Showing papers on "Subgroup analysis published in 2012"
TL;DR: Supporting self management had no effect on time to first readmission or death with COPD, and a minority of participants who learnt to self manage had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.
Abstract: Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom. Design Randomised controlled trial. Setting Community based intervention in the west of Scotland. Participants Patients admitted to hospital with acute exacerbation of COPD. Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months. Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes. Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions. No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38). Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data. Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables. In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy. Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010). COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003). Conclusion Supported self management had no effect on time to first readmission or death with COPD. Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others. Trial registration Clinical trials NCT 00706303.
226 citations
TL;DR: For patients with a history of myocardial infarction, inhibition of protease-activated receptor 1 with vorapaxar reduces the risk of cardiovascular death or ischaemic events when added to standard antiplatelet treatment, including aspirin, and increases the riskof moderate or severe bleeding.
204 citations
TL;DR: Inhaled steroids reduced admission rates in patients with acute asthma, but it is unclear if there is a benefit of ICS when used in addition to systemic corticosteroids.
Abstract: Background Systemic corticosteroid therapy is central to the management of acute asthma. The use of inhaled corticosteroids (ICS) may also be beneficial in this setting. Objectives To determine the benefit of ICS for the treatment of patients with acute asthma managed in the emergency department (ED). Search methods We identified controlled clinical trials from the Cochrane Airways Group specialised register of controlled trials. Bibliographies from included studies, known reviews, and texts also were searched. The latest search was September 2012. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs. Studies were included if patients presented to the ED or its equivalent with acute asthma, and were treated with ICS or placebo, in addition to standard therapy. Two review authors independently selected potentially relevant articles, and then independently selected articles for inclusion. Methodological quality was independently assessed by two review authors. There were three different types of studies that were included in this review: 1) studies comparing ICS vs. placebo, with no systemic corticosteroids given to either treatment group, 2) studies comparing ICS vs. placebo, with systemic corticosteroids given to both treatment groups, and 3) studies comparing ICS alone versus systemic corticosteroids. For the analysis, the first two types of studies were included as separate subgroups in the primary analysis (ICS vs. placebo), while the third type of study was included in the secondary analysis (ICS vs. systemic corticosteroid). Data collection and analysis Data were extracted independently by two review authors if the authors were unable to verify the validity of extracted information. Missing data were obtained from the authors or calculated from other data presented in the paper. Where appropriate, individual and pooled dichotomous outcomes were reported as odds ratios (OR) with 95% confidence intervals (CIs). Where appropriate, individual and pooled continuous outcomes were reported as mean differences (MD) or standardized mean differences (SMD) with 95% CIs. The primary analysis employed a fixed-effect model and a random-effects model was used for sensitivity analysis. Heterogeneity is reported using I-squared (I2) statistics. Main results Twenty trials were selected for inclusion in the primary analysis (13 paediatric, seven adult), with a total number of 1403 patients. Patients treated with ICS were less likely to be admitted to hospital (OR 0.44; 95% CI 0.31 to 0.62; 12 studies; 960 patients) and heterogeneity (I2 = 27%) was modest. This represents a reduction from 32 to 17 hospital admissions per 100 patients treated with ICS in comparison with placebo. Subgroup analysis of hospital admissions based on concomitant systemic corticosteroid use revealed that both subgroups indicated benefit from ICS in reducing hospital admissions (ICS and systemic corticosteroid versus systemic corticosteroid: OR 0.54; 95% CI 0.36 to 0.81; 5 studies; N = 433; ICS versus placebo: OR 0.27; 95% CI 0.14 to 0.52; 7 studies; N = 527). However, there was moderate heterogeneity in the subgroup using ICS in addition to systemic steroids (I2 = 52%). Patients receiving ICS demonstrated small, significant improvements in peak expiratory flow (PEF: MD 7%; 95% CI 3% to 11%) and forced expiratory volume in one second (FEV1: MD 6%; 95% CI 2% to 10%) at three to four hours post treatment). Only a small number of studies reported these outcomes such that they could be included in the meta-analysis and most of the studies in this comparison did not administer systemic corticosteroids to either treatment group. There was no evidence of significant adverse effects from ICS treatment with regard to tremor or nausea and vomiting. In the secondary analysis of studies comparing ICS alone versus systemic corticosteroid alone, heterogeneity among the studies complicated pooling of data or drawing reliable conclusions. Authors' conclusions ICS therapy reduces hospital admissions in patients with acute asthma who are not treated with oral or intravenous corticosteroids. They may also reduce admissions when they are used in addition to systemic corticosteroids; however, the most recent evidence is conflicting. There is insufficient evidence that ICS therapy results in clinically important changes in pulmonary function or clinical scores when used in acute asthma in addition to systemic corticosteroids. Also, there is insufficient evidence that ICS therapy can be used in place of systemic corticosteroid therapy when treating acute asthma. Further research is needed to clarify the most appropriate drug dosage and delivery device, and to define which patients are most likely to benefit from ICS therapy. Use of similar measures and reporting methods of lung function, and a common, validated, clinical score would be helpful in future versions of this meta-analysis.
