fatal CVD, assessed using a validated method. The influence of potential confounding due to RA disease activity was assessed in a subgroup analysis (~5-10% of biologic therapy initiations) using the multi-biomarker disease activity (MBDA) score. Results A total of 88,463 patients with RA were included. The crude incidence rate (IR) per 1,000 patient-years for composite CVD events among Medicare patients ranged from 11.8 (95% confidence interval [95% CI] 9.7-14.4) for etanercept users to 17.3 (95% CI 15.2-19.7) for infliximab users. The crude IR for pooled users of a tumor necrosis factor inhibitor was 15.0 (95% CI 13.9-16.3). Compared to tocilizumab, the corresponding adjusted hazard ratios (HRs) were 1.01 (95% CI 0.79-1.28) for abatacept, 1.16 (95% CI 0.89-1.53) for rituximab, 1.10 (95% CI 0.80-1.51) for etanercept, 1.33 (95% CI 0.99-1.80) for adalimumab, and 1.61 (95% CI 1.22-2.12) for infliximab. There were no statistically significant differences in the risk of CVD between tocilizumab and any other biologic when MarketScan data were used. Results were robust in numerous subgroup analyses and after external adjustment to control for RA disease activity in the subgroup of patients with linked MBDA test results (n = 4,156). Conclusion Tocilizumab was associated with a CVD risk comparable to that for etanercept as well as a number of other biologics used for the treatment of RA.
TL;DR: Combination treatment of α-PD-1 and α-CTLA-4 is a feasible strategy with enhanced efficacy and acceptable adverse event and could enhance anti-tumor response in comparison with other treatments, especially for low PD-L1 expression patients undergoing nivolumab treatment.
Abstract: Recently, a series of clinical trials showed that combination of anti-programmed cell death-1 (α-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) could effectively eliminate tumor. However, in comparison with widely adopted mono-immune checkpoint inhibitors, chemotherapy, and targeted therapy, the advantage of combination therapy of α-PD-1 and α-CTLA-4 in response rate and prognosis is controversial especially considering probably increased treatment related adverse event. Thus, we conducted this meta-analysis to explore the efficacy and safety of combination treatment of α-PD-1 and α-CTLA-4. This meta-analysis involved 8 clinical trials. In most trials, the primary endpoint was objective response rate (ORR). Thus we calculated risk ratio (RR) and 95% confidence interval (CI) to compare ORR of patients undergoing different treatment strategies. Moreover, the co-primary endpoints in few trials included progression-free survival and overall survival. Hazard ratio (HR) with 95% CI were employed to weigh the influence of different treatments on prognosis of patients. Subgroup analysis was conducted in patients with high and low expression of PD-L1. Lastly, the safety of combination therapy was evaluated by comparing treatment related adverse events among various treatment groups. Our results showed that ORR was significantly higher in patients receiving α-PD-1 plus α-CTLA-4 compared with α-PD-1 (RR 1.31, 95% CI 1.16–1.48) or α-CTLA-4 monotherapy (RR 2.11, 95% CI 1.84–2.43), chemotherapy and targeted therapy (RR 1.41, 95% CI 1.26–1.58). α-PD-1 plus α-CTLA-4 treated patients had a great advantage on monotherapy, chemotherapy and targeted therapy treated patients in PFS. Notably, no significant alteration in total adverse event rate was observed in α-PD-1 plus α-CTLA-4 treated patients. Results of subgroup analysis showed that combination therapy could enhance anti-tumor response in comparison with other treatments, especially for low PD-L1 expression patients undergoing nivolumab treatment (ORR: RR 1.35, 95% CI 1.11–1.65). Combination treatment of α-PD-1 and α-CTLA-4 is a feasible strategy with enhanced efficacy and acceptable adverse event. Moreover, for some low PD-L1 expression patients, α-CTLA-4 might decrease the risk of resistance to α-PD-1 and demonstrate the synergistic anti-tumor effect.
