Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies.

PURPOSE: To compare the efficacy and safety of two long-acting dual bronchodilator combinations: indacaterol/glycopyrrolate (IND/GLY) versus umeclidinium/vilanterol (UMEC/VI). METHODS: Studies A2349 and A2350 were replicate, randomized, double-blind, double-dummy, active-controlled, cross-over studies in patients with moderate-to-severe COPD. Patients were randomized to sequential 12-week treatments of twice-daily IND/GLY 27.5/15.6 µg and once-daily UMEC/VI 62.5/25 µg, each separated by a 3-week washout. The primary objective was to demonstrate non-inferiority of IND/GLY compared with UMEC/VI in terms of the 24-h forced expiratory volume in 1 s profile at week 12 (FEV1 AUC0-24). Rescue medication use, symptom control, and safety were assessed throughout. RESULTS: Both treatments delivered substantial bronchodilation over 12 weeks, with improvements in FEV1 AUC0-24h at week 12 of 232 and 185 mL for IND/GLY, and 244 and 203 mL with UMEC/VI in Studies A2349 and A2350, respectively. The primary efficacy objective of non-inferiority of IND/GLY relative to UMEC/VI was not met as the lower bound of the confidence interval for the LS treatment comparison was below the pre-specified non-inferiority margin of -20 mL in both studies: -26.9 and -34.2 mL, respectively (LS mean between-treatment differences: -11.5 and -18.2 mL). Both drugs were well tolerated, with AE profiles consistent with their respective prescribing information. CONCLUSIONS: IND/GLY and UMEC/VI provided clinically meaningful and comparable bronchodilation. Non-inferiority of IND/GLY to UMEC/VI could not be declared although between-treatment differences were not clinically relevant. The data support the use of IND/GLY as an efficacious and well tolerated treatment option in patients with COPD. (ClinicalTrials.gov NCT02487446 and NCT02487498).

Long-term effects of the Family Bereavement Program on spousally bereaved parents: Grief, mental health problems, alcohol problems, and coping efficacy.

This study reports on the findings from a 6-year follow-up of a randomized trial of the Family Bereavement Program (FBP) on the outcomes for spousally bereaved parents. Spousally bereaved parents (N = 131) participated in the trial in which they were randomly assigned to receive the FBP (N = 72) or literature control (N = 59). Parents were assessed at four time points: pretest, posttest, and 11-month and 6-year follow-up. They reported on mental health problems, grief, and parenting at all four time periods. At the 6-year follow-up, parents reported on additional measures of persistent complex bereavement disorder, alcohol abuse problems, and coping efficacy. Bereaved parents in the FBP as compared to those in the literature control had lower levels of symptoms of depression, general psychiatric distress, prolonged grief, and alcohol problems, and higher coping efficacy (for mothers) at the 6-year follow-up. Multiple characteristics of the parent (e.g., gender, age, and baseline mental health problems) and of the spousal death (e.g., cause of death) were tested as moderators of program effects on each outcome, but only 3 of 45 tests of moderation were significant. Latent growth modeling found that the effects of the FBP on depression, psychiatric distress, and grief occurred immediately following program participation and were maintained over 6 years. Mediation analysis found that improvement in positive parenting partially mediated program effects to reduce depression and psychiatric distress, but had an indirect effect to higher levels of grief at the 6-year follow-up. Mediation analysis also found that improved parenting at the 6-year follow-up was partially mediated by program effects to reduce depression and that program effects to increase coping efficacy at the 6-year follow-up was partially mediated through reduced depression and grief and improved parenting. FBP reduced mental health problems, prolonged grief, and alcohol abuse, and increased coping efficacy of spousally bereaved parents 6 years later. Mediation pathways for program effects differed across outcomes at the 6-year follow-up.

FLIGHT1 and FLIGHT2: Efficacy and Safety of QVA149 (Indacaterol/Glycopyrrolate) versus Its Monocomponents and Placebo in Patients with Chronic Obstructive Pulmonary Disease.

