The North Carolina Experience with Mucopolysaccharidosis Type I Newborn Screening.

OBJECTIVE: To evaluate the performance of a 2-tiered newborn screening method for mucopolysaccharidosis type I (MPS I) in North Carolina. STUDY DESIGN: The screening algorithm included a flow injection analysis-tandem mass spectrometry assay as a first-tier screening method to measure α-L-iduronidase (IDUA) enzyme activity and Sanger sequencing of the IDUA gene on dried blood spots as a second-tier assay. The screening algorithm was revised to incorporate the Collaborative Laboratory Integrated Reports, an analytical interpretive tool, to reduce the false-positive rate. A medical history, physical examination, IDUA activity, and urinary glycosaminoglycan (GAG) analysis were obtained on all screen-positive infants. RESULTS: A total of 62 734 specimens were screened with 54 screen-positive samples using a cut-off of 15% of daily mean IDUA activity. The implementation of Collaborative Laboratory Integrated Reports reduced the number of specimens that screened positive to 19 infants. Of the infants identified as screen-positive, 1 had elevated urinary GAGs and a homozygous pathogenic variant associated with the severe form of MPS I. All other screen-positive infants had normal urinary GAG analysis; 13 newborns had pseudodeficiency alleles, 3 newborns had variants of unknown significance, and 2 had heterozygous pathogenic variants. CONCLUSIONS: An infant with severe MPS I was identified and referred for a hematopoietic stem cell transplant. Newborn IDUA enzyme deficiency is common in North Carolina, but most are due to pseudodeficiency alleles in infants with normal urinary GAG analysis and no evidence of disease. The pilot study confirmed the need for second-tier testing to reduce the follow-up burden.

Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Five to ten percent of individuals with latent tuberculosis infection (LTBI) progress to active tuberculosis (TB) disease. Identifying and treating LTBI is a key component of the strategy for reducing the burden of TB disease. OBJECTIVE: To review the evidence about targeted screening and treatment for LTBI among adults in primary care settings to support the US Preventive Services Task Force in updating its 1996 recommendation. DATA SOURCES: MEDLINE, Cochrane Library, and trial registries, searched through August 3, 2015; references from pertinent articles; and experts. Literature surveillance was conducted through May 31, 2016. STUDY SELECTION: English-language studies of LTBI screening, LTBI treatment with recommended pharmacotherapy, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of individuals for whom LTBI screening and treatment is part of public health surveillance or disease management were excluded. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles. When at least 3 similar studies were available, random-effects meta-analysis was used to generate pooled estimates of outcomes. MAIN OUTCOMES AND MEASURES: Sensitivity, specificity, reliability, active TB disease, mortality, hepatotoxicity, and other harms. RESULTS: The review included 72 studies (n = 51 711). No studies evaluated benefits and harms of screening compared with no screening. Pooled estimates for sensitivity of the TST at both 5-mm and 10-mm induration thresholds were 0.79 (5-mm: 95% CI, 0.69-0.89 [8 studies, n = 803]; 10 mm: 95% CI, 0.71-0.87 [11 studies; n = 988]), and those for IGRAs ranged from 0.77 to 0.90 (57 studies; n = 4378). Pooled estimates for specificity of the TST at the 10-mm and 15-mm thresholds and for IGRAs ranged from 0.95 to 0.99 (34 studies; n = 23 853). A randomized clinical trial (RCT) of 24 weeks of isoniazid in individuals with pulmonary fibrotic lesions and LTBI (n = 27 830) found a reduction in absolute risk of active TB at 5 years from 1.4% to 0.5% (relative risk [RR], 0.35 [95% CI, 0.24-0.52]) and an increase in absolute risk for hepatoxicity from 0.1% to 0.5% (RR, 4.59 [95% CI, 2.03-10.39]) for 24 weeks of daily isoniazid compared with placebo. An RCT (n = 6886) found that 3 months of once-weekly rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing active TB. The risk difference for hepatoxicity comparing isoniazid with rifampin ranged from 3% to 7%, with a pooled RR of 3.29 (95% CI, 1.72-6.28 [3 RCTs; n = 1327]). CONCLUSIONS AND RELEVANCE: No studies evaluated the benefits and harms of screening compared with no screening. Both the TST and IGRAs are moderately sensitive and highly specific within countries with low TB burden. Treatment reduced the risk of active TB among the populations included in this review. Isoniazid is associated with higher rates of hepatotoxicity than placebo or rifampin.

Use of antipsychotic medications in pediatric and young adult populations: future research needs.

The use of antipsychotics, particularly second generation antipsychotics, among children and adolescents has increased markedly during the past 20 years. Existing evidence gaps make this practice controversial and hinder treatment decision-making. This article describes and prioritizes future research needs regarding antipsychotic treatment in youth, focusing on within-class and between-class drug comparisons with regard to key population subgroups, efficacy and effectiveness outcomes, and adverse event outcomes. Using as a foundation a recent systematic review of antipsychotic treatment among youth, which was completed by a different Evidence-based Practice Center, we worked with a diverse group of 12 stakeholders representing researchers, funders, health care providers, patients, and families to identify and prioritize research needs. From an initial list of 16 evidence gaps, we enumerated 6 high-priority research needs: 1) long-term comparative effectiveness across all psychiatric disorders; 2) comparative long-term risks of adverse outcomes; 3) short-term risks of adverse events; 4) differentials of efficacy, effectiveness, and safety for population subgroups; 5) comparative effectiveness among those with attention-deficit/hyperactivity disorder and disruptive behavior disorders and common comorbidities; 6) comparative effectiveness among those with bipolar disorder and common comorbidities. In this article, we describe these future research needs in detail and discuss study designs that could be used to address them.