TL;DR: When the treatment effect on the outcome of interest is influenced by a baseline/demographic factor, investigators say that an interaction is present and this type of analysis is typically referred to as subgroup analysis.
Abstract: Background: When the treatment effect on the outcome of interest is influenced by a baseline/demographic factor, investigators say that an interaction is present. In randomized clinical trials (RCTs), this type of analysis is typically referred to as subgroup analysis. Although interaction (or subgroup) analyses are usually stated as a secondary study objective, it is not uncommon that these results lead to changes in treatment protocols or even modify public health policies. Nonetheless, recent reviews have indicated that their proper assessment, interpretation and reporting remain challenging. Results: Therefore, this article provides an overview of these challenges, to help investigators find the best strategy for application of interaction analyses on binary outcomes in RCTs. Specifically, we discuss the key points of formal interaction testing, including the estimation of both additive and multiplicative interaction effects. We also provide recommendations that, if adhered to, could increase the clarity and the completeness of reports of RCTs. Conclusion: Altogether, this article provides a brief non-statistical guide for clinical investigators on how to perform, interpret and report interaction (subgroup) analyses in RCTs.
TL;DR: Present meta‐analysis suggests that saffron might be beneficial in several outcomes related with cardiovascular disease, however, further RCTs with long term intervention with different dose of administration are needed.
TL;DR: E-health based self-management is effective for cancer-related fatigue and self-efficacy, but not the quality of life, and more high-quality randomized control trials are warranted to confirm these conclusions.
Abstract: Aims To integrate the overall effect of e-health based self-management on cancer-related fatigue (CRF), self-efficacy, and quality of life (QOL) among adult cancer patients. Design A systematic review and meta-analysis of randomized controlled trials. Data sources We researched PubMed, Cumulative Index Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, Web of Science and Embase up to 14 July 2019. Review methods We conducted the review with the Cochrane Handbook (version 5.1.0) and measured the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation criteria. Results Literature searching identified 15 trials with a total of 2,337 participants. Integrated results analysis of e-health based self-management demonstrated a statistically significant but small effect on CRF and self-efficacy, but no statistically significant improvement on the QOL. Meanwhile, subgroup analysis indicated that e-health based self-management had a larger effect on fatigue compared with usual care/waiting list control. Conclusion E-health based self-management is effective for CRF and self-efficacy, but not the QOL. More high-quality randomized control trials are warranted to confirm these conclusions. Impact Results showed e-health could improve fatigue and self-efficacy but not the QOL. Health providers could take into the various factors of e-health interventions when providing telehealth service. Other researchers might be inspired by the current review before they begin a study about e-health.
TL;DR: The results suggest that statins are effective in improving depressive symptoms, particularly in those with clinical depression and that they do not worsen depression in non-depressed subjects.
TL;DR: A comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, and Web of Science databases was conducted to identify studies that reported on the use of Forktip and Franseen-tip needles in EUS-FNB of solid organs and compared the pooled rates of diagnostic-yield.
Abstract: Franseen-tip and Fork-tip needles have been widely used in EUS guided fine-needle biopsy (FNB) of solid organs. There is conflicting data on the performance of these needles and unanswered questions on the ideal number of needle-passes and the requirement of an onsite cytopathologist (ROSE). We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, and Web of Science databases (from inception through July 2018) to identify studies that reported on the use of Forktip and Franseen-tip needles in EUS-FNB of solid organs. The primary outcome was to estimate and compare the pooled rates of diagnostic-yield. A subgroup analysis compared the outcomes based on the number of needle-passes and the availability of ROSE. A total of 23 study-arms were available for analysis. The pooled rate of diagnostic yield with Fork-tip needle was 92.8% (95% CI 85.3 - 96.6, I2 = 73.1) and the pooled rate of diagnostic yield with Franseen-tip needle was 92.7% (95% CI 86.4 - 96.2, I2 = 88.4).