RATIONALE: Current Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy recommends the combination of two long-acting bronchodilators of different pharmacologic classes for the management of chronic obstructive pulmonary disease (COPD) if symptoms are not adequately controlled by a single bronchodilator. OBJECTIVES: The FLIGHT1 and FLIGHT2 studies evaluated the efficacy and safety of QVA149 (indacaterol/glycopyrrolate), a fixed-dose combination of a long-acting ß2-agonist (indacaterol) and a long-acting muscarinic antagonist (glycopyrrolate), compared with its monocomponents and placebo in patients with moderate-to-severe COPD. METHODS: FLIGHT1 and FLIGHT2 were 12-week, identical, multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled studies. Patients were randomized (1:1:1:1) to indacaterol/glycopyrrolate (27.5/15.6 µg twice daily), indacaterol (27.5 µg twice daily), glycopyrrolate (15.6 µg twice daily), or placebo, all delivered via the Neohaler device. The primary objective was to demonstrate the superiority of indacaterol/glycopyrrolate versus its monocomponents for standardized area under the curve from 0-12 hours for FEV1 at Week 12. Secondary objectives included St. George's Respiratory Questionnaire total score and transition dyspnea index total score and reduction in daily rescue medication use with indacaterol/glycopyrrolate versus placebo. MEASUREMENTS AND MAIN RESULTS: In total, 2,038 patients were included in the pooled analysis. Indacaterol/glycopyrrolate was statistically superior in terms of FEV1 area under the curve from 0-12 hours compared with its monocomponents (P < 0.001). Statistically and clinically meaningful improvements in St. George's Respiratory Questionnaire total score, transition dyspnea index total score, and reduction in rescue medication use were observed with indacaterol/glycopyrrolate compared with placebo (P < 0.001). The safety profile was comparable across the treatment groups. CONCLUSIONS: Indacaterol/glycopyrrolate twice daily can be an alternative treatment option for the management of symptomatic patients with moderate-to-severe COPD. Clinical trial registered with www.clinicaltrials.gov (NCT 01727141 and NCT 0171251).

Longitudinal mediators of a randomized prevention program effect on cortisol for youth from parentally bereaved families.

We recently reported that a randomized controlled trial of a family-focused intervention for parentally bereaved youth predicted higher cortisol output 6 years later relative to a control group of bereaved youth (Luecken et al., Psychoneuroendocrinology 35, 785-789, 2010). The current study evaluated longitudinal mediators of the intervention effect on cortisol 6 years later. Parentally bereaved children (N = 139; mean age, 11.4; SD = 2.4; age range = 8-16 years; male; 61% Caucasian, 17% Hispanic, 7% African American, and 15% other ethnicities) were randomly assigned to the 12-week preventive intervention (n = 78) or a self-study control (n = 61) condition. Six years later (mean age, 17.5; SD, 2.4), cortisol was sampled as youth participated in a parent-child conflict interaction task. Using four waves of data across the 6 years, longitudinal mediators of the program impact on cortisol were evaluated. Program-induced increases in positive parenting, decreases in child exposure to negative life events, and lower externalizing symptoms significantly mediated the intervention effect on cortisol 6 years later.

Strengthening effective parenting practices over the long term: effects of a preventive intervention for parentally bereaved families.

This study tested the effect of the Family Bereavement Program (FBP), a preventive intervention for bereaved families, on effective parenting (e.g., caregiver warmth, consistent discipline) 6 years after program completion. Families (n = 101; 69% female caregivers; 77% Caucasian, 11% Hispanic) with children between ages 8 and 16 who had experienced the death of one parent were randomized to the FBP (n = 54) or a literature control condition (n = 47). Multiple regression analyses conducted within a multilevel framework indicated that the FBP had a significant positive impact on a multirater, multimeasure assessment of parenting at 6-year follow-up, controlling for pretest levels of parenting and child mental health problems. Mediation analyses showed that short-term program effects on parenting, including caregiver warmth and effective discipline, significantly mediated the impact of the FBP on effective parenting 6 years later. These findings indicate that a relatively cost-effective brief intervention for families who experienced a major stressor resulted in sustained effects on caregiver warmth and consistent discipline 6 years following the program.

Comparing cognitive, relational and stress mechanisms underlying gender differences in recovery from bereavement-related internalizing problems.

Four putative mediators underlying gender differences in youths' recovery from bereavement-related internalizing problems were examined in a sample (N = 109; age range = 8-16 years at the initial assessment) of parentally bereaved youth: intrusive thoughts about grief, postdeath stressors, negative appraisals of postdeath stressors, and fear of abandonment. A three-wave parallel process longitudinal growth model design was employed. Changes in internalizing problems and mediators were measured as a function of months since the death. Girls showed stability in depression symptoms and a slight rise in anxiety symptoms; boys' trajectories of symptoms of anxiety and depression declined. Girls' higher initial levels of postdeath stressors, threat appraisals and fear of abandonment mediated their higher level of internalizing problems 14 months later. Girls' higher initial fear of abandonment also mediated additional growth in anxiety relative to boys.