196 citations
TL;DR: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third, and eligible trials also showed no significant effect of met formin on all-cause mortality.
Abstract: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I
2statistics for heterogeneity were calculated by fixed effects meta-analysis. Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.
166 citations
TL;DR: Some of the methodological problems with subgroup analysis, and its applicability to considerations of equity, are considered, using both clinical and public health examples, and how policy needs for information on subgroups can be met while maintaining rigour is suggested.
Abstract: The final report from the WHO Commission on the social determinants of health recently noted: ‘For policy, however important an ethical imperative, values alone are insufficient. There needs to be evidence on what can be done and what is likely to work in practice to improve health and reduce health inequities.’ This is challenging, because understanding how to reduce health inequities between the poorest and better-off members of society may require a greater use of subgroup analysis to explore the differential effects of public health interventions. However, while this may produce evidence that is more policy relevant, the requisite subgroup analyses are often seen as tantamount to statistical malpractice. This paper considers some of the methodological problems with subgroup analysis, and its applicability to considerations of equity, using both clinical and public health examples. Finally, it suggests how policy needs for information on subgroups can be met while maintaining rigour.
119 citations
TL;DR: Diabetes increases the risk of breast cancer associated with diabetes in women and supports the hypothesis that diabetes is an independent risk factor for BC.
Abstract: The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13-1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07-1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79-1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99-1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.
113 citations
Queen's University Belfast1, National Institutes of Health2, University of Lübeck3, University of Helsinki4, French Institute of Health and Medical Research5, University of Strasbourg6, University of Toulouse7, Umeå University8, University of Regensburg9, University of Ulm10, University of Leicester11
TL;DR: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.
Abstract: Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design. Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5–18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived. Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50–59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events. Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.
112 citations
Queen's University Belfast1, National Institutes of Health2, University of Lübeck3, University of Helsinki4, French Institute of Health and Medical Research5, University of Strasbourg6, University of Toulouse7, Umeå University8, University of Regensburg9, University of Ulm10, University of Leicester11
TL;DR: In this paper, a multilocus genetic risk score was proposed to refine coronary heart disease (CHD) prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.
Abstract: Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design. Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5–18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived. Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50–59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events. Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.
100 citations
TL;DR: Overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone.
Abstract: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2) positive advanced/metastatic gastric or gastroesophageal junction cancer. ToGA showed that trastuzumab plus chemotherapy (capecitabine/cisplatin or 5-fluorouracil/cisplatin) improved overall survival in the overall population (hazard ratio 0.74). Regional differences in outcome in favor of Japanese populations were observed in other studies; therefore, subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients. We performed subgroup analyses on 101 Japanese patients enrolled into ToGA (trastuzumab plus chemotherapy, n = 51; chemotherapy, n = 50). Median overall survival in the Japanese subgroup was 15.9 months (95% confidence interval 12–25) for trastuzumab plus chemotherapy and 17.7 months (95% confidence interval 12–24) for chemotherapy (hazard ratio 1.00; 95% confidence interval 0.59–1.69). After adjusting for prespecified covariates, the estimated hazard ratio for overall survival was 0.68 (95% confidence interval 0.36–1.27). Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios. After adjusting for imbalanced patient backgrounds between arms, overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone.
97 citations
TL;DR: Although the primary analysis showed no overall benefit, the subgroup analysis suggests that PN may improve satisfaction with care for certain disadvantaged individuals, as well as socially disadvantaged patients who received PN.
Abstract: Background: There is limited high-quality evidence about the impact of patient navigation (PN) on outcomes for patients with diagnosed cancer.
