Project description:CONTEXT: Older adults are underrepresented in clinical research. To assess therapeutic efficacy in older patients, some randomized controlled trials (RCTs) include older adults only. OBJECTIVE: To compare treatment effects between RCTs including older adults only (elderly RCTs) and RCTs including all adults (adult RCTs) by a meta-epidemiological approach. METHODS: All systematic reviews published in the Cochrane Library (Issue 4, 2011) were screened. Eligible studies were meta-analyses of binary outcomes of pharmacologic treatment including at least one elderly RCT and at least one adult RCT. For each meta-analysis, we compared summary odds ratios for elderly RCTs and adult RCTs by calculating a ratio of odds ratios (ROR). A summary ROR was estimated across all meta-analyses. RESULTS: We selected 55 meta-analyses including 524 RCTs (17% elderly RCTs). The treatment effects differed beyond that expected by chance for 7 (13%) meta-analyses, showing more favourable treatment effects in elderly RCTs in 5 cases and in adult RCTs in 2 cases. The summary ROR was 0.91 (95% CI, 0.77-1.08, p?=?0.28), with substantial heterogeneity (I(2)?=?51% and ?(2)?=?0.14). Sensitivity and subgroup analyses by type-of-age RCT (elderly RCTs vs RCTs excluding older adults and vs RCTs of mixed-age adults), type of outcome (mortality or other) and type of comparator (placebo or active drug) yielded similar results. CONCLUSIONS: The efficacy of pharmacologic treatments did not significantly differ, on average, between RCTs including older adults only and RCTs of all adults. However, clinically important discrepancies may occur and should be considered when generalizing evidence from all adults to older adults.
Project description:Several studies reported that Tai Chi showed potential effects for chronic pain, but its role remains controversial. This review assessed the evidence regarding the effects of Tai Chi for chronic pain conditions. 18 randomized controlled trials were included in our review. The aggregated results have indicated that Tai Chi showed positive evidence on immediate relief of chronic pain from osteoarthritis (standardized mean difference [SMD], -0.54; 95% confidence intervals [CI], -0.77 to -0.30; P < 0.05). The valid duration of Tai Chi practice for osteoarthritis may be more than 5 weeks. And there were some beneficial evidences regarding the effects of Tai Chi on immediate relief of chronic pain from low back pain (SMD, -0.81; 95% CI, -1.11 to -0.52; P < 0.05) and osteoporosis (SMD, -0.83; 95% CI, -1.37 to -0.28; P = 0.003). Therefore, clinicians may consider Tai Chi as a viable complementary and alternative medicine for chronic pain conditions.
Project description:BACKGROUND:Patients with posttraumatic stress disorder (PTSD) are at increased risk for adverse consequences from comorbid medical conditions. Nonadherence to medications prescribed to treat those comorbid conditions may help explain this increased risk. We sought to determine the association between PTSD and medication nonadherence and whether it varied according to the type of event inducing the PTSD. METHODS:Prospective observational cohort or cross-sectional studies relating PTSD and nonadherence among adults prescribed medications for a chronic medical illness were identified by searching MEDLINE, EMBASE, PsycINFO, the Cochrane Library, CINAHL, SCOPUS, and the PILOTS Database and by hand-searching bibliographies from selected articles. Individual estimates of odds ratios were pooled using random effects meta-analysis with inverse variance weighting. Articles were pooled separately according to whether PTSD was induced by a medical versus non-medical event. OUTCOMES:Sixteen articles comprising 4483 patients met eligibility criteria. The pooled effect size of the risk of PTSD to medication nonadherence was OR 1.22 (95% CI, 1.06-1.41). Among the 6 studies of medical event-induced PTSD, the OR was 2.08 (95% CI, 1.03-4.18); p?=?0.04. Among the 8 studies in which PTSD was not induced by a medical event, the OR was 1.10 (95% CI, 0.99-1.24); p?=?0.09. INTERPRETATION:Patients with PTSD were more likely to be nonadherent to medications prescribed for chronic medical conditions - an association that may exist specifically when PTSD was induced by a medical event. Medications may serve as aversive reminders among survivors of acute medical events, magnifying avoidance behaviors characteristic of PTSD. FUNDING:NHLBI.