TL;DR: A benefit of acupuncture for IVF outcomes in women with a history of unsuccessful IVF attempt is found, and number of acupuncture treatments is a potential influential factor, given the poor reporting and methodological flaws of existing studies.
Abstract: The effects of acupuncture on in vitro fertilization (IVF) outcomes remain controversial. And the variation in participant, interventions, outcomes studied, and trial design may relate to the efficacy of adjuvant acupuncture. We searched digital databases for relevant studies, including Embase, PubMed, Cochrane Library and some Chinese databases up to December 2018, for randomized controlled trials (RCTs) evaluating the effects of acupuncture on women undergoing IVF. We included studies with intervention groups using needling, and control groups consisting of no acupuncture or sham (placebo) acupuncture. Primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Meta-regression and subgroup analysis were conducted on the basis of eight pre-specified covariates to investigate the variances of the effects of adjuvant acupuncture on pregnancy rates and the sources of heterogeneity. Twenty-seven studies with 6116 participants were included. The pooled clinical pregnancy rate (CPR) from all of acupuncture groups was significantly greater than that of control groups (RR 1.21, 95% CI: 1.07–1.38), whereas the pooled live birth rate (LBR) was not. Meta-regression subgroup analysis showed a more significant benefit of acupuncture for repeated IVF cycle proportion (number of women with a history of prior unsuccessful IVF attempt divided by number of women included in each trial) ≥ 50% group (CPR: RR 1.60, 95% CI: 1.28–2.00; LBR: RR 1.42, 95% CI: 1.05–1.92), and this covariate explained most of the heterogeneity (CPR and LBR: adjusted R2 = 100 and 87.90%). Similar results were found between CPR and number of acupuncture treatments (CPR: p = 0.002, adjusted R2 = 51.90%), but not LBR. Our analysis finds a benefit of acupuncture for IVF outcomes in women with a history of unsuccessful IVF attempt, and number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings.
TL;DR: Exercise is effective and clinically worthwhile in reducing pain immediately post treatment compared to no or minimal interventions in patients with knee OA and adding new data will unlikely change this conclusion.
TL;DR: Integrated tele-monitoring including the delivery of coping skills or education by online methods including pulmonary rehabilitation is recommended to produce significant improvement in quality of life for patients with (very) severe chronic obstructive pulmonary disease.
TL;DR: Subgroup analyses based on types of ICS revealed that fluticasone therapy was associated with an increased risk of pneumonia but not budesonide, and medium- and low-doses of budesonides treatment also did not increase the risk of tuberculosis.
TL;DR: The accuracy of machine learning algorithms for diagnosis of ASD was considered acceptable by few accuracy measures only in cases of sMRI use; however, given the many limitations indicated in the study, further well-designed studies are warranted to extend the potential use of machineLearning algorithms to clinical settings.
Abstract: Background: In the recent years, machine learning algorithms have been more widely and increasingly applied in biomedical fields. In particular, their application has been drawing more attention in the field of psychiatry, for instance, as diagnostic tests/tools for autism spectrum disorder (ASD). However, given their complexity and potential clinical implications, there is an ongoing need for further research on their accuracy.
Objective: This study aimed to perform a systematic review and meta-analysis to summarize the available evidence for the accuracy of machine learning algorithms in diagnosing ASD.
Methods: The following databases were searched on November 28, 2018: MEDLINE, EMBASE, CINAHL Complete (with Open Dissertations), PsycINFO, and Institute of Electrical and Electronics Engineers Xplore Digital Library. Studies that used a machine learning algorithm partially or fully for distinguishing individuals with ASD from control subjects and provided accuracy measures were included in our analysis. The bivariate random effects model was applied to the pooled data in a meta-analysis. A subgroup analysis was used to investigate and resolve the source of heterogeneity between studies. True-positive, false-positive, false-negative, and true-negative values from individual studies were used to calculate the pooled sensitivity and specificity values, draw Summary Receiver Operating Characteristics curves, and obtain the area under the curve (AUC) and partial AUC (pAUC).
