High-Dose Docosahexaenoic Acid in Newborns Born at Less Than 29 Weeks' Gestation and Behavior at Age 5 Years: Follow-Up of a Randomized Clinical Trial.

Importance: Children born at less than 29 weeks' gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain. Objective: To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks' gestation. Design, Setting and Participants: This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks' gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years' corrected age. Interventions: Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Main Outcomes and Measures: The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child's behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention. Results: Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, -0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health. Conclusions and Relevance: In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks' gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation. Trial Registration: Australian New Zealand Clinical Trial Registry: ACTRN12612000503820.

Development of a joint set of database parameters for the EU-ROP and Fight Childhood Blindness! ROP Registries.

BACKGROUND/AIMS: The incidence of retinopathy of prematurity (ROP) is increasing and treatment options are expanding, often without accompanying safety data. We aimed to define a minimal, patient-centred data set that is feasible to collect in clinical practice and can be used collaboratively to track and compare outcomes of ROP treatment with a view to improving patient outcomes. METHODS: A multinational group of clinicians and a patient representative with expertise in ROP and registry development collaborated to develop a data set that focused on real-world parameters and outcomes that were patient centred, minimal and feasible to collect in routine clinical practice. RESULTS: For babies receiving ROP treatment, we recommend patient demographics, systemic comorbidities, ROP status, treatment details, ophthalmic and systemic complications of treatment, ophthalmic and neurodevelopmental outcomes at initial treatment, any episodes of retreatment and follow-up examinations in the short and long-term to be collected for use in ROP studies, registries and routine clinical practice. CONCLUSIONS: We recommend these parameters to be used in registries and future studies of ROP treatment, to reduce the variation seen in previous reports and allow meaningful assessments and comparisons. They form the basis of the EU-ROP and the Fight Childhood Blindness! ROP Registries.

Language outcomes at 4 years of linguistically diverse children born very preterm: an Australian retrospective single-centre study.

BACKGROUND: Very 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. METHODS: Very 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. RESULTS: One 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. CONCLUSIONS: In 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.

Protocol for assessing if behavioural functioning of infants born <29 weeks' gestation is improved by omega-3 long-chain polyunsaturated fatty acids: follow-up of a randomised controlled trial.

INTRODUCTION: During the last trimester of pregnancy, the fetal brain undergoes a rapid growth spurt and accumulates essential nutrients including docosahexaenoic acid (DHA). This takes place ex-utero for infants born <29 weeks' gestation, without the in-utero provisions of DHA. Infants born <29 weeks' are more likely to experience behavioural and emotional difficulties than their term-born counterparts. It has been hypothesised that supplementing preterm infants with dietary DHA may alleviate insufficiency and subsequently prevent or minimise behavioural problems. This protocol describes a follow-up of infants born <29 weeks gestation who were enrolled in a randomised controlled trial (RCT) of DHA supplementation. We aim to determine whether DHA supplementation improves the behaviour, and general health of these infants. METHODS AND ANALYSIS: Infants born <29 weeks' gestation were enrolled in a multicentre blinded RCT of enteral DHA supplementation. Infants were randomised to receive an enteral emulsion that provided 60 mg/kg/day of DHA or a control emulsion commenced within the first 3 days of enteral feeding, until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Families of surviving children (excluding those who withdrew from the study) from the Australian sites (up to 955) will be invited to complete a survey. The survey will include questions regarding child behavioural and emotional functioning, executive functioning, respiratory health and general health. We hypothesise that the DHA intervention will have a benefit on the primary outcome, parent-rated behaviour and emotional status as measured using the Total Difficulties score of the Strengths and Difficulties Questionnaire. Detecting a 2-point difference between groups (small effect size of 0.25 SD) with 90% power will require follow-up of 676 participants. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/16/WCHN/184). Results will be disseminated in peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12612000503820.

A Two-Tiered Strategy for Preventing Complications of Bereavement in the First Thirteen Months Post-Loss: A Pilot Study Using Peer Supports with Professional Therapist Back-up.

This feasibility and acceptance pilot study for preventing complications of bereavement within the first year post loss recruited 20 adult grievers within 9 months of becoming bereft and assigned consenting subjects to peer supporters trained by a non-profit bereavement support organization for weekly or bi-weekly telephone-based peer support until month 13 post-loss. Subjects who met DSM-5 criteria for major depressive disorder or showed an Inventory of Complicated Grief (ICG) score exceeding 19, 6 months or more post loss, were assigned to 12 to 16 weeks of interpersonal psychotherapy (IPT) with an experienced therapist. Eight and six subjects completed the protocol assigned to peer support and IPT, respectively, with pre/post Patient Health Questionnaire-9 scores of 5.38 (2.45) versus 3.25 (4.13) (p = 0.266) and 16.67 (7.17) versus 8.40 (5.73) (p =0.063); and pre/post ICG scores of 12.50 (4.72) versus 5.00 (2.51) (p = 0.016) and 35.17 (5.12) versus 8.4 (5.73) (p = 0.063). Implications of this two-tiered model of early intervention for preventing complications of grief are discussed.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants.