Project description:To determine the association of socioeconomic disadvantage with the prevalence of childhood disabling chronic conditions in high-income countries.Systematic review and meta-analyses.6 electronic databases, relevant websites, reference lists and experts in the field.160 observational studies conducted in high-income countries with data on socioeconomic status and disabling chronic conditions in childhood, published between 1 January 1991 and 31 December 2013.Abstracts were reviewed, full papers obtained, and papers identified for inclusion by 2 independent reviewers. Inclusion decisions were checked by a third reviewer. Where reported, ORs were extracted for low versus high socioeconomic status. For studies reporting raw data but not ORs, ORs were calculated. Narrative analysis was undertaken for studies without data suitable for meta-analysis.126 studies had data suitable for meta-analysis. ORs for risk estimates were: all-cause disabling chronic conditions 1.72 (95% CI 1.48 to 2.01); psychological disorders 1.88 (95% CI 1.68 to 2.10); intellectual disability 2.41 (95% CI 2.03 to 2.86); activity-limiting asthma 2.20 (95% CI 1.87 to 2.85); cerebral palsy 1.42 (95% CI 1.26 to 1.61); congenital abnormalities 1.41 (95% CI 1.24 to 1.61); epilepsy 1.38 (95% CI 1.20 to 1.59); sensory impairment 1.70 (95% CI 1.39 to 2.07). Heterogeneity was high across most estimates (I(2)>75%). Of the 34 studies without data suitable for meta-analysis, 26 reported results consistent with increased risk associated with low socioeconomic status.The findings indicate that, in high-income countries, childhood disabling chronic conditions are associated with social disadvantage. Although evidence of an association is consistent across different countries, the review provides limited evidence to explain the association; future research, using longitudinal data, will be required to distinguish low socioeconomic status as the cause or consequence of childhood disabling chronic conditions and the aetiological pathways and mechanisms.
Project description:We established patient-derived organoids and monolayer culture cells from the salivary gland cancer cases. To compare the RNA profiles of primary culture cells (Organoids and monolayer culture cells) and their parental tumors, we isolated total RNA from 2 cases of the salivary gland cancer and performed transcriptome sequencing for the organoids, monolayer culture cells, and their parental tumors of both cases. Case 6 is a case of adenoid cystic carcinoma and Case 11 is a case of salivary duct carcinoma.
Project description:AimsThe neutrophil-lymphocyte ratio (NLR) is a readily available inflammatory biomarker that may associate with atherosclerosis and predict cardiovascular (CV) events. The aims of this study are to determine whether the NLR predicts incident major adverse cardiovascular events (MACE) and is modified by anti-inflammatory therapy.Methods and resultsBaseline and on-treatment NLRs were calculated from complete blood counts among 60 087 participants randomized in the CANTOS, JUPITER, SPIRE-1, SPIRE-2, and CIRT trials to receive placebo or canakinumab, rosuvastatin, bococizumab, or methotrexate, respectively, and followed up for MACE. All analyses were performed first in CANTOS, and then externally validated in the other four trials. For the five trials, hazard ratios for major CV events and mortality comparing NLR quartiles were computed using Cox proportional hazards models, and the effect of each randomized intervention on the NLR was evaluated in comparison to placebo. The NLR modestly correlated with interleukin-6, C-reactive protein, and fibrinogen levels but minimally with lipids. In all five randomized trials, baseline NLR predicted incident CV events and death; the per-quartile increase in risk of MACE was 20% in CANTOS [95% confidence interval (CI) 14-25%, P < 0.0001], 31% in SPIRE-1 (95% CI 14-49%, P = 0.00007), 27% in SPIRE-2 (95% CI 12-43%, P = 0.0002), 9% in CIRT (95% CI 0.2-20%, P = 0.045), and 11% in JUPITER (95% CI 1-22%, P = 0.03). While lipid-lowering agents had no significant impact on the NLR, anti-inflammatory therapy with canakinumab lowered the NLR (P < 0.0001).ConclusionThe NLR, an easily obtained inflammatory biomarker, independently predicts CV risk and all-cause mortality, and is reduced by interleukin-1β blockade with canakinumab.
Project description:Androgen deprivation therapy is a cornerstone of prostate cancer treatment. Pharmacological androgen deprivation includes gonadotropin-releasing hormone agonism and antagonism, androgen receptor inhibition, and CYP17 (cytochrome P450 17A1) inhibition. Studies in the past decade have raised concerns about the potential for androgen deprivation therapy to increase the risk of adverse cardiovascular events such as myocardial infarction, stroke, and cardiovascular mortality, possibly by exacerbating cardiovascular risk factors. In this review, we summarize existing data on the cardiovascular effects of androgen deprivation therapy. Among the therapies, abiraterone stands out for increasing risk of cardiac events in meta-analyses of both randomized controlled trials and observational studies. We find a divergence between observational studies, which show consistent positive associations between androgen deprivation therapy use and cardiovascular disease, and randomized controlled trials, which do not show these associations reproducibly.
