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Treatment-resistant major depression is common and potentially life-threatening in elderly people, in whom little is known about the benefits and risks of augmentation pharmacotherapy. We aimed to assess whether aripiprazole is associated with a higher probability of remission than is placebo. We did a randomised, double-blind, placebo-controlled trial at three centres in the USA and Canada to test the efficacy and safety of aripiprazole augmentation for adults aged older than 60 years with treatment-resistant depression (Montgomery Asberg Depression Rating Scale [MADRS] score of ≥15). Patients who did not achieve remission during a pre-trial with venlafaxine extended-release (150–300 mg/day) were randomly assigned (1:1) to the addition of aripiprazole (target dose 10 mg [maximum 15 mg] daily) daily or placebo for 12 weeks. The computer-generated randomisation was done in blocks and stratified by site. Only the database administrator and research pharmacists had knowledge of treatment assignment. The primary endpoint was remission, defined as an MADRS score of 10 or less (and at least 2 points below the score at the start of the randomised phase) at both of the final two consecutive visits, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00892047. From July 20, 2009, to Dec 30, 2013, we recruited 468 eligible participants, 181 (39%) of whom did not remit and were randomly assigned to aripiprazole (n=91) or placebo (n=90). A greater proportion of participants in the aripiprazole group achieved remission than did those in the placebo group (40 [44%] vs 26 [29%] participants; odds ratio [OR] 2·0 [95% CI 1·1–3·7], p=0·03; number needed to treat [NNT] 6·6 [95% CI 3·5–81·8]). Akathisia was the most common adverse effect of aripiprazole (reported in 24 [26%] of 91 participants on aripiprazole vs 11 [12%] of 90 on placebo). Compared with placebo, aripiprazole was also associated with more Parkinsonism (15 [17%] of 86 vs two [2%] of 81 participants), but not with treatment-emergent suicidal ideation (13 [21%] of 61 vs 19 [29%] of 65 participants) or other measured safety variables. In adults aged 60 years or older who do not achieve remission from depression with a first-line antidepressant, the addition of aripiprazole is effective in achieving and sustaining remission. Tolerability concerns include the potential for akathisia and Parkinsonism. National Institute of Mental Health, UPMC Endowment in Geriatric Psychiatry, Taylor Family Institute for Innovative Psychiatric Research, National Center for Advancing Translational Sciences, and the Campbell Family Mental Health Research Institute.

In this randomized, controlled trial, supplementation of docosahexaenoic acid in preterm infants born before 29 weeks of gestation did not result in a lower risk of bronchopulmonary dysplasia than a control emulsion and may have resulted in a greater risk. Bronchopulmonary dysplasia is a serious complication of preterm birth. It is characterized by an inflammatory process causing abnormal lung development, decreased vascular and alveolar development, 1 and the need for supplemental oxygen or assisted ventilation at 36 weeks of postmenstrual age (gestational age [weeks between the first day of the last menstrual period and birth] plus chronological age [weeks elapsed after birth]). 2 Bronchopulmonary dysplasia is associated with long-term pulmonary and neurodevelopmental impairment and increased needs for health and education services. 3 , 4 Some evidence has suggested that the n−3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA) may help protect against the development . . .

In this randomized, controlled trial of elderly patients with major depression who had had a response to initial treatment with paroxetine and psychotherapy, two years of maintenance paroxetine prevented recurrent depression, but maintenance psychotherapy did not. Major depression recurred in 35 percent of patients receiving paroxetine plus psychotherapy, 37 percent of those receiving paroxetine plus clinical-management sessions, 68 percent of those receiving placebo plus psychotherapy, and 58 percent of those receiving placebo plus clinical-management sessions. In elderly patients with major depression who had had a response to initial treatment with paroxetine and psychotherapy, two years of maintenance paroxetine prevented recurrent depression, but maintenance psychotherapy did not. Depression has a strong tendency to recur in elderly persons, with rates of recurrence of 50 to 90 percent over a period of two to three years 1 ; hence, the goal of treatment is not only recovery but also the prevention of recurrence. 2 Finding practical and affordable depression-management strategies that prevent recurrence is of great importance. 3 – 6 There are few data from controlled studies on the efficacy of maintenance antidepressant medication or depression-specific psychotherapy in patients 70 years of age or older. We have reported that maintenance nortriptyline, monthly interpersonal psychotherapy, and the two in combination 7 are superior to placebo . . .

BackgroundVery preterm children are at increased risk of language delays. Concerns have been raised about the utility of standardised English language tools to diagnose language delay in linguistically diverse children. Our study investigated the incidence of language delay at 4 years in linguistically diverse very preterm children.MethodsVery preterm children born in South Western Sydney, Australia, between 2012 and 2016, were assessed with the Clinical Evaluation of Language Fundamentals Preschool-2 (CELF-P2) tool at 4 years of age. We sought to determine the incidence of language delay in this cohort using language scores from the CELF-P2 assessment tool, and explore potential predictors associated with language delay.ResultsOne hundred and sixty very preterm children attended the 4-year assessment out of the included 270 long-term survivors. At 4 years, 76 (52%) very preterm children had language delay diagnosed using the CELF-P2 assessment tool. Children who preferred a language other than English had lower average core language scores on the CELF-P2 assessment tool (75.1±14.4) compared with children that preferred English (86.5±17.9); p=0.002. Very preterm children growing up in households that preferenced a language other than English and those who were born from multiple births had higher odds of language delay at 4 years (AOR 10.30 (95% CI 2.82 to 38.28); p<0.001 and AOR 2.93 (95% CI 1.20 to 7.14); p=0.018, respectively). Assessing these children using an English language tool may have affected language scores at 4 years.ConclusionsIn this metropolitan setting, very preterm children from linguistically diverse backgrounds were found to be vulnerable to language delays at 4 years. Further large-scale studies evaluating the language outcomes of linguistically diverse preterm children with more culturally appropriate tools are warranted. We question the utility of standardised English language tools to assess language outcomes of linguistically diverse populations.