BACKGROUND: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants.

BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: 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.

Depression Remission Rates Among Older Black and White Adults: Analyses From the IRL-GREY Trial.

OBJECTIVE: This study explored whether older black and white adults with major depressive disorder differed in rates of remission or attrition during open-label treatment with venlafaxine and supportive care. METHODS: A total of 47 black (10%) and 412 white (90%) adults age ≥60 were treated with open-label venlafaxine extended-release (≤300 mg per day) for 12-14 weeks during the initial phase of an multisite, randomized, placebo-controlled augmentation trial. Participants were help-seeking older adults with nonpsychotic major depressive disorder (single or recurrent episode) referred from specialty clinics, primary care practices, advertisements, and research programs. Remission was defined as a Montgomery-Asberg Depression Rating Scale score of ≤10 for two consecutive assessments at the end of 12 weeks. Kaplan-Meier curves displayed time to dropout and time to initial remission. Cox proportional hazards models assessed differences in attrition and remission rates. RESULTS: Black participants had greater baseline general medical comorbidity, worse physical health-related quality of life, and poorer cognitive function than white participants. White participants were more likely to have received an adequate trial of antidepressant and psychotherapy before study entry. Baseline depression severity, depression duration, age at onset, and recurrence history did not differ between groups. The groups had similar final doses of venlafaxine and similar rates of attrition and remission. Side-effect profiles were comparable between the groups. CONCLUSIONS: Despite greater medical comorbidity, lower cognitive function, and less adequate prior exposure to antidepressant treatment and psychotherapy, black participants were no more likely to discontinue antidepressant pharmacotherapy and experienced a rate of remission comparable to white participants.

Early intervention to preempt major depression among older black and white adults.

OBJECTIVE: The study objective was to assess the efficacy of problem-solving therapy for primary care (PST-PC) for preventing episodes of major depression and mitigating depressive symptoms of older black and white adults. The comparison group received dietary coaching. METHODS: A total of 247 participants (90 blacks, 154 whites, and three Asians) with subsyndromal depressive symptoms were recruited into a randomized depression prevention trial that compared effects of individually delivered PST-PC and dietary coaching on time to major depressive episode and level of depressive symptoms (Beck Depression Inventory) over two years. Cumulative intervention time averaged 5.5-6.0 hours in each study arm. RESULTS: The two groups did not differ significantly in time to major depressive episodes, and incidence of such episodes was low (blacks, N=8, 9%; whites, N=13, 8%), compared with published rates of 20%-25% over one year among persons with subsyndromal symptoms and receiving care as usual. Participants also showed a mean decrease of 4 points in depressive symptoms, sustained over two years. Despite greater burden of depression risk factors among blacks, no significant differences from whites were found in the primary outcome. CONCLUSIONS: Both PST-PC and dietary coaching are potentially effective in protecting older black and white adults with subsyndromal depressive symptoms from developing episodes of major depression over two years. Absent a control for concurrent usual care, this conclusion is preliminary. If confirmed, both interventions hold promise as scalable, safe, nonstigmatizing interventions for delaying or preventing episodes of major depression in the nation's increasingly diverse older population.

Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants.

OBJECTIVE: Not many large studies have reported the true impact of lower-grade intraventricular hemorrhages in preterm infants. We studied the neurodevelopmental outcomes of extremely preterm infants in relation to the severity of intraventricular hemorrhage. METHODS: A regional cohort study of infants born at 23 to 28 weeks' gestation and admitted to a NICU between 1998 and 2004. Primary outcome measure was moderate to severe neurosensory impairment at 2 to 3 years' corrected age defined as developmental delay (developmental quotient >2 SD below the mean), cerebral palsy, bilateral deafness, or bilateral blindness. RESULTS: Of the 1472 survivors assessed, infants with grade III-IV intraventricular hemorrhage (IVH; n = 93) had higher rates of developmental delay (17.5%), cerebral palsy (30%), deafness (8.6%), and blindness (2.2%). Grade I-II IVH infants (n = 336) also had increased rates of neurosensory impairment (22% vs 12.1%), developmental delay (7.8% vs 3.4%), cerebral palsy (10.4% vs 6.5%), and deafness (6.0% vs 2.3%) compared with the no IVH group (n = 1043). After exclusion of 40 infants with late ultrasound findings (periventricular leukomalacia, porencephaly, ventricular enlargement), isolated grade I-II IVH (n = 296) had increased rates of moderate-severe neurosensory impairment (18.6% vs 12.1%). Isolated grade I-II IVH was also independently associated with a higher risk of neurosensory impairment (adjusted odds ratio 1.73, 95% confidence interval 1.22-2.46). CONCLUSIONS: Grade I-II IVH, even with no documented white matter injury or other late ultrasound abnormalities, is associated with adverse neurodevelopmental outcomes in extremely preterm infants.

