Topiramate for acute affective episodes in bipolar disorder in adults

Bipolar disorder is a common recurrent illness with high levels of chronicity. Previous trials have suggested that the anticonvulsant topiramate may be efficacious in bipolar disorder. This is an update of a previous Cochrane review (last published 2006) on the role of topiramate in bipolar disorder.To assess the effects of topiramate for acute mood episodes in bipolar disorder in adults compared to placebo, alternative pharmacological treatment, and combination pharmacological treatment as measured by treatment of symptoms on specific rating scales for individual episodes.We searched the Cochrane Depression, Anxiety and Neurosis Controlled Trials Register to 13 October 2015, which includes records from the Cochrane Central Register of Controlled Trials (CENTRAL) all years; MEDLINE 1950-; EMBASE 1974-; and PsycINFO 1967-.We performed handsearching, reviewing of grey literature and reference lists, and correspondence with authors and pharmaceutical companies.Randomised controlled trials comparing topiramate with placebo or with active agents in the treatment of acute mood episodes in adult male and female patients with bipolar disorder.Two review authors independently performed data extraction and methodological quality assessment. For analysis, we used odds ratio (OR) for binary efficacy outcomes and mean difference (MD) for continuously distributed outcomes.This review included six studies with a total of 1638 male and female participants, of all ethnic backgrounds in both inpatient and outpatient settings. In five studies, participants were experiencing a manic or mixed episode, and in the other study the participants met the criteria for a depressive phase. Topiramate was compared with placebo and alternative pharmacological treatment as both monotherapy and as adjunctive treatment.Moderate-quality evidence showed topiramate to be no more or less efficacious than placebo as monotherapy, in terms of mean change on Young Mania Rating Scale (YMRS) (range 0 to 60), at endpoint 3 weeks (MD 1.17, 95% confidence interval (CI) -0.52 to 2.86; participants = 664; studies = 3; P = 0.17) and at endpoint 12 weeks (MD -0.58, 95% CI -3.45 to 2.29; participants = 212; studies = 1; P = 0.69; low-quality evidence). For the same outcome, low-quality evidence also showed topiramate to be no more or less efficacious than placebo as add-on therapy (endpoint 12 weeks) (MD -0.14, 95% CI -2.10 to 1.82; participants = 287; studies = 1; P = 0.89) in the treatment of manic and mixed episodes. We found high-quality evidence that lithium was more efficacious than topiramate as monotherapy in the treatment of manic and mixed episodes in terms of mean change on YMRS (range 0 to 60) (endpoint 12 weeks) (MD 8.46, 95% CI 5.86 to 11.06; participants = 449; studies = 2; P < 0.00001).For troublesome side effects experienced of any nature, we found no difference between topiramate and placebo as monotherapy (endpoint 12 weeks) (OR 0.68, 95% CI 0.33 to 1.40; participants = 212; studies = 1; P = 0.30; low-quality evidence) or as add-on therapy (endpoint 12 weeks) (OR 1.10, 95% CI 0.58 to 2.10; participants = 287; studies = 1; P = 0.76; low-quality evidence). In terms of participants experiencing side effects of any nature, we found no difference between topiramate and an alternative drug as monotherapy (endpoint 12 weeks) (OR 0.87, 95% CI 0.50 to 1.52; participants = 230; studies = 1; P = 0.63; low-quality evidence) or as add-on therapy (endpoint 8 weeks) (OR 1.57, 95% CI 0.42 to 5.90; participants = 36; studies = 1; P = 0.50; very low-quality evidence).We considered five of the studies to be at low risk of selection bias for random sequence generation, performance, detection, attrition, and reporting biases, and at unclear risk for allocation concealment and other potential sources of bias. We considered the McIntyre 2000 study to be at high risk of performance bias; unclear risk of bias for random sequence generation, allocation concealment, blinding of outcome assessment, and other potential sources of bias; and at low risk for attrition bias and reporting bias.It is not possible to draw any firm conclusions about the use of topiramate in clinical practice from this evidence. The only high-quality evidence found was that lithium is more efficacious than topiramate when used as monotherapy in the treatment of acute affective episodes in bipolar disorder, and we note that this evidence came from only two studies. Moderate-quality evidence showed that topiramate was no more or less efficacious than placebo as monotherapy when a 3-week endpoint was used, but the quality of the evidence for this outcome at a 12-week endpoint dropped to low. As we graded the quality of the evidence for the other findings as low and very low, it was not possible to draw any conclusions from the results.To best address this research question, if investigators see the indication in so doing, more double-blind randomised controlled trials could be conducted that are more explicit with regard to methodological issues. In particular, investigators could compare placebo, alternative, and combination treatments (including a wide range of mood stabilisers), atypical antipsychotics for manic and mixed episodes, and antidepressants in combination with mood stabilisers or atypical antipsychotics for depressive episodes