Project description:Inflammatory cytokines are commonly elevated in acute depression and are associated with resistance to monoaminergic treatment. To examine the potential role of cytokines in the pathogenesis and treatment of depression, we carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment using clinical trials of chronic inflammatory conditions where depressive symptoms were measured as a secondary outcome. Systematic search of the PubMed, EMBASE, PsycINFO and Cochrane databases, search of reference lists and conference abstracts, followed by study selection process yielded 20 clinical trials. Random effect meta-analysis of seven randomised controlled trials (RCTs) involving 2370 participants showed a significant antidepressant effect of anti-cytokine treatment compared with placebo (standardised mean difference (SMD)=0.40, 95% confidence interval (CI), 0.22-0.59). Anti-tumour necrosis factor drugs were most commonly studied (five RCTs); SMD=0.33 (95% CI; 0.06-0.60). Separate meta-analyses of two RCTs of adjunctive treatment with anti-cytokine therapy and eight non-randomised and/or non-placebo studies yielded similar small-to-medium effect estimates favouring anti-cytokine therapy; SMD=0.19 (95% CI, 0.00-0.37) and 0.51 (95% CI, 0.34-0.67), respectively. Adalimumab, etanercept, infliximab and tocilizumab all showed statistically significant improvements in depressive symptoms. Meta-regression exploring predictors of response found that the antidepressant effect was associated with baseline symptom severity (P=0.018) but not with improvement in primary physical illness, sex, age or study duration. The findings indicate a potentially causal role for cytokines in depression and that cytokine modulators may be novel drugs for depression in chronically inflamed subjects. The field now requires RCTs of cytokine modulators using depression as the primary outcome in subjects with high inflammation who are free of other physical illnesses.
Project description:ObjectiveTo determine the degree to which chronic conditions might contribute to the unexplained burden of herpes zoster.MethodsWe conducted a case-control study using MarketScan data from January 1, 2007, through December 31, 2007, to investigate chronic conditions as risk factors for herpes zoster among persons 20 to 64 years old. Cases were enrollees with a herpes zoster diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification codes 053.xx), and controls were those without a herpes zoster diagnosis, matched by age groups and insurance plan. We selected 10 chronic conditions based on their prevalence in the general population. We calculated the attributable fraction and created a comorbidity composite score by summing the significant coefficient of regression of chronic conditions. We used logistic regression to evaluate the associations between herpes zoster and chronic conditions.ResultsWe identified a total of 59,173 cases and 616,177 controls for the analysis. Risk of herpes zoster was significant for 8 of the 10 study conditions (odds ratios, 1.06-1.52). Herpes zoster risk also increased as a function of comorbidity composite score. The attributable fractions for these 8 significant conditions ranged from 0.24% to 2.89%.ConclusionThe risk of herpes zoster may be increased in people with chronic conditions. However, this risk may not contribute substantially to the burden of herpes zoster in the population. The causes for most cases of herpes zoster remain unknown.
Project description:BACKGROUND: Individual patient data meta-analyses (IPDMAs) prevail as the gold standard in clinical evaluations. We investigated the distribution and epidemiological characteristics of published IPDMA articles. METHODOLOGY/PRINCIPAL FINDINGS: IPDMA articles were identified through comprehensive literature searches from PubMed, Embase, and Cochrane library. Two investigators independently conducted article identification, data classification and extraction. Data related to the article characteristics were collected and analyzed descriptively. A total of 829 IPDMA articles indexed until 9 August 2012 were identified. An average of 3.7 IPDMA articles was published per year. Malignant neoplasms (267 [32.2%]) and circulatory diseases (179 [21.6%]) were the most frequently occurring topics. On average, each IPDMA article included a median of 8 studies (Interquartile range, IQR 5 to 15) involving 2,563 patients (IQR 927 to 8,349). Among 829 IPDMA articles, 229 (27.6%) did not perform a systematic search to identify related studies. In total, 207 (25.0%) sought and included individual patient data (IPD) from the "grey literature". Only 496 (59.8%) successfully obtained IPD from all identified studies. CONCLUSIONS/SIGNIFICANCE: The number of IPDMA articles exhibited an increasing trend over the past few years and mainly focused on cancer and circulatory diseases. Our data indicated that literature searches, including grey literature and data availability were inconsistent among different IPDMA articles. Possible biases may arise. Thus, decision makers should not uncritically accept all IPDMAs.