Recently Published Projects

Objectives: Objective. To assess efficacy of intermittent inhaled corticosteroid (ICS) therapy in different populations (0 to 4 years old with recurrent wheezing, 5 years and older with persistent asthma, with or without long-acting beta agonist [LABA]), and to assess efficacy of added long-acting muscarinic antagonist (LAMA) in patients 12 years and older with uncontrolled, persistent asthma. Data sources. MEDLINE®, Embase®, Cochrane Central, and Cochrane Database of Systematic Reviews bibliographic databases from earliest date through March 23, 2017; hand searches of references of relevant studies; www.clinicaltrials.gov and the International Controlled Trials Registry Platform. Review methods. Two investigators screened abstracts of identified references for eligibility and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence for each comparison and outcome. Outcomes for which data were extracted included exacerbations, mortality, asthma control composite scores, spirometry, asthma-specific quality of life, and rescue medication use. Results. We included 56 unique studies (54 randomized controlled trials, 2 observational studies) in this review. Compared to rescue short-acting beta-agonist (SABA) use, adding intermittent ICS reduces the risk of exacerbation requiring oral steroids and improves caregiver quality of life in children less than 5 years old with recurrent wheezing in the setting of a respiratory tract infection (RTI). In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence, leading to primarily low strength of evidence ratings. Using ICS and LABA as both a controller and quick relief therapy reduced the risk of exacerbations and improved symptom control in patients 12 years and older compared to ICS controller (with or without LABA). Data in patients 4 to 11 years old suggest lower risk of exacerbations with ICS and LABA controller and quick relief use, but with a lower strength of evidence than in the older population. In patients 12 years and older with uncontrolled, persistent asthma, LAMA versus placebo as add-on to ICS reduces the risk of exacerbations requiring systemic corticosteroids and improves lung function measure through spirometry. Current evidence does not suggest that a difference exists in the efficacy of LAMA versus LABA as add-on to ICS. Triple therapy of ICS, LAMA, and LABA improves lung function measured through spirometry, although the risk of exacerbation was not different versus ICS and LABA. Conclusions. Intermittent ICS added to SABA during an RTI provides benefit to patients less than 5 years of age with recurrent wheezing. In patients 12 years and older with persistent asthma, differences in intermittent ICS versus controller use of ICS were not detected, although few studies provided evidence for this question. In patients 12 years and older with persistent asthma, using ICS and LABA as both a controller and quick relief therapy may be more effective at preventing exacerbations than ICS controller (with or without LABA). LAMA is effective in the management of uncontrolled, persistent asthma in patients 12 years of age and older, and current evidence does not suggest a difference between LAMA and LABA as add-on to ICS.

Objectives: Objective. To assess select adverse events of antidepressants in the treatment of major depressive disorder (MDD) in adults 65 years old or older. Antidepressants included in this review, as determined by expert opinion, are selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), bupropion, mirtazapine, trazodone, vilazodone and vortioxetine. Data sources. MEDLINE®, Embase®, Cochrane Central, and PsycINFO bibliographic databases from earliest date through May 15, 2018; hand searches of references of relevant studies; www.clinicaltrials.gov and the International Controlled Trials Registry Platform. Review methods. Two investigators screened abstracts and subsequently reviewed full-text files. We abstracted data, performed meta-analyses when appropriate, assessed the risk of bias of each individual study, and graded the strength of evidence (SOE) for each comparison and select outcomes. Number needed to harm (NNH) is reported for graded outcomes with statistically significant findings. Results. Nineteen RCTs and two observational studies reported in 41 articles were included. Studies mostly evaluated treatment of the acute phase (<12 weeks) of MDD which was of moderate severity in patients 65 years and older, required subjects to be free from uncontrolled medical comorbidities or psychological conditions, and relied on spontaneous reporting of adverse events. Evidence was scarce and conclusions (based on statistical significance) for a given comparison and outcome are based often on a single study; particularly for specific adverse events. None of the RCTs were powered or designed to capture adverse events and most RCTs studied low doses of antidepressants. Observational data were limited by residual confounding. SSRIs (escitalopram and fluoxetine, moderate SOE), vortioxetine (high SOE) and bupropion XR (moderate SOE) led to a statistically similar frequency of adverse events compared with placebo; whereas SNRIs (duloxetine and venlafaxine) were found to cause a greater number of adverse events (high SOE, NNH 10) compared with placebo during treatment of the acute phase of MDD. Both SSRIs (citalopram, escitalopram and fluoxetine) and SNRIs caused a greater number of withdrawals due to adverse events compared with placebo (SSRIs low SOE, NNH 11; SNRIs moderate SOE, NNH 17). Duloxetine led to a greater number of falls compared with placebo (moderate SOE, NNH 10) during 24 weeks treatment. A single observational study provided evidence on long term use of antidepressants (low SOE) and suggested increased risk of adverse events (SSRIs), falls (SSRIs, SNRI venlafaxine, mirtazapine, trazadone), fractures (SSRIs, SNRI venlafaxine, mirtazapine), and mortality (SSRIs, SNRI venlafaxine, mirtazapine, trazadone), compared to no antidepressant. Evidence for the comparative harms of different antidepressants was limited to single RCTs mostly studying treatment of the acute phase of MDD (<12 weeks). Comparing SSRIs to each other or SSRIs to SNRIs showed statistically similar rates of adverse events (moderate SOE). SSRIs (paroxetine, citalopram, sertraline) had fewer withdrawals due to adverse events compared with TCAs (amitriptyline or nortriptyline) (low SOE, NNT 13) as did mirtazapine compared with paroxetine (low SOE, NNT 9). Vortioxetine had fewer adverse events compared with duloxetine (high SOE, NNT 6 ). Increasing age was associated with greater incidence of serious adverse events with escitalopram (low SOE). The increased risk of falls on duloxetine may be associated with the presence of cardiopulmonary conditions (low SOE). Conclusions. In patients 65 years of age or older with MDD, treatment of the acute phase of MDD with SNRIs (duloxetine and venlafaxine) led to a greater number of adverse events compared with placebo while adverse events were statistically similar to placebo with SSRIs (escitalopram, fluoxetine), vortioxetine and bupropion. SSRIs (citalopram, escitalopram and fluoxetine) and SNRIs (duloxetine and venlafaxine) led to a greater number of study withdrawals due to adverse events compared with placebo and duloxetine increased the risk of falls. Further characterization of the comparative safety of antidepressants is difficult because few studies were identified, comparisons were based on statistical significance, trials were not powered to identify small difference in adverse events and observational studies may be confounded. Comparative, long-term, well-designed studies that report specific adverse events are needed to better inform decisionmaking in this population.