Results: A total of 43 studies were included for the final analysis, of which a meta-analysis was performed on 40 studies (53 samples with 12,128 participants). A structural magnetic resonance imaging (sMRI) subgroup meta-analysis (12 samples with 1776 participants) showed a sensitivity of 0.83 (95% CI 0.76-0.89), a specificity of 0.84 (95% CI 0.74-0.91), and AUC/pAUC of 0.90/0.83. A functional magnetic resonance imaging/deep neural network subgroup meta-analysis (5 samples with 1345 participants) showed a sensitivity of 0.69 (95% CI 0.62-0.75), specificity of 0.66 (95% CI 0.61-0.70), and AUC/pAUC of 0.71/0.67.
Conclusions: The accuracy of machine learning algorithms for diagnosis of ASD was considered acceptable by few accuracy measures only in cases of sMRI use; however, given the many limitations indicated in our study, further well-designed studies are warranted to extend the potential use of machine learning algorithms to clinical settings.
Clinical Trial: PROSPERO CRD42018117779; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=117779
TL;DR: The pooled findings indicated that quercetin supplementation did not affect fasting plasma glucose (FPG), homeostasis model of assessment‐estimated insulin resistance, and hemoglobin A1c levels.
Abstract: This systematic review and meta-analysis of randomized controlled trials was performed to determine the effect of quercetin supplementation on glycemic control among patients with metabolic syndrome and related disorders. Databases including PubMed, MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched until August 30, 2018. Nine studies with 10 effect sizes out of 357 selected reports were identified eligible to be included in current meta-analysis. The pooled findings indicated that quercetin supplementation did not affect fasting plasma glucose (FPG), homeostasis model of assessment-estimated insulin resistance, and hemoglobin A1c levels. In subgroup analysis, quercetin supplementation significantly reduced FPG in studies with a duration of ≥8 weeks (weighted mean difference [WMD]: -0.94; 95% confidence interval [CI; -1.81, -0.07]) and used quercetin in dosages of ≥500 mg/day (WMD: -1.08; 95% CI [-2.08, -0.07]). In addition, subgroup analysis revealed a significant reduction in insulin concentrations following supplementation with quercetin in studies that enrolled individuals aged <45 years (WMD: -1.36; 95% CI [-1.76, -0.97]) and that used quercetin in dosages of ≥500 mg/day (WMD: -1.57; 95% CI [-1.98, -1.16]). In summary, subgroup analysis based on duration of ≥8 weeks and used quercetin in dosages of ≥500 mg/day significantly reduced FPG levels.
TL;DR: The meta-analysis showed that outpatient management of acute diverticulitis in an outpatient setting is safe, and the overall failure rate was 4.3% (95% CI 2.6%-6.3%).