Methods: We pooled data from two sites from the national Patient Navigation Research Program. Patients ( n = 438) with newly diagnosed breast ( n = 353) or colorectal cancer ( n = 85) were randomized to PN or usual care. Trained lay navigators met with patients randomized to PN to help them assess treatment barriers and identify resources to overcome barriers. We used intent-to-treat analysis to assess time to completion of primary treatment, psychologic distress (impact of events scale), and satisfaction (patient satisfaction with cancer-related care) within 3 months after initiation of cancer treatment.
Results: The sample was predominantly middle-aged (mean age = 57) and female (90%); 44% were race-ethnic minorities (44%), 46% reported lower education levels, 18% were uninsured, and 9% reported a non-English primary language. The randomized groups were comparable in baseline characteristics. Primary analysis showed no statistically significant group differences in time to completion of primary cancer treatment, satisfaction with cancer-related care, or psychologic distress. Subgroup analysis showed that socially disadvantaged patients (i.e., uninsured, low English proficiency, and non-English primary language) who received PN reported higher satisfaction than those receiving usual care (all P < 0.05). Navigated patients living alone reported greater distress than those receiving usual care.
Conclusions: Although the primary analysis showed no overall benefit, the subgroup analysis suggests that PN may improve satisfaction with care for certain disadvantaged individuals.
Impact: PN for cancer patients may not necessarily reduce treatment time nor distress. Cancer Epidemiol Biomarkers Prev; 21(10); 1673–81. ©2012 AACR .
86 citations
TL;DR: The evidence of efficacy in the US subgroup suggested that fipamezole at 90 mg TID may be useful to treat LID in PD without exacerbating parkinsonism.
Abstract: Objective: Fipamezole, a selective α 2 -adrenergic receptor antagonist, reduced levodopa-induced dyskinesias (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned monkeys. In 10 dyskinetic subjects with Parkinson disease (PD), a proof-of-concept study showed beneficial effects at single doses of 60 and 90 mg. The primary study objective was to assess suppression of LID by fipamezole at day 28, as measured by the Levodopa-Induced Dyskinesia Scale (LIDS), a modification of the Abnormal Involuntary Movement Scale. Methods: This was a double-blind, randomized, placebo-controlled, dose-escalating 28-day study in levodopa-treated patients with PD experiencing LID, conducted at 25 centers in the United States (115 subjects) and 7 centers in India (64 subjects). Dyskinesias were evaluated 3 times after subjects became “on” from levodopa. Outcome assessment was performed with analysis of variance, which evaluated fipamezole dose-effects in a hierarchical stepwise manner and the Jonckheere test for dose responsiveness. Results: The total study population showed no statistically significant primary endpoint difference. However, because of inhomogeneity recognized between US and Indian study populations, a prespecified subgroup analysis of US subjects was conducted, showing fipamezole at 90 mg reduced LID (mean, 95% CI, LID rating improvement vs placebo −1.9 [0.0 to −3.8; p = 0.047]). Dose responsiveness was demonstrated ( p = 0.014 for placebo, 30, 60, and 90 mg fipamezole). Fipamezole induced mild, transient blood pressure elevation and was associated with an acceptable profile of adverse effects. Conclusions: The evidence of efficacy in the US subgroup suggested that fipamezole at 90 mg TID may be useful to treat LID in PD without exacerbating parkinsonism. Classification of evidence: This study provides Class III evidence that fipamezole is well-tolerated and, in the US subpopulation, lessens LID at 90 mg TID.
TL;DR: An updated meta-analysis of D1 versus D2 randomized controlled trials comparing outcomes found a trend of improved survival exists among D2 patients who did not undergo resection of the spleen or pancreas, as well as for patients with T3/T4 cancers.
Abstract: Surgery is the only curative treatment for patients with gastric cancer. However, the extent of lymph node dissection is still debated. Therefore, with the publication of newer trial results, we conducted an updated meta-analysis of D1 versus D2 randomized controlled trials comparing outcomes. Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985, to December 31, 2010. Meta-analyses were performed using RevMan v5 software. Both short- and long-term outcomes were analyzed. Subgroup analyses of T stage and spleen/pancreas resection versus preservation were performed. Outcomes of 5 randomized trials involving 1642 patients (845 D1, 797 D2) enrolled from 1982 to 2005 were included. Despite the addition of the more recent trials, overall hospital mortality and reoperation rates were still higher in D2 cases. Subgroup analysis of recent trials and spleen/pancreas preservation revealed no significant difference in hospital mortality between groups. Five-year overall survival was similar between D1 versus D2 trials. Sub-analysis by tumor depth and spleen/pancreas preservation detected trends for improved survival with D2 lymphadenectomy in T3/T4 patients and those with spleen/pancreas preservation. Earlier trials show that D2 dissections have higher operative mortality, while recent trials have similar rates. A trend of improved survival exists among D2 patients who did not undergo resection of the spleen or pancreas, as well as for patients with T3/T4 cancers.