Evidence-Based Practices for Parentally Bereaved Children and Their Families.

Parental death is one of the most traumatic events that can occur in childhood, and several reviews of the literature have found that the death of a parent places children at risk for a number of negative outcomes. This article describes the knowledge base regarding both empirically-supported, malleable factors that have been shown to contribute to or protect children from mental health problems following the death of a parent and evidence-based practices to change these factors. In addition, nonmealleable factors clinicians should consider when providing services for children who have experienced the death of a parent are reviewed.

Three perspectives on mental health problems of young adults and their parents at a 15-year follow-up of the family bereavement program.

OBJECTIVE: Effects are reported of the Family Bereavement Program (FBP) on the mental health of bereaved youth and their surviving parent 15 years following the program. METHOD: On-hundred and 56 families (244 children ages 8-16; 54% male; 67% Non-Hispanic White) were randomly assigned to receive either the FBP (N = 90) or a literature control condition (N = 66). At the 15-year follow-up 80% of the youth and 76% of the bereaved parents were reinterviewed. Mental health problems and service use were self-reported by young adults and their parents. Key informants reported on mental health problems of young adults. RESULTS: Young adults in the FBP reported significantly less use of mental health services and of psychiatric medication than controls. Key informants reported significantly lower mental health problems for young adults who were in FBP as compared with controls and for those who were younger lower internalizing and externalizing problems for those in the FBP as compared with controls. Bereaved parents reported a significantly lower rate of alcoholism and less use of support groups than controls. CONCLUSIONS: The results provided evidence that FBP led to lower mental health problems and less service use by bereaved young adults and their parents as compared with controls. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Estimating the costs of preventive interventions.

The goal of this article is to improve the practice and reporting of cost estimates of prevention programs. It reviews the steps in estimating the costs of an intervention and the principles that should guide estimation. The authors then review prior efforts to estimate intervention costs using a sample of well-known but diverse studies. Finally, the authors illustrate the principles with an example, the Family Bereavement Program. They conclude that example by discussing whether and how the costs of the intervention might differ when implemented in a real-world setting.

Symptoms of internalizing and externalizing problems: modeling recovery curves after the death of a parent.

BACKGROUND: The death of a parent is a major family disruption that can place children at risk for later depression and other mental health problems. DESIGN: Theoretically based randomized controlled trial for parentally bereaved children. SETTING/PARTICIPANTS: Two-hundred and forty-four children and adolescents and their caregivers from 156 families were randomly assigned to the Family Bereavement Program (FBP) intervention condition (90 families; 135 children) or to a control condition (66 families; 109 children). Data collection occurred from 1996 to 1998. INTERVENTION: Children and caregivers in the intervention condition met separately for 12 two-hour weekly sessions. Skills targeted by the program for children included positive coping, stress appraisals, control beliefs, and self-esteem. The caregiver program targeted caregiver mental health, life stressors, and improved discipline in the home. Both child and caregiver programs focused on improved quality of the caregiver-child relationship. MAIN OUTCOME MEASURES: Child and caregiver reports of internalizing and externalizing symptoms. RESULTS: Longitudinal growth curve modeling was performed to model symptoms over time from the point of parental death. The rate of recovery for girls in the program condition was significantly different from that of girls in the control condition across all outcomes. Boys in both conditions showed reduced symptoms over time. CONCLUSIONS: The methodology offers a conceptually unique way of assessing recovery in terms of reduced mental health problems over time after an event and has contributed to further understanding of FBP intervention effects. The intervention program facilitated recovery among girls, who did not show reduction in behavior problems without the program, while boys demonstrated decreased symptoms even without intervention.

Stressors, quality of the child-caregiver relationship, and children's mental health problems after parental death: the mediating role of self-system beliefs.