Abstract: In Western countries, the incidence of acute diverticulitis (AD) is increasing. Patients with uncomplicated diverticulitis can undergo a standard antibiotic treatment in an outpatient setting. The aim of this systematic review was to assess the safety and efficacy of the management of acute diverticulitis in an outpatient setting. A literature search was performed on PubMed, Scopus, Embase, Central and Web of Science up to September 2018. Studies including patients who had outpatient management of uncomplicated acute diverticulitis were considered. We manually checked the reference lists of all included studies to identify any additional studies. Primary outcome was the overall failure rates in the outpatient setting. The failure of outpatient setting was defined as any emergency hospital admission in patients who had outpatient treatment for AD in the previous 60 days. A subgroup analysis of failure was performed in patients with AD of the left colon, with or without comorbidities, with previous episodes of AD, in patients with diabetes, with different severity of AD (pericolic air and abdominal abscess), with or without antibiotic treatment, with ambulatory versus home care unit follow-up, with or without protocol and where outpatient management is a common practice. The secondary outcome was the rate of emergency surgical treatment or percutaneous drainage in patients who failed outpatient treatment. This systematic review included 21 studies including 1781 patients who had outpatient management of AD including 11 prospective, 9 retrospective and only 1 randomized trial. The meta-analysis showed that outpatient management is safe, and the overall failure rate in an outpatient setting was 4.3% (95% CI 2.6%-6.3%). Localization of diverticulitis is not a selection criterion for an outpatient strategy (p 0.512). The other subgroup analyses did not report any factors that influence the rate of failure: previous episodes of acute diverticulitis (p = 0.163), comorbidities (p = 0.187), pericolic air (p = 0.653), intra-abdominal abscess (p = 0.326), treatment according to a registered protocol (p = 0.078), type of follow-up (p = 0.700), type of antibiotic treatment (p = 0.647) or diabetes (p = 0.610). In patients who failed outpatient treatment, the majority had prolonged antibiotic therapy and only few had percutaneous drainage for an abscess (0.13%) or surgical intervention for perforation (0.06%). These results should be interpreted with some caution because of the low quality of available data. The outpatient management of AD can reduce the rate of emergency hospitalizations. This setting is already part of the common clinical practice of many emergency departments, in which a standardized protocol is followed. The data reported suggest that this management is safe if associated with an accurate selection of patients (40%); but no subgroup analysis demonstrated significant differences between groups (such as comorbidities, previous episode, diabetes). The main limitations of the findings of the present review concern their applicability in common clinical practice as it was impossible to identify strict criteria of failure.
TL;DR: Subgroup analysis suggests that publications exhibiting observed to predicted ICU mortality ratios of greater than 1 before tele-ICU implementation was associated with a reduction inICU mortality after tele- ICU implementation, and future studies should confirm this finding using patient-level data.
Abstract: OBJECTIVES Past studies have examined numerous components of tele-ICU care to decipher which elements increase patient and institutional benefit. These factors include review of the patient chart within 1 hour, frequent collaborative data reviews, mechanisms for rapid laboratory/alert review, and interdisciplinary rounds. Previous meta-analyses have found an overall ICU mortality benefit implementing tele-ICU, however, subgroup analyses found few differences. The purpose of this systematic review and meta-analysis was to explore the effect of tele-ICU implementation with regard to ICU mortality and explore subgroup differences via observed and predicted mortality. DATA SOURCES We searched PubMed, Cochrane Library, Embase, and European Society of Intensive Care Medicine for articles related to tele-ICU from inception to September 18, 2018. STUDY SELECTION We included all trials meeting inclusion criteria which looked at the effect of tele-ICU implementation on ICU mortality. DATA EXTRACTION We abstracted study characteristics, patient characteristics, severity of illness scores, and ICU mortality rates. DATA SYNTHESIS We included 13 studies from 2,766 abstracts identified from our search strategy. The before-after tele-ICU implementation pooled odds ratio for overall ICU mortality was 0.75 (95% CI, 0.65-0.88; p < 0.001). In subgroup analysis, the pooled odds ratio for ICU mortality between the greater than 1 versus less than 1 observed to predicted mortality ratios was 0.64 (95% CI, 0.52-0.77; p < 0.001) and 0.98 (95% CI, 0.81-1.18; p = 0.81), respectively. Test for interaction was significant (p = 0.002). CONCLUSIONS After evaluating all included studies, tele-ICU implementation was associated with an overall reduction in ICU mortality. Subgroup analysis suggests that publications exhibiting observed to predicted ICU mortality ratios of greater than 1 before tele-ICU implementation was associated with a reduction in ICU mortality after tele-ICU implementation. No significant ICU mortality reduction was noted in the subgroup of observed to predicted ICU mortality ratio less than 1 before tele-ICU implementation. Future studies should confirm this finding using patient-level data.