TL;DR: Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide, with no treatment-by-subgroup interaction test reaching statistical significance.
Abstract: Background: The Teriflunomide Multiple Sclerosis Oral (TEMSO) trial, a randomized, double-blind, placebo-controlled phase III study, demonstrated that teriflunomide significantly reduced annualized relapse rate (ARR), disease progression and magnetic resonance imaging (MRI) activity, with a favorable safety profile in relapsing multiple sclerosis (RMS) patients. Objective: The purpose of this study was to report the effects of teriflunomide on ARR and disability progression in pre-specified subgroups. Methods: RMS patients (n=1088) were randomized to placebo or teriflunomide, 7 mg or 14 mg, once daily, for 108 weeks. Subgroup analyses were performed for ARR and disability progression by baseline demographics (gender, race, age), disease characteristics (Expanded Disability Status Scale (EDSS) strata, relapse history, multiple sclerosis (MS) subtype), MRI parameters (gadolinium-enhancing lesions, total lesion volume) and prior use of MS drugs. A generalized estimating equation method and Cox regression model were used to assess consistency of the treatment effect across subgroups, utilizing a treatment-by-subgroup interaction test for each factor separately. Results: Reductions in ARR and disability progression were consistent across subgroups in favor of teriflunomide, with no treatment-by-subgroup interaction test reaching statistical significance. Conclusion: The positive effects of teriflunomide were demonstrated consistently across subgroups in TEMSO.
TL;DR: It is indicated that regular use of aspirin may be associated with reduced risk of breast cancer.
Abstract: Animal and in vitro studies suggest that the use of aspirin may be associated with reduced risk for breast cancer, but results from these studies of the association have been inconsistent The objective of this meta-analysis was to quantitatively summarize the current evidence for such a relationship We searched MEDLINE for studies of aspirin use and breast cancer risk that were published in any language, from January 1, 1966, to July 1, 2011 A total of 33 studies (19 cohort studies, 13 case-control studies, and 1 randomized controlled trial [RCT]) that included 1,916,448 subjects were identified We pooled the relative risks from individual studies using a random-effects model, heterogeneity, and publication bias analyses In a pooled analysis of all studies, aspirin use was associated with reduced risk for breast cancer (odds ratio [OR] = 086, 95% confidence interval [CI] = 081, 092) In the subgroup analysis by study design, results were similar except for RCT (OR = 098, 95% CI = 087, 109) In conclusion, this meta-analysis indicated that regular use of aspirin may be associated with reduced risk of breast cancer More RCT were needed to confirm this association in the future
TL;DR: It is demonstrated that decreasing in Pon1 activity is a risk factor associated with increased CHD susceptibility, and additional very large-scale studies are warranted to provide conclusive evidence on the effects of PON1 activity on risk of CHD.
TL;DR: It is suggested that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures, and the novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.
Abstract: Background Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. Method The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. Results Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. Conclusions Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.
TL;DR: The available evidence does not support routine use of oral LTRAs in acute asthma, and further studies are required to assess whether intravenous treatment can reduce the risk of hospital admission, and what the most appropriate dose regimen is.
Abstract: Background
Acute asthma presentation in the emergency setting frequently leads to hospital admission. Currently available treatment options include corticosteroid therapy, beta2-agonists and oxygen. Antileukotriene agents are beneficial in chronic asthma as additional therapy to inhaled steroids. Their value when used orally or intravenously in the acute setting requires evaluation.
Objectives
To determine if the addition of a leukotriene receptor antagonist (LTRA) produces a beneficial effect in children and adults with acute asthma who are currently receiving inhaled bronchodilators and systemic corticosteroids.
Search methods
We searched the Cochrane Airways Group's Specialised Register of trials with predefined terms. Searches are current to February 2012.
Selection criteria
We included randomised trials comparing antileukotrienes and standard acute asthma care versus placebo and standard care in people with acute asthma of any age. We considered any dose and method of delivery of the leukotriene agent.
Data collection and analysis
Two authors independently assessed studies for inclusion in the review and extracted data. We then checked data and resolved disagreements by discussion. We contacted study authors where necessary to provide additional information and data.