Investigated whether three self-system beliefs, fear of abandonment, coping efficacy, and self-esteem, mediated the relations of stressors and caregiver-child relationship quality with concurrent and prospective internalizing and externalizing problems in a sample of children who had experienced parental death in the previous 2.5 years. The cross-sectional sample consisted of 340 children ages 7-16 and their surviving parent/current caregiver; the longitudinal analyses employed a subset of this sample that consisted of 100 children and their parents/caregivers who were assessed at three time points. A multirater, multimethod measure of caregiver-child relationship quality and a multirater measure of children's mental health problems were used. The cross-sectional model supported a mediational relation for fear of abandonment, coping efficacy, and self-esteem. The three-wave longitudinal model showed that fear of abandonment at Time 2 mediated the relation between stressors at Time 1 and internalizing and externalizing problems at Time 3. Implications of these findings for understanding the development of mental health problems in parentally bereaved children and designing interventions for this at-risk group are discussed.

The Effects of the Family Bereavement Program to Reduce Suicide Ideation and/or Attempts of Parentally Bereaved Children Six and Fifteen Years Later.

Findings concerning the long-term effects of the Family Bereavement Program (FBP) to reduce suicide ideation and/or attempts of parentally bereaved children and adolescents are presented. Parental death is a significant risk factor for suicide among offspring (Guldin et al., 2015). This study is a long-term follow-up of 244 children and adolescents who had participated in a randomized trial of the FBP, examining the intervention effects on suicide ideation and/or attempts as assessed through multiple sources. Results indicate a significant effect of the FBP to reduce suicide ideation and/or attempts at the 6- and 15-year follow-up evaluation. The findings support the potential benefits of further research on "upstream" suicide prevention.

The family bereavement program: efficacy evaluation of a theory-based prevention program for parentally bereaved children and adolescents.

This article presents an experimental evaluation of the Family Bereavement Program (FBP), a 2-component group intervention for parentally bereaved children ages 8-16. The program involved separate groups for caregivers, adolescents, and children, which were designed to change potentially modifiable risk and protective factors for bereaved children. The evaluation involved random assignment of 156 families (244 children and adolescents) to the FBP or a self-study condition. Families participated in assessments at pretest, posttest, and 11-month follow-up. Results indicated that the FBP led to improved parenting, coping, and caregiver mental health and to reductions in stressful events at posttest. At follow-up, the FBP led to reduced internalizing and externalizing problems, but only for girls and those who had higher problem scores at baseline.

Family Bereavement Program (FBP) Approach to Promoting Resilience Following the Death of a Parent.

This paper describes a research-based program designed to promote resilience of parentally-bereaved children and their bereaved surviving parent. A contextual resilience model is described as the conceptual foundation of the program. The program is designed to enhance specific parenting and coping skills and to help caregivers and children accomplish goals they set for themselves at the outset of the program. The content of the twelve-sessions and the approach to teaching and supporting parents work on their program and personal goals are described. Evaluation of the program using a randomized experimental design indicates that the program is effective in promoting resilient outcomes of children and of the bereaved parent six-years following their participation in the program.

The Family Bereavement Program: description of a theory-based prevention program for parentally-bereaved children and adolescents.

This article describes a preventive intervention to promote resilience of parentally bereaved youth. This intervention includes separate but concurrent programs for youth and caregivers that were developed to change empirically-supported risk and protective factors. We first discuss the risk that parental death confers to youth mental health and social adaptation outcomes. Next, we discuss the theoretical framework underlying this program. After describing the content and structure of the program, we describe the results of an experimental field trial and discuss directions for future work.

The effectiveness of various models of primary care-based follow-up after stroke: a systematic review.

AIM: To systematically review studies reporting the effectiveness of various models of follow-up in primary care on a range of outcomes (physical, psychological, social functioning, or quality of life) for survivors of stroke and their caregivers. BACKGROUND: Stroke is a major cause of disability globally. Current UK policy calls for a primary care-based review of healthcare and social-care needs at six weeks and six months after hospital discharge and then annually. METHODS: Trials meeting the pre-defined inclusion criteria were identified by the systematic searching of electronic databases. Data were extracted by two independent researchers. Studies were rated using the McMaster University Quality Assessment Tool. FINDINGS: Nine randomised controlled trials that met the inclusion criteria were identified. These studies included interventions using stroke support workers, care coordinators or case managers. The methodological quality of the studies was variable, and models of care demonstrated inconsistent working relationships with general practitioners. Patients and caregivers receiving formal primary care-based follow-up did not show any gains in physical function, mood, or quality of life when compared with those who did not. Patients and caregivers receiving follow-up were generally more satisfied with some aspects of communication, and had a greater knowledge of stroke. CONCLUSIONS: The limited quality of these studies and the lack of a sound theoretical basis for the development of interventions together highlight the urgent need for high-quality research studies in this area.