Nosocomial pulmonary tuberculosis contact investigation in a neonatal intensive care unit.

The diagnosis of smear-positive pulmonary tuberculosis in a medical officer working in a metropolitan Australian neonatal intensive care unit led to a contact investigation involving 125 neonates, 165 relatives, and 122 healthcare workers with varying degrees of exposure. There was no evidence of nosocomial tuberculosis transmission from the index case.

Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy.

CONTEXT: Cognitive impairment in late-life depression is a core feature of the illness. OBJECTIVE: To test whether donepezil hydrochloride and antidepressant therapy is superior to placebo and antidepressant therapy in improving cognitive performance and instrumental activities of daily living and in reducing recurrences of depression over 2 years of maintenance treatment. DESIGN: Randomized, double-blind, placebo-controlled maintenance trial. SETTING: University clinic. PARTICIPANTS: One hundred thirty older adults aged 65 years and older with recently remitted major depression. INTERVENTIONS: Random assignment to maintenance antidepressant pharmacotherapy and donepezil or to maintenance antidepressant pharmacotherapy and placebo. MAIN OUTCOME MEASURES: Global neuropsychological performance, cognitive instrumental activities of daily living, and recurrent depression. RESULTS: Donepezil and antidepressant therapy temporarily improved global cognition (treatment × time interaction, F2,216 = 3.78; P = .03), but effect sizes were small (Cohen d = 0.27, group difference at 1 year). A marginal benefit to cognitive instrumental activities of daily living was also observed (treatment × time interaction, F2,137 = 2.94; P = .06). The donepezil group was more likely than the placebo group to experience recurrent major depression (35% [95% confidence interval {CI}, 24%-46%] vs 19% [95% CI, 9%-29%], respectively; log-rank χ² = 3.97; P = .05; hazard ratio = 2.09 [95% CI, 1.00-4.41]). Post hoc subgroup analyses showed that of 57 participants with mild cognitive impairment, 3 of 30 participants (10% [95% CI, 0%-21%]) receiving donepezil and 9 of 27 participants (33% [95% CI, 16%-51%]) receiving placebo had a conversion to dementia over 2 years (Fisher exact test, P = .05). The mild cognitive impairment subgroup had recurrence rates of major depression of 44% with donepezil vs 12% with placebo (likelihood ratio = 4.91; P = .03). The subgroup with normal cognition (n = 73) showed no benefit with donepezil and no increase in recurrence of major depression. CONCLUSIONS: Whether a cholinesterase inhibitor should be used as augmentation in the maintenance treatment of late-life depression depends on a careful weighing of risks and benefits in those with mild cognitive impairment. In cognitively intact patients, donepezil appears to have no clear benefit for preventing progression to mild cognitive impairment or dementia or for preventing recurrence of depression. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00177671.

Treating depression to remission in older adults: a controlled evaluation of combined escitalopram with interpersonal psychotherapy versus escitalopram with depression care management.

OBJECTIVE: More than half of the older adults respond only partially to first-line antidepressant pharmacotherapy. Our objective was to test the hypothesis that a depression-specific psychotherapy, Interpersonal Psychotherapy (IPT), when used adjunctively with escitalopram, would lead to a higher rate of remission and faster resolution of symptoms in partial responders than escitalopram with depression care management (DCM). METHOD: We conducted a 16-week randomized clinical trial of IPT and DCM in partial responders to escitalopram, enrolling 124 outpatients aged 60 and older. The primary outcome, remission, was defined as three consecutive weekly scores of 7 or less on the Hamilton rating scale for depression (17-item). We conducted Cox regression analyses of time to remission and logistic modeling for rates of remission. We tested group differences in Hamilton depression ratings over time via mixed-effects modeling. RESULTS: Remission rates for escitalopram with IPT and with DCM were similar in intention-to-treat (IPT vs. DCM: 58 [95% CI: 46, 71] vs. 45% [33,58]; p = 0.14) and completer analyses (IPT vs. DCM: 58% [95% CI: 44,72] vs. 43% [30,57]; p = 0.20). Rapidity of symptom improvement did not differ in the two treatments. CONCLUSION: No added advantage of IPT over DCM was shown. DCM is a clinically useful strategy to achieve full remission in about 50% of partial responders.