Main results
Eight trials, generating 10 treatment-control comparisons, that recruited 1470 adults and 470 children met the entry criteria. These studies were of mixed quality, and there was heterogeneity in the severity of asthma exacerbation.
For oral treatment, there was no significant difference in hospital admission between LTRAs and control in three trials on 194 children (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.21 to 3.52). Using a broader composite outcome which measured requirement for additional care there was no significant difference between treatments (RR 0.87; 95% CI 0.60 to 1.28). Results demonstrated some indication of improvement in lung function with a significant difference in forced expiratory volume in one second (FEV1) favouring LTRAs in two trials on 641 adults (mean difference (MD) 0.08; 95% CI 0.01 to 0.14). There were insufficient data to assess this outcome in children. The most common adverse event described was headache; however, there was no significant difference between LTRAs and control (RR 0.81; 95% CI 0.22 to 2.99). Due to insufficient numbers, we were unable to conduct a subgroup analysis based on age.
The combined results of two trials of intravenous treatment in 772 adults and one trial in 276 children demonstrated a reduction in the risk of hospital admission which was not quite statistically significant (RR 0.78; 95% CI 0.61 to 1.01). There was a statistically significant small difference in FEV1 in the adult studies (MD 0.12; 95% CI 0.06 to 0.17), but not in the single trial in children (MD 0.01; 95% CI -0.06 to 0.08).
Authors' conclusions
Presently, the available evidence does not support routine use of oral LTRAs in acute asthma. Further studies are required to assess whether intravenous treatment can reduce the risk of hospital admission, and what the most appropriate dose regimen is. Additional research is also needed into safety and efficacy of additional doses for those on maintenance therapy, and larger paediatric trials are required to allow subgroup analysis. Prolonged studies would be required to establish other health economic outcomes in admitted patients.
TL;DR: Decreased PON1 activity associated with CHD risk was observed in almost all subgroup analysis according to ethnicity, sample size, study design, mean age of cases, source, and type of control, and Progressive decrease in serum Pon1 activity may exist for an individual with severe disease.
Abstract: Human paraoxonase 1 (PON1) is a calcium-dependent high-density lipoprotein associated ester hydrolase that has attracted considerable attention as a candidate factor for coronary heart disease (CHD) based on its function as a key factor in lipoprotein catabolism pathways. This meta-analysis aimed to clarify the inconsistency of published studies and to establish a comprehensive picture of the relationship between PON1 activity and CHD susceptibility. A systematic search was performed from PubMed, Web of Science, EMBASE, and CNKI databases. Ratio of means (RoM) between case and control and 95% confidence intervals (CIs) were calculated using a random-effects model. The source of heterogeneity was explored by subgroup analysis and meta-regression. We identified 47 eligible studies including a total of 9853 CHD cases and 11,408 controls. The pooled analysis showed that CHD patients had a 19% lower PON1 activity than did the controls (RoM=0.81; 95% CI: 0.74–0.89, p<10−5). In the subgroup analyses by CHD end p...
TL;DR: It is demonstrated that subclinical hyperthyroidism significantly increased the risk of CVD for the general population and therisk of cardiovascular and all-cause mortality for the individuals with other morbidities.
Abstract: Objectives: Whether subclinical hyperthyroidism (SCH) results in poor prognosis remains controversial. Our aim was to evaluate the association between SCH and the risk of cardiovascular disease (CVD), cardiovascular mortality, and all-cause mortality by conducting a meta-analysis of cohort studies. Methods: The PubMed and Embase databases were searched through November 2011 to identify studies that met pre-stated inclusion criteria. Relevant information for analysis was extracted. Either a fixed or a random effects model was used to calculate the overall combined risk estimates. Results: Seventeen cohort studies were included in this meta-analysis. The overall combined relative risks for individuals with SCH compared with the reference group were 1.19 (95% confidence interval (CI): 1.10 to 1.28) for CVD, 1.52 (95% CI: 1.08 to 2.13) for cardiovascular mortality, and 1.25 (95% CI: 1.00 to 1.55) for all-cause mortality. Subgroup analysis by sample source (community or convenience sample) showed that the significant association for cardiovascular and all-cause mortality only existed when pooling studies from convenience samples. Heterogeneity was observed when pooling studies on the association between SCH and cardiovascular and all-cause mortality. Sensitivity analysis showed omission of each individual study did not significantly change the pooled effects. No evidence of publication bias was observed. Conclusions: Our findings demonstrated that SCH significantly increased the risk of CVD for the general population and the risk of cardiovascular and all-cause mortality for the individuals with other morbidities.