Long-term effects of the family bereavement program on multiple indicators of grief in parentally bereaved children and adolescents.

OBJECTIVES: This article reports on results from a randomized experimental trial of the effects of the Family Bereavement Program (FBP) on multiple measures of grief experienced by parentally bereaved children and adolescents over a 6-year period. METHOD: Participants were 244 youths (ages 8-16, mean age = 11.4 years) from 156 families that had experienced the death of a parent. The sample consisted of 53% boys and 47% girls; ethnicity was 67% non-Hispanic White and 33% ethnic minority. Families were randomly assigned to the FBP (N = 135) or a literature control condition (N = 109). Two grief measures, the Texas Revised Inventory of Grief and the Intrusive Grief Thoughts Scale (IGTS) were administered at 4 times over 6 years: pretest, posttest, and 11-month and 6-year follow-ups. A 3rd measure, an adaptation of the Inventory of Traumatic Grief (ITG) was administered only at the 6-year follow-up. RESULTS: Compared with the control group, the FBP group showed a greater reduction in their level of problematic grief (IGTS) at posttest and 6-year follow-up and in the percentage at clinical levels of problematic grief at the posttest. The FBP also reduced scores on a dimension of the ITG, Social Detachment/Insecurity, at 6-year follow-up for 3 subgroups: those who experienced lower levels of grief at program entry, older youths, and boys. CONCLUSION: These are the first findings from a randomized trial with long-term follow-up of the effects of a program to reduce problematic levels of grief of parentally bereaved youths.

Cortisol levels six-years after participation in the Family Bereavement Program.

Recent studies have found short-term adrenocortical benefits of early interventions for at-risk children. The current study evaluated the effects of the Family Bereavement Program on cortisol levels six years after the program. Parentally bereaved children were randomly assigned to the 12-week preventive intervention (n=78) or a self-study control (n=61) condition. Six years later (mean age 17.5), salivary cortisol levels were measured before and after a conflict discussion task conducted in late afternoon/early evening. The intervention group had significantly higher cortisol levels across the task compared to the control group, and lower cortisol was associated with higher externalizing symptoms. The group effect did not differ by age at the time of death, and the group difference remained significant after adjustment for pre-intervention mental health and current mental health symptoms. Results suggest that a family-focused intervention for parentally bereaved youth may have prevented the development of attenuated cortisol secretion suggestive of dysregulation and associated with externalizing problems.

Six-year follow-up of a preventive intervention for parentally bereaved youths: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of the Family Bereavement Program (FBP) to prevent mental health problems in parentally bereaved youths and their parents 6 years later. DESIGN: Randomized controlled trial. SETTING: Arizona State University Prevention Research Center from November 2002 to July 2005. PARTICIPANTS: Two hundred eighteen bereaved youths (89.34% of 244 enrolled in the trial 6 years earlier) and 113 spousally bereaved parents. INTERVENTIONS: The FBP includes 12 group sessions for caregivers and youths; the literature control (LC) condition includes bereavement books for youths and caregivers. MAIN OUTCOME MEASURES: Comparisons of youths in the FBP and LC on a measure of mental disorder diagnosis, 5 measures of mental health problems, and 4 measures of competent functioning; and comparisons of spousally bereaved parents on 2 measures of mental health problems. RESULTS: Youths in the FBP as compared with those in the LC had significantly lower externalizing problems as reported by caregivers and youths (adjusted mean, -0.06 vs 0.13, respectively; P = .02) and on teacher reports of externalizing problems (adjusted mean, 52.69 vs 56.27, respectively; P = .001) and internalizing problems (adjusted mean, 47.29 vs 56.27, respectively; P = .002), and they had higher self-esteem (adjusted mean, 33.93 vs 31.91, respectively; P = .005). Parents in the FBP had lower depression scores than those in the LC (adjusted mean, 5.48 vs 7.83, respectively; P = .04). A significant moderated program effect indicated that for youths with lower baseline problems, the rate of diagnosed mental disorder was lower for those in the FBP than in the LC. CONCLUSION: This study demonstrates efficacy of the FBP to reduce mental health problems of bereaved youths and their parents 6 years later. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01008189.