Irma Klerings

Efficacy and safety of levomilnacipran, vilazodone and vortioxetine compared with other second-generation antidepressants for major depressive disorder in adults: A systematic review and network meta-analysis

BACKGROUND Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants. METHODS We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses. RESULTS Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low. LIMITATIONS Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses. CONCLUSIONS Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.

Continuing education for the prevention of mild cognitive impairment and Alzheimer's-type dementia: A systematic review protocol

BackgroundBecause of the enormous social and economic burden of disease, the prevention of mild cognitive impairment and Alzheimer’s-type dementia has become a major global public health priority. Studies show that cognitively stimulating activities during middle adulthood might have a protective effect on the brain by boosting the cognitive reserve. The aim of this review is to identify evidence investigating the effects of continuing education for the prevention of mild cognitive impairment and Alzheimer’s-type dementia in late life.MethodsOur approach employs a two-stage design: First, we will conduct a systematic review to assess the preventive effects of continuing education on mild cognitive impairment and Alzheimer’s-type dementia. Second, because we expect to find few studies, we will perform a review of systematic reviews on leisure activities that mimic formal continuing education to determine their effects on the prevention of mild cognitive impairment and Alzheimer’s-type dementia. We will search electronic databases (e.g., MEDLINE, PsycINFO, EMBASE, CENTRAL, CINAHL, and Scopus) for published studies and gray literature databases (e.g., trial registries) for unpublished studies.Two authors will independently screen abstracts and full-texts using pre-defined eligibility criteria, select studies, extract data, and assess the quality of included studies or reviews. Outcomes of interest include the incidence of mild cognitive impairment or Alzheimer’s-type dementia, quality of life, functional capacity, and psychological wellbeing. Intermediate outcomes are cognitive (test) performance, cognitive functioning, and social inclusion. The review team is a multidisciplinary group consisting of methodological experts and dementia, geriatrics, and continuing education researchers.DiscussionWe anticipate that our review will highlight serious gaps in the current evidence. Results will build the basis for further research regarding the relation of continuing education and cognitive decline and dementia.Systematic review registrationPROSPERO CRD42017063944

Impact of timing of surgery in elderly hip fracture patients: a systematic review and meta-analysis

We aimed to assess the impact of timing of surgery in elderly patients with acute hip fracture on morbidity and mortality. We systematically searched MEDLINE, the Cochrane Library, Embase, PubMed, and trial registries from 01/1997 to 05/2017, as well as reference lists of relevant reviews, archives of orthopaedic conferences, and contacted experts. Eligible studies had to be randomised controlled trials (RCTs) or prospective cohort studies, including patients 60 years or older with acute hip fracture. Two authors independently assessed study eligibility, abstracted data, and critically appraised study quality. We conducted meta-analyses using the generic inverse variance model. We included 28 prospective observational studies reporting data of 31,242 patients. Patients operated on within 48 hours had a 20% lower risk of dying within 12 months (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.66–0.97). No statistical significant different mortality risk was observed when comparing patients operated on within or after 24 hours (RR 0.82, 95% CI 0.67–1.01). Adjusted data demonstrated fewer complications (8% vs. 17%) in patients who had early surgery, and increasing risk for pressure ulcers with increased time of delay in another study. Early hip surgery within 48 hours was associated with lower mortality risk and fewer perioperative complications.

Effects of lifestyle changes on adults with prediabetes: A systematic review and meta-analysis

AIMS To assess the efficacy, safety, and cost-effectiveness of lifestyle intervention, compared with treatment as usual in people with prediabetes as defined by the American Diabetes Association. For older studies, we used the 1985 World Health Organization definition. METHODS We systematically searched multiple electronic databases and referenced lists of pertinent review articles from January 1980 through November 2015. We performed an update search in MEDLINE on April 26, 2017. Based on a priori established eligibility criteria, we dually reviewed the literature, extracted data, and rated the risk of bias of included studies with validated checklists. To assess the efficacy of lifestyle intervention to prevent or delay further progression to type 2 diabetes, we conducted a random-effects meta-analysis. We assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULT Pooled results of 16 randomized controlled trials showed that people with prediabetes who received lifestyle intervention had a lower rate of progression to type 2 diabetes after one (4% vs. 10%, RR 0.46 [CI 0.32, 0.66]) and three years of follow-up (14% vs. 23%, RR 0.64 [95% CI 0.53, 0.77]). The majority of the studies also showed a greater weight loss in lifestyle intervention participants, with a great variation between studies. Costs per quality-adjusted life-year were lower when the benefits of lifestyle intervention were analyzed over a lifelong time horizon compared to only the period of lifestyle intervention (three years) or to modeling over a ten-year period. CONCLUSION Lifestyle intervention is an efficacious, safe, and cost-effective measure to reduce the risk of progression to type 2 diabetes in people diagnosed with prediabetes. More research is necessary to compare the efficacy of various modes, frequencies, and intensities of lifestyle intervention across studies.