TL;DR: There is still lack of strong evidence of directly comparing the efficacy of amiodarone and beta‐blocker in preventing postoperative AF (POAF).
Abstract: Background
Current guidelines recommend beta-blocker as the first-line preventive treatment of atrial fibrillation (AF) after cardiac surgery; if beta-blocker therapy is contraindicated, then amiodarone is recommended. There is still lack of strong evidence of directly comparing the efficacy of amiodarone and beta-blocker in preventing postoperative AF (POAF).
Aim
This meta-analysis was to determine whether amiodarione and beta-blocker are equally effective and safe, or one is superior in preventing POAF.
Methods
We searched the Medline, Web of Science, Cochrane Library databases and clinical trial databases for related articles published from January 1990 to October 2011. The primary outcome was development of AF after cardiac surgery. We used random-effects model when there was significant heterogeneity between trials and fixed-effects method when heterogeneity was negligible. Moreover, subgroup and sensitivity analyses were also performed.
Results
We identified totally six trials, which involved 1033 patients. The amiodarone group did not significantly differ from the beta-blocker group in AF occurrence (risk ratio 0.77, 95% confidence interval 0.55 to 1.06, P = 0.11) or the length of hospital stay (weighted mean difference −0.05 day, 95% confidence interval −0.64 to 0.54, P = 0.86). Subgroup analysis stratified by different beta-blockers revealed that amiodarone significantly improved POAF as compared with propranolol. In addition, there was no difference in adverse events after operation.
Conclusion
These data indicate that the occurrence of AF and length of hospital stay after surgery are similar in the amiodarone and beta-blocker groups.
TL;DR: New evidence is provided supporting the conclusion that residential exposure to radon can significantly increase the risk of lung cancer in a dose-response manner.
Abstract: Background: Numbers of epidemiological studies assessing residential radon exposure and risk of lung cancer have yielded inconsistent results. Methods: We therefore performed a meta-analysis of relevant published case- control studies searched in the PubMed database through July 2011 to examine the association. The combined odds ratio (OR) were calculated using fixed- or random-effects models. Subgroup and dose-response analyses were also performed. Results: We identified 22 case-control studies of residential radon and lung cancer risk involving 13,380 cases and 21,102 controls. The combined OR of lung cancer for the highest with the lowest exposure was 1.29 (95% CI 1.10-1.51). Dose-response analysis showed that every 100 Bq/m 3 increment in residential radon exposure was associated with a significant 7% increase in lung cancer risk. Subgroup analysis displayed a more pronounced association in the studies conducted in Europe. Studies restricted to female or non-smokers demonstrated weakened associations between exposure and lung cancer. Conclusions: This meta- analysis provides new evidence supporting the conclusion that residential exposure to radon can significantly increase the risk of lung cancer in a dose-response manner.
TL;DR: “Early”
Abstract: Objective: The aim of the study is to summarize the effects of timing of initiation of renal replacement therapy (RRT) on mortality. Methods: A systematic search for randomized controlled trials (RCTs) and other clinical studies was performed without language restriction in PubMed, Web of Science, and Embase. We estimated pooled relative risk ratios (RRs) and 95% confidence intervals (CIs) using fixed effects model or random effects model as appropriate. Heterogeneity, publication bias, and subgroup analyses were conducted. Results: We analyzed the date extracted from 15 studies (3 RCTs, 2 prospective, and 10 retrospective comparative cohort studies) with a total of 2955 patients. Overall, 51.0% (772/1514) patients died in the “early” RRT group compared with 58.0% (836/1441) in the “late” RRT group. The pooled RR was 0.71 (95% CI: 0.59, 0.86), but the heterogeneity existed (p < 0.00001). Subgroup analysis based on modality did not record heterogeneity across trials. In continuous RRT (CRRT) group (n = 607...
TL;DR: The overall data failed to indicate a significant association of H. pylori infection and asthma risk, and in the subgroup analysis regarding ethnicity, source of controls and CagA status, no associations could be observed.
Abstract: Objective: Helicobacter pylori (H. pylori) infection has been thought to play a critical role in disorders such as gastric and lung cancer. A number of studies have been devoted to the relationship between H. pylori infection and asthma risk, which have generated inconclusive results. In this study we aimed to derive a more precise estimation of the relationship.
Methods: Meta-analyses evaluating the association of H. pylori infection and asthma risk were conducted and subgroup analyses on ethnicity and source of controls as well as CagA status were further conducted. Eligible studies were identified for the period up to Jul 2012.