Objectives: Technical brief

Objectives: The objectives of this database are to: 1. Systematically compile and provide access to primary, English-language, peer-reviewed science linking dietary fiber intake in humans to one or more of 10 potential health benefits 2. Provide researchers with a tool to understand how different fibers are characterized in studies 3. Facilitate researchers in identifying gaps in the current research 4. Create a database to serve as a starting foundation of primary human literature for conducting evidence-based reviews and meta-analyses 5. Efficiently assist researchers in identifying fibers of interest. This database should serve as a foundation for future work. Specific inclusion and exclusion criteria, detailed in the user manual, were applied in determining database eligibility; thus, this database is not intended to serve as a sole source for identifying all possible fiber literature for the purposes of conducting a meta-analysis or systematic review. This database contains Population, Intervention, Comparator, and Outcome (PICO) data to help users formulate and narrow the focus of their research question. It is expected that secondary searches will be conducted to augment this database.

Objectives: Background. Posttraumatic stress disorder (PTSD) reduces quality of life and functioning. People with PTSD have symptoms such as intrusive thoughts, nightmares, flashbacks, avoidance of trauma-related stimuli, negative beliefs about oneself and/or others, and hypervigilance. The symptoms may be due to direct or indirect exposure to trauma, such as witnessing actual or threatened death, injury, or violence including sexual violence and threats of harm. Although recent clinical practice guidelines and reviews exist, providing a single, updatable source of PTSD treatment trials would be useful for clinicians, researchers, and policymakers. Purpose. To provide detailed information on PTSD treatment research, we systematically abstracted data from randomized controlled trials (RCTs) of PTSD interventions. The National Center for Posttraumatic Stress Disorder (NCPTSD) intends to use the data to develop a publicly available data repository. The NCPTSD is part of the U.S. Department of Veterans Affairs. Data Sources. We searched PTSDpubs (formerly PILOTS), Ovid® MEDLINE®, Cochrane CENTRAL, PsycINFO®, Embase®, CINAHL®, and Scopus® for eligible RCTs and reviewed reference lists of selected systematic reviews and clinical practice guidelines. Methods. In consultation with NCPTSD, we established inclusion criteria for RCTs and specific data elements to be abstracted. We dually reviewed citations from the literature search, and then the full text of potentially includable articles for eligibility, resolving any disagreements using consensus. One team member abstracted data from included RCTs into evidence tables, and a second reviewer checked abstracted data for accuracy and completeness. The primary publication for each RCT was abstracted; data and citations from any secondary publications (i.e., companion papers) appear in the same record. Findings. We identified 318 RCTs of PTSD interventions for abstraction (106 pharmacologic studies and 212 nonpharmacologic studies) published from 1988 to 2018, with a peak number of publications (31) in 2015. Psychotherapeutic interventions were the most commonly studied (55%), whereas 30 percent evaluated pharmacologic interventions. Most studies were conducted in the United States (61%), and most had sample sizes in the range of 25 to 100 participants (60% of studies) with a relatively small number of studies enrolling fewer than 25 participants (18%). More studies enrolled participants from a community population (57%) than from a military, veteran or other population, and the majority of studies were conducted in the outpatient setting (67%). Studies most often enrolled participants with a mix of trauma types (51%), followed by studies of participants with combat-related trauma (20%). Although there was wide variation, the most commonly used PTSD assessment methods were the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM (SCID). Less than half of the studies reported loss of PTSD diagnosis or clinically meaningful response/remission of symptoms. Several other data elements were infrequently reported, including the number of participants with a history of traumatic brain injuries and the number of trauma types. Conclusions. The data abstracted from 318 RCTs of treatments for PTSD can be used to create a publicly available data repository. By identifying important gaps in the research, such a data repository can inform future study design and conduct.