The gender and geography of publishing: a review of sex/gender reporting and author representation in leading general medical and global health journals

Introduction Diverse gender and geographical representation matters in research. We aimed to review medical and global health journals’ sex/gender reporting, and the gender and geography of authorship.Methods 542 research and non-research articles from 14 selected journals were reviewed using a retrospective survey design. Paper screening and systematic data extraction was conducted with descriptive statistics and regression analyses calculated from the coded data. Outcome measures were journal characteristics, the extent to which published articles met sex/gender reporting guidelines, plus author gender and location of their affiliated institution.Results Five of the fourteen journals explicitly encourage sex/gender analysis in their author instructions, but this did not lead to increased sex/gender reporting beyond the gender of study participants (OR=3.69; p=0.000 (CI 1.79 to 7.60)). Just over half of research articles presented some level of sex/gender analysis, while 40% mentioned sex/gender in their discussion. Articles with women first and last authors were 2.4 times more likely to discuss sex/gender than articles with men in those positions (p=0.035 (CI 1.062 to 5.348)). First and last authors from high-income countries (HICs) were 19 times as prevalent as authors from low-income countries; and women from low-income and middle-income countries were at a disadvantage in terms of the impact factor of the journals they published in.Conclusion Global health and medical research fails to consistently apply a sex/gender lens and remains largely the preserve of authors in HIC. Collaborative partnerships and funding support are needed to promote gender-sensitive research and dismantle historical power dynamics in authorship

Physical vs. multidimensional frailty in older adults with and without heart failure

Aims The assessment of frailty in older adults with heart failure (HF) is still debated. Here, we compare the predictive role and the diagnostic accuracy of physical vs. multidimensional frailty assessment on mortality, disability, and hospitalization in older adults with and without HF. Methods and results A total of 1077 elderly (≥65 years) outpatients were evaluated with the physical (phy‐Fi) and multidimensional (m‐Fi) frailty scores and according to the presence or the absence of HF. Mortality, disability, and hospitalizations were assessed at baseline and after a 24 month follow‐up. Cox regression analysis demonstrated that, compared with phy‐Fi score, m‐Fi score was more predictive of mortality [hazard ratio (HR) = 1.05 vs. 0.66], disability (HR = 1.02 vs. 0.89), and hospitalization (HR = 1.03 vs. 0.96) in the absence and even more in the presence of HF (HR = 1.11 vs. 0.63, 1.06 vs. 0.98, and 1.14 vs. 1.03, respectively). The area under the curve indicated a better diagnostic accuracy with m‐Fi score than with phy‐Fi score for mortality, disability, and hospitalizations, both in absence (0.782 vs. 0.649, 0.763 vs. 0.695, and 0.732 vs. 0.666, respectively) and in presence of HF (0.824 vs. 0.625, 0.886 vs. 0.793, and 0.812 vs. 0.688, respectively). Conclusions The m‐Fi score is able to predict mortality, disability, and hospitalizations better than the phy‐Fi score, not only in absence but also in presence of HF. Our data also demonstrate that the m‐Fi score has better diagnostic accuracy than the phy‐Fi score. Thus, the use of the m‐FI score should be considered for the assessment of frailty in older HF adults

Chronic obstructive pulmonary disease and long-term mortality in elderly subjects with chronic heart failure

Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are associated with high rates of mortality in elderly subjects. Concurrent CHF and COPD frequently occur, especially in with advancing age. This study examines long-term mortality in community-dwelling elderly subjects affected by CHF alone, COPD alone, and coexistent CHF and COPD. The study evaluated 12-years mortality in 1288 subjects stratified for the presence or absence of CHF or COPD alone, and for coexistence of CHF and COPD. Mortality, at 12 year follow-up, was 46.7% overall, 68.6% in the presence of CHF alone (p < 0.001), 56.9% in the presence of COPD alone (p < 0.01); mortality was 86.2% where CHF and COPD coexisted (p < 0.001) and was significantly higher than in CHF or COPD alone (p < 0.05). Multivariate analysis indicates that CHF (Hazard risk = 1.67, 95% confidence interval 1.15-3.27, p < 0.031) and COPD (Hazard risk = 1.27, 95% confidence interval = 1.08-1.85, p < 0.042) were predictive of long-term mortality. When CHF and COPD simultaneously occurred, the risk dramatically increased up to 3.73 (95% confidence interval = 1.19-6.93, p < 0.001). Long-term follow-up showed higher mortality among elderly subjects affected by CHF or COPD. Simultaneous presence of CHF and COPD significantly increased the risk of death. Therefore, the presence of COPD in CHF patients should be considered a relevant factor in predicting high risk of mortality