Results: A total of five case-control studies comprising 770 cases and 785 controls were lastly selected for analysis. The overall data failed to indicate a significant association of H. pylori infection and asthma risk (OR=1.01; 95%CI=0.82-1.24). Likewise, in the subgroup analysis regarding ethnicity, source of controls and CagA status, no associations could be observed.
Conclusions: The pooled data failed to suggest a marked association between H. pylori infection and asthma risk. Future studies are needed to confirm this conclusion.
TL;DR: In this study of community-dwelling older men, DBI was not associated with limitations on objective cognitive performance measures or with a clinical diagnosis of mild cognitive impairment or dementia.
Abstract: We aimed to assess the relationship between Drug Burden Index (DBI), a risk assessment tool that measures anticholinergic and sedative medication exposure and cognitive performance, and cognitive impairment in older people. The study population consisted of community-dwelling older men, 70 years or older, living in Sydney, Australia. The Addenbrooke's Cognitive Examination (ACE) and the Trail Making Task (TMT) cognitive tests were performed, and participants were categorized as having intact cognition, mild cognitive impairment, or dementia using clinical diagnostic criteria. The analyses were restricted to participants with English-speaking background (n = 987) and to the subgroup whose cognition was intact (n = 887). In the study group, DBI exposure was not associated with poorer performance on the ACE (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.66-1.47) or the TMT (OR, 0.71; 95% CI, 0.40-1.24) tests, after controlling for covariates. Similarly, DBI exposure was not associated with cognitive impairment (OR, 1.34; 95% CI, 0.83-2.16). There was no association between increasing DBI scores and poorer performance on any of the outcomes. On subgroup analysis of cognitively intact subgroup, DBI exposure or increasing DBI scores were not associated with poorer performance on the ACE or the TMT tests. In this study of community-dwelling older men, DBI was not associated with limitations on objective cognitive performance measures or with a clinical diagnosis of mild cognitive impairment or dementia.
TL;DR: Possible differential effects in surgical and non‐surgical patients were investigated and selective digestive decontamination and selective oropharyngealDecontamination are effective in improving survival in patients under intensive care.
Abstract: BACKGROUND: Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) are effective in improving survival in patients under intensive care. In this study possible differential effects in surgical and non-surgical patients were investigated. METHODS: This was a post hoc subgroup analysis of data from a cluster-randomized multicentre trial comparing three groups (SDD, SOD or standard care) to quantify effects among surgical and non-surgical patients. The primary study outcome was 28-day mortality rate. Duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital length of stay, and bacteraemia rates were secondary outcomes. RESULTS: The subgroup analyses included a total of 2762 surgical and 3165 non-surgical patients. Compared with standard care, adjusted odds ratios (ORs) for mortality were comparable in SDD-treated surgical and non-surgical patients: 0.86 (95 per cent confidence interval 0.69 to 1.09; P = 0.220) and 0.85 (0.70 to 1.03; P = 0.095) respectively. However, duration of mechanical ventilation, ICU stay and hospital stay were significantly reduced in surgical patients who had SDD. SOD did not reduce mortality compared with standard treatment in surgical patients (adjusted OR 0.97, 0.77 to 1.22; P = 0.801); in non-surgical patients it reduced mortality (adjusted OR 0.77, 0.63 to 0.94; P = 0.009) by 16.6 per cent, representing an absolute mortality reduction of 5.5 per cent with number needed to treat of 18. CONCLUSION: Subgroup analysis found similar effects of SDD in reducing mortality in surgical and non-surgical ICU patients, whereas SOD reduced mortality only in non-surgical patients. The hypothesis-generating findings mandate investigation into mechanisms between different ICU populations.
TL;DR: The design and analysis principles presented provide a framework for decision making based on these novel multipopulation tailoring trial designs, considering the particular case of confirmatory trials.
Abstract: This article focuses on statistical analysis of clinical trials pursuing tailored therapy objectives, wherein evaluation of treatment effect occurs in the overall population as well as in a predefined subpopulation(s). The design and analysis principles presented provide a framework for decision making based on these novel multipopulation tailoring trial designs, considering the particular case of confirmatory trials. These principles include traditional multiple testing considerations, as well as 2 new analysis principles.
TL;DR: It is demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations.
