Novel CFTR variants identified during the first 3 years of cystic fibrosis newborn screening in California.

California uses a unique method to screen newborns for cystic fibrosis (CF) that includes gene scanning and DNA sequencing after only one California-40 cystic fibrosis transmembrane conductance regulator (CFTR) panel mutation has been identified in hypertrypsinogenemic specimens. Newborns found by sequencing to have one or more additional mutations or variants (including novel variants) in the CFTR gene are systematically followed, allowing for prospective assessment of the pathogenic potential of these variants. During the first 3 years of screening, 55 novel variants were identified. Six of these novel variants were discovered in five screen-negative participants and three were identified in multiple unrelated participants. Ten novel variants (c.2554_2555insT, p.F1107L, c.-152G>C, p.L323P, p.L32M, c.2883_2886dupGTCA, c.2349_2350insT, p.K114del, c.-602A>T, and c.2822delT) were associated with a CF phenotype (42% of participants were diagnosed at 4 to 25 months of age), whereas 26 were associated with CFTR-related metabolic syndrome to date. Associations with the remaining novel variants were confounded by the presence of other diseases or other mutations in cis or by inadequate follow-up. These findings have implications for how CF newborn screening and follow-up is conducted and will help guide which genotypes should, and which should not, be considered screen positive for CF in California and elsewhere.

Outcomes for youths from racial-ethnic minority groups in a quality improvement intervention for depression treatment.

OBJECTIVE: This study examined racial-ethnic differences in the impact of the Youth Partners in Care quality improvement intervention. The intervention was designed to improve access to evidence-based depression care, primarily cognitive-behavioral therapy and medication, through primary care. Previous analyses have shown that the quality improvement intervention was associated with improved depression and quality-of-life outcomes at the end of the six-month intervention period. METHODS: A randomized controlled trial comparing quality improvement and usual care for youths from diverse racial-ethnic groups from five health care organizations, including managed care, the public sector, and academic center clinics, was conducted. Depressed youths (N=325), who self-identified as black (N=59), Latino (N=224), and white (N=42), aged 13-21 years, were included in these analyses. To evaluate intervention effects within racial-ethnic groups, regression models were constructed, which adjusted for baseline and study site variation in depression symptoms, mental health status, satisfaction with mental health care, and mental health service utilization. RESULTS: Differential intervention effects were found across racial-ethnic groups. Black youths in the intervention group experienced significant reductions in depression symptoms and had higher rates of use of specialty mental health care at the six-month follow-up. Among Latino youths, the intervention was associated with significantly greater satisfaction with care. Intervention effects were weak among white youths. CONCLUSIONS: Quality improvement interventions may help to reduce disparities in mental health care for youths from racial-ethnic minority groups. (

Long-term benefits of short-term quality improvement interventions for depressed youths in primary care.

OBJECTIVE: Quality improvement programs for depressed youths in primary care settings have been shown to improve 6-month clinical outcomes, but longer-term outcomes are unknown. The authors examined 6-, 12-, and 18-month outcomes of a primary care quality improvement intervention. METHOD: Primary care patients 13-21 years of age with current depressive symptoms were randomly assigned to a 6-month quality improvement intervention (N=211) or to treatment as usual enhanced with provider training (N=207). The quality improvement intervention featured expert leader teams to oversee implementation of the intervention; clinical care managers trained in cognitive-behavioral therapy for depression to support patient evaluation and treatment; and support for patient and provider choice of treatments. RESULTS: The quality improvement intervention, relative to enhanced treatment as usual, lowered the likelihood of severe depression (Center for Epidemiological Studies Depression Scale score > or =24) at 6 months; a similar trend at 18 months was not statistically significant. Path analyses revealed a significant indirect intervention effect on long-term depression due to the initial intervention improvement at 6 months. CONCLUSIONS: In this randomized effectiveness trial of a primary care quality improvement intervention for depressed youths, the main effect of the intervention on outcomes was to decrease the likelihood of severe depression at the 6-month outcome assessment. These early intervention-related improvements conferred additional long-term protection through a favorable shift in illness course through 12 and 18 months.

Impact of pediatric critical illness and injury on families: a systematic literature review.