Comorbid anxiety is common in depressive disorders in both middle and late life, and it affects response to antidepressant treatment. To examine whether anxiety symptoms predict acute and maintenance (2 years) treatment response in late-life depression. Data were drawn from a randomised double-blind study of pharmacotherapy and interpersonal psychotherapy for patients age 70 years and over with major depression. Anxiety symptoms were measured using the Brief Symptom Inventory. Survival analysis tested the effect of pre-treatment anxiety on response and recurrence. Patients with greater pretreatment anxiety took longer to respond to treatment and had higher rates of recurrence. Actuarial recurrence rates were 29% (pharmacotherapy, lower anxiety), 58% (pharmacotherapy, higher anxiety), 54% (placebo, lower anxiety) and 81% (placebo, higher anxiety). Improved identification and management of anxiety in late-life depression are needed to achieve response and stabilise recovery.

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

The authors detail the public health need for depression prevention research and the decisions made in designing an experiment testing problem solving therapy as “indicated” preventive intervention for high-risk older adults with subsyndromal depression. Special attention is given to the recruitment of African Americans because of well-documented inequalities in mental health services and depression treatment outcomes between races. A total of 306 subjects (half white, half African American) with scores of 16 or higher on the Center for Epidemiological Studies of Depression Scale, but with no history of major depressive disorder in the past 12 months, are being recruited and randomly assigned to either problem solving therapy-primary care or to a dietary education control condition. Time to, and rate of, incident episodes of major depressive disorder are to be modeled using survival analysis. Level of depressive symptoms will be analyzed via a mixed models approach. Twenty-two subjects have been recruited into the study, and to date eight have completed the randomly assigned intervention and postintervention assessment. Four of 22 have exited after developing major depressive episodes. None have complained about study procedures or demands. Implementation in a variety of community settings is going well. The data collected to date support the feasibility of translating from epidemiology to RCT design and implementation of empirical depression prevention research in later life.

Background: To compare the frequencies of risk factors, we describe risks for depression as a function of race among consecutively admitted participants in a randomized clinical trial of indicated depression prevention in later life. Methods: Seventy-two black and 143 white participants were screened for risk factors for depression. Results: Black participants were more likely to have fewer years of education and lower household income. They were more likely to be obese, live alone, experience functional disability, have a history of alcohol and drug abuse, and have lower scores on the Mini-mental State Examination and the Executive Interview (EXIT). White participants were not found to have greater prevalence or higher mean score on any risk factor. On average, black participants experienced approximately one more risk factor than white participants (t(213) = 3.32, p = 0.0011). Conclusions: In our sample, black participants had higher frequencies of eight risk factors for depression and a greater mean number of risk factors compared to white participants.

The objective of this study was to describe the correlates of prior antidepressant exposure and its association with response to protocolized treatment in older patients with major depression. Based on their prior antidepressant treatment exposure, 193 elderly patients with a major depressive episode were divided into three groups: those with no prior treatment for their current episode (not treated [TN]), those with antidepressant trials of inadequate dose or duration (“treatment-inadequate” [TI]), and those with at least one adequate trial but persisting depression (“treatment-resistant” [TR]). All patients then received protocolized treatment with interpersonal psychotherapy (IPT) and paroxetine plus pharmacologic augmentation if needed. The demographic, clinical, and outcome information were compared among these three groups. Approximately one-third of the patients referred to the study had been adequately treated (TR), one-third had been inadequately treated (TI), and one-third were not treated for the current episode (TN). Treatment completion rates and reasons for dropping out did not differ statistically among TR, TI, and TN patients. TR patients took longer to respond (13.0 weeks) than either TI or TN patients (7.6 and 8.0 weeks, respectively). TR and TI patients had lower response rates (67% and 71%) than TN patients (86%). Prior treatment exposure is an important correlate of course and outcome in late-life depression. Most TR and TI patients eventually respond, but TR patients may require more intensive and longer courses of treatment than TI and TN patients.

In two trials involving preterm infants, an oxygen-saturation target of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years but in significantly increased risks of the combined outcome and of death alone in post hoc combined analyses. The determination of the range of oxygen saturation that minimizes the competing risks of death, retinopathy of prematurity, and later disability in preterm infants is important. 1 , 2 The U.K. and Australian Benefits of Oxygen Saturation Targeting (BOOST)–II trials are two of five comparative effectiveness trials of the targeting of oxygen saturation in infants born before 28 weeks’ gestation. 3 – 8 These trials, known collectively as the Neonatal Oxygen Prospective Meta-analysis (NeOProM) Collaboration, were designed to compare the effects of a lower oxygen-saturation target range (85 to 89%) versus a higher target range (91 to 95%) on a primary outcome of death . . .