Abstract: Objective MicroRNA plays a vital role in gene expression, and microRNA dysregulation is involved in carcinogenesis The miR-196a-2 polymorphism rs11614913 is reportedly associated with cancer susceptibility This meta-analysis was performed to assess the overall association of miR-196a-2 with cancer risk Methods A total of 27 independent case-control studies involving 10,435 cases and 12,075 controls were analyzed for the rs11614913 polymorphism Results A signifi cant association was found between rs11614913 polymorphism and cancer risk in four genetic models (CT vs TT, OR=115, 95%CI=105–127; CC vs TT, OR=123, 95%CI=108–139; Dominant model, OR=117, 95%CI=106–130; Additive model, OR=108, 95%CI=101–114) In the subgroup analysis of different tumor types, the C allele was associated with increased risk of lung, breast, and colorectal cancer, but not with liver, gastric, or esophageal cancer In the subgroup analysis by ethnicity, a significanty increased risk of cancer was found among Asians in all genetic models, but no associations were found in the Caucasian subgroup Conclusions The meta-analysis demonstrated that the miR-196a-2 polymorphism is associated with cancer susceptibility, especially lung cancer, colorectal cancer, and breast cancer among Asian populations
TL;DR: It is logically inconsistent to include biomarker-positive patients in the primary analysis of treatment effect in biomarker -negative patients because of the likelihood that treatment effects would differ between the 2 subgroups.
Abstract: In many settings, testing has been proposed to assess the effect of an experimental regimen within a biomarker-positive subgroup where it is biologically plausible that benefit is stronger in such patients, and in the overall population that also includes biomarker-negative subjects less likely to benefit from that regimen. A statistically favorable result in the biomarker-positive subgroup would lead to a claim for that subgroup, whereas a statistically favorable result for the overall population would lead to a claim that includes both biomarker subgroups. The latter setting is problematic when biomarker-negative patients truly do not benefit from the experimental regimen. When it is prespecified that biomarker-negative patients should not be included in the primary analysis of treatment effect in biomarker-positive patients because of the likelihood that treatment effects would differ between the 2 subgroups, it is logically inconsistent to include biomarker-positive patients in the primary analysis of treatment effect in biomarker-negative patients.
TL;DR: There was a trend for cardioselective beta-blockers to have a greater improvement in mortality when compared with placebo and to have greater impact than non-calcium channel antagonists.
Abstract: Beta-blockers are recommended as first-line symptomatic treatment for stable angina. However, their impact on mortality outside the context of myocardial infarction is unknown. We performed a meta-analysis of all randomized trials of beta-blockers in stable angina. Medical databases and cardiology journals were searched for relevant randomized clinical trials. The primary outcome was cardiovascular mortality, separately considering trials of beta-blockers versus placebo and beta-blockers versus other antianginals. We conducted a subgroup analysis on cardioselective versus non-cardioselective beta-blockers and calcium channel antagonists versus nitrates. We calculated odds ratios (ORs) and confidence intervals (CIs) using Peto's method. We found no statistically significant evidence that beta-blockers impact on mortality when compared with placebo (OR, 0.42; CI, 0.15–1.21) or other antianginals (OR, 0.98; CI, 0.86–1.10), or all others (OR, 0.97; CI, 0.86–1.09). There was a trend for cardioselective beta-bl...
TL;DR: CPT as well as its culturally adapted form and NET seem effective in helping war/conflict traumatised civilians cope with their PTSD symptoms, however, more studies are required if one wishes to recommend one of these therapies above the other.
Abstract: Although war-trauma victims are at a higher risk of developing PTSD, there is no consensus on the effective treatments for this condition among civilians who experienced war/conflict-related trauma. This paper assessed the effectiveness of the various forms of cognitive-behavioral therapy (CBT) at lowering PTSD and depression severity. All published and unpublished randomized controlled trials studying the effectiveness of CBT at reducing PTSD and/or depression severity in the population of interest were searched. Out of 738 trials identified, 33 analysed a form of CBTs effectiveness, and ten were included in the paper. The subgroup analysis shows that cognitive processing therapy (CPT), culturally adapted CPT, and narrative exposure therapy (NET) contribute to the reduction of PTSD and depression severity in the population of interest. The effect size was also significant at a level of 0.01 with the exception of the effect of NET on depression score. The test of subgroup differences was also significant, suggesting CPT is more effective than NET in our population of interest. CPT as well as its culturallyadapted form and NET seem effective in helping war/conflict traumatised civilians cope with their PTSD symptoms. However, more studies are required if one wishes to recommend one of these therapies above the other.