OBJECTIVE: We sought to inform decision-making for children and families by describing what is known and remains unknown about the impact of childhood critical illness and injury on families. This report also was designed as a tool for research planning and design so that meaningful studies are performed and duplication is avoided. DESIGN: After a national scholarship competition and the identification of 3 medical student summer scholars, a literature search was conducted by using the National Library of Medicine and a PubMed keyword search system at the National Institutes of Health. RESULTS: A total of 115 reports were reviewed and assigned to the 5 following categories characterizing the impact of pediatric critical illness/injury on families: stressors, needs, specific domains (psychological, physical, social), coping, and interventions. The reports reviewed indicate that pediatric critical illness and injury is stressful for the entire family. The effects on parents, siblings, and marital cohesion were variably described. Needs of family members (eg, rest, nutrition, communication) were identified as being unmet in many studies. Permanent impact on siblings and marital relationships has been considered detrimental, but these conclusions are not adequately quantified in presently available studies. Reviewed reports minimally investigated cultural diversity, effects on fathers versus mothers, siblings, socioeconomic status, and financial burden. Studies were often anecdotal and included small sample sizes. Methodologic limitations were numerous and varied and seriously narrowed the significance of the studies we reviewed. The reports that we evaluated were largely limited to those of English-speaking families, white people, and married mothers. CONCLUSIONS: Future research should use more rigorous methods in the measurement of impact of childhood critical illness and injury on families. Families of critically ill and injured children would benefit from the practitioners of pediatric critical care acquiring enhanced knowledge and sensitivity about family communication and dynamics.

Depression and role impairment among adolescents in primary care clinics.

PURPOSE: To evaluate the association between depression and role impairment in a primary care sample, with and without controlling for the effects of general medical conditions. METHODS: Cross-sectional survey of consecutive primary care patients, ages 13-21 years (n = 3471), drawn from six sites including public health, managed care, and academic health center clinics. We assessed probable depressive disorder, depressive symptoms, and common medical problems using youth self-report on a brief screening questionnaire. Main outcome measures were two indicators of role impairment: (a) decrement in productivity/role activity, defined as not in school or working full time; and (b) low educational attainment, defined as more than 2 years behind in school or > or = 20 years of age and failed to complete high school. RESULTS: Adolescents screening positive for probable depressive disorder had elevated rates of productivity/role activity decrements (19% vs. 13%; OR 1.69; 95% confidence interval [CI] 1.39-2.06; p < 0.001) and low educational attainment (20% vs. 15%; OR 1.47; 95% CI 1.21-1.78; p < 0.001). Probable depressive disorder made a unique contribution to the prediction of these impairment indicators after adjusting for the effect of having a general medical condition; controlling for depression, the presence of a general medical condition did not contribute to role impairment. CONCLUSIONS: Adolescent primary care patients screening positive for depression are at increased risk for impairment in school/work productivity and educational attainment. These findings emphasize the importance of primary care clinicians' attention to depression and role limitations.

Effectiveness of a quality improvement intervention for adolescent depression in primary care clinics: a randomized controlled trial.

CONTEXT: Depression is a common condition associated with significant morbidity in adolescents. Few depressed adolescents receive effective treatment for depression in primary care settings. OBJECTIVE: To evaluate the effectiveness of a quality improvement intervention aimed at increasing access to evidence-based treatments for depression (particularly cognitive-behavior therapy and antidepressant medication), relative to usual care, among adolescents in primary care practices. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted between 1999 and 2003 enrolling 418 primary care patients with current depressive symptoms, aged 13 through 21 years, from 5 health care organizations purposively selected to include managed care, public sector, and academic medical center clinics in the United States. INTERVENTION: Usual care (n = 207) or 6-month quality improvement intervention (n = 211) including expert leader teams at each site, care managers who supported primary care clinicians in evaluating and managing patients' depression, training for care managers in manualized cognitive-behavior therapy for depression, and patient and clinician choice regarding treatment modality. Participating clinicians also received education regarding depression evaluation, management, and pharmacological and psychosocial treatment. MAIN OUTCOME MEASURES: Depressive symptoms assessed by Center for Epidemiological Studies-Depression Scale (CES-D) score. Secondary outcomes were mental health-related quality of life assessed by Mental Health Summary Score (MCS-12) and satisfaction with mental health care assessed using a 5-point scale. RESULTS: Six months after baseline assessments, intervention patients, compared with usual care patients, reported significantly fewer depressive symptoms (mean [SD] CES-D scores, 19.0 [11.9] vs 21.4 [13.1]; P = .02), higher mental health-related quality of life (mean [SD] MCS-12 scores, 44.6 [11.3] vs 42.8 [12.9]; P = .03), and greater satisfaction with mental health care (mean [SD] scores, 3.8 [0.9] vs 3.5 [1.0]; P = .004). Intervention patients also reported significantly higher rates of mental health care (32.1% vs 17.2%, P<.001) and psychotherapy or counseling (32.0% vs 21.2%, P = .007). CONCLUSIONS: A 6-month quality improvement intervention aimed at improving access to evidence-based depression treatments through primary care was significantly more effective than usual care for depressed adolescents from diverse primary care practices. The greater uptake of counseling vs medication under the intervention reinforces the importance of practice interventions that include resources to enable evidence-based psychotherapy for depressed adolescents.