A comparison of the frequencies of risk factors for depression in older black and white participants in a study of indicated prevention.

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.

Preventing depression in later life: translation from concept to experimental design and implementation.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Recovery from major depression in older adults receiving augmentation of antidepressant pharmacotherapy.

OBJECTIVE: Few data are available concerning the utility of augmentation in late-life depression treatment. The authors examined likelihood, speed, and predictors of recovery in older adults receiving augmentation pharmacotherapy after inadequate response to standardized treatment with paroxetine plus interpersonal psychotherapy. METHOD: Depression levels were monitored during open treatment in 195 adults age 70 or older. Patients were grouped by whether they required augmentation (bupropion, nortriptyline, or lithium) and compared on likelihood, time, and predictors of recovery. RESULTS: Augmentation was required for 105 patients (53.8%) because of inadequate treatment response (N=77) or response followed by relapse (N=28). Of these patients, 69 received augmentation and 36 did not (primarily because of consent withdrawal or comorbid medical conditions). Patients receiving augmentation showed lower recovery rates than patients never requiring augmentation: recovery occurred in 50.0% of patients receiving it because of inadequate response, 66.7% of those receiving it after early relapse, and 86.7% of patients never requiring augmentation. Patients receiving augmentation because of inadequate response recovered more slowly, with modestly more side effects than other patients. Greater medical burden and anxiety predicted slower recovery. CONCLUSIONS: Despite a lower likelihood of recovery in elderly people receiving augmentation, the recovery by over one-half of such patients suggests the value of augmentation for those able to tolerate it. Need for augmentation presages slower recovery in patients showing initial inadequate response; those requiring it after early relapse recovered more quickly. Strategies to further improve the likelihood and speed of recovery after initial treatment failure are needed.

Predicting 6-week treatment response to escitalopram pharmacotherapy in late-life major depressive disorder.

OBJECTIVE: Approximately half of older patients treated for major depressive disorder (MDD) do not achieve symptomatic remission and functional recovery with first-line pharmacotherapy. This study aims to characterize sociodemographic, clinical, and neuropsychologic correlates of full, partial, and non-response to escitalopram monotherapy of unipolar MDD in later life. METHODS: One hundred and seventy-five patients aged 60 and older were assessed at baseline on demographic variables, depression severity, hopelessness, anxiety, cognitive functioning, co-existing medical illness burden, social support, and quality of life (disability). Subjects received 10 mg/d of open-label escitalopram and were divided into full (n = 55; 31%), partial (n = 75; 42.9%), and non-responder (n = 45; 25.7%) groups based on Hamilton depression scores at week 6. Univariate followed by multivariate analyses tested for differences between the three groups. RESULTS: Non-responders to treatment were found to be more severely depressed and anxious at baseline than both full and partial responders, more disabled, and with lower self-esteem than full responders. In general partial responders resembled full responders more than they resembled non-responders. In multivariate models, more severe anxiety symptoms (both psychological and somatic) and lower self-esteem predicted worse response status at 6 weeks. CONCLUSION: Among treatment-seeking elderly persons with MDD, higher anxiety symptoms and lower self-esteem predict poorer response after six weeks of escitalopram treatment.

Developmental outcomes at the age of two years for very premature babies managed with nasal prong continuous positive airway pressure.

AIMS: To describe the developmental progress of very premature babies at the age of 2 years, who were managed in an era where nasal prong continuous positive airway pressure (CPAP) was the preferred method for the management of initial respiratory disease. METHODS: Two groups of very premature babies of <32 weeks gestation were compared, the first being managed with an intubation and mandatory ventilation approach, and the second being managed with a CPAP approach. The groups are compared with regard to the presence of brain injury, retinopathy and requiring discharge home on oxygen and then at 2 years, for language impairment, non-ambulatory cerebral palsy and significant developmental delay. The study is designed as an audit of data collected prospectively and longitudinally for babies born from 1998 to 2002. RESULTS: A significant number of babies were successfully managed on CPAP in the second era and significantly fewer received post-natal steroids. The number being discharged home on oxygen, brain injury and retinopathy were similar in the two groups. Developmental outcome assessed at 2 years of age was the same in both eras. CONCLUSIONS: A CPAP approach to the management of initial respiratory disease in premature babies of less than 32 weeks gestation at birth is associated with no measurable developmental advantage or disadvantage at 2 years of age.