Attention-deficit/hyperactivity disorder: identifying high priority future research needs.

With onset often occurring before 6 years of age, attention-deficit/hyperactivity disorder (ADHD) involves attention problems, impulsivity, overactivity, and sometimes disruptive behavior. Impairment usually persists into adulthood, with an estimated worldwide prevalence in adults of 2.5%. Existing gaps in evidence concerning ADHD hinder decision-making about treatment. This article describes and prioritizes future research needs for ADHD in three areas: treatment effectiveness for at-risk preschoolers; long-term treatment effectiveness; and variability in prevalence, diagnosis, and treatment.Using a recent systematic review concerning ADHD completed by a different evidence-based practice center as a foundation, we worked with a diverse group of 12 stakeholders, who represented researchers, funders, healthcare providers, patients, and families, to identify and prioritize research needs. From an initial list of 29 evidence gaps, we enumerated 8 high-priority research needs: a) accurate, brief standardized diagnosis and assessment; b) comparative effectiveness and safety of pharmacologic treatments for children under 6 years of age; c) comparative effectiveness of different combinations of psychosocial and pharmacologic treatments for children under 6 years of age; d) case identification and measurement of prevalence and outcomes; e) comparative effectiveness of psychosocial treatment alone versus pharmacologic and combination treatments for children under 6 years of age; f) comparative long-term treatment effectiveness for people 6 years of age and older; g) relative efficacy of specific psychosocial program components for children under 6 years of age; and h) identification of person-level effect modifiers for people 6 years of age and older. In this article, we describe these future research needs in detail and discuss study designs that could be used to address them.

Future research needs for evaluating the integration of mental health and substance abuse treatment with primary care.

Research needs are many in the current health care environment. In this article, we describe a novel method developed by the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center Program for prioritizing areas for future research. Using a recent- ly published systematic review as a foundation, investigators worked with a diverse group of 10 stakeholders to identify and prioritize research needs. We enumerate 13 high-priority research needs, as determined by stakeholders who represented researchers, funders, health care providers, and patients and families, and discuss considerations for specific study designs. Our findings suggest that future research on integrating mental health and primary care should focus first on a) identifying methods of integrating primary care into specialty mental health settings, b) identifying cross-cutting strategies for integration across multiple mental health diagnostic categories as opposed to a separate strategy for each diagnostic category, and c) examining the use of information technology for integrating mental and general medical health care. Other priorities for consideration include examining the economic and organizational sus- tainability of successful integration models, identifying dissemination methods for various settings, examining the business case for integration as well as methods of payment, assessing the cost-effectiveness of integration, and identifying key components of successful strategies. The importance of sustainability and economic justification for integrated care strategies was a recurring theme in discussions with the stake- holders. The ability to sustain integrated care in everyday practice remains to be proved and will depend in part on the level of incentives and sup- port provided through payment system reform, as well as the ability of practices to provide care efficiently.

Interventions to prevent post-traumatic stress disorder: a systematic review.

CONTEXT: Traumatic events are prevalent worldwide; trauma victims seek help in numerous clinical and emergency settings. Using effective interventions to prevent post-traumatic stress disorder (PTSD) is increasingly important. This review assessed the efficacy, comparative effectiveness, and harms of psychological, pharmacologic, and emerging interventions to prevent PTSD. EVIDENCE ACQUISITION: The following sources were searched for research on interventions to be included in the review: MEDLINE; Cochrane Library; CINAHL; EMBASE; PILOTS (Published International Literature on Traumatic Stress); International Pharmaceutical Abstracts; PsycINFO; Web of Science; reference lists of published literature; and unpublished literature (January 1, 1980 to July 30, 2012). Two reviewers independently selected studies, extracted data or checked accuracy, assessed study risk of bias, and graded strength of evidence. All data synthesis occurred between January and September 2012. EVIDENCE SYNTHESIS: Nineteen studies covered various populations, traumas, and interventions. In meta-analyses of three trials (from the same team) for people with acute stress disorder, brief trauma-focused cognitive behavioral therapy was more effective than supportive counseling in reducing the severity of PTSD symptoms (moderate-strength); these two interventions had similar results for incidence of PTSD (low-strength); depression severity (low-strength); and anxiety severity (moderate-strength). PTSD symptom severity after injury decreased more with collaborative care than usual care (single study; low-strength). Debriefing did not reduce incidence or severity of PTSD or psychological symptoms in civilian traumas (low-strength). Evidence about relevant outcomes was unavailable for many interventions or was insufficient owing to methodologic shortcomings. CONCLUSIONS: Evidence is very limited regarding best practices to treat trauma-exposed individuals. Brief cognitive behavioral therapy may reduce PTSD symptom severity in people with acute stress disorder; collaborative care may help decrease symptom severity post-injury.

Cross-site evaluation of a comprehensive pediatric asthma project: the Merck Childhood Asthma Network, Inc. (MCAN).

The Merck Childhood Asthma Network, Inc. (MCAN) initiative selected five sites that had high asthma burden and established asthma programs but were ready for greater program integration across schools, health care systems, and communities. MCAN supported a community-based approach that was tailored to the needs of each program site. As a result, each site was unique in its combination of interventions, but all sites served common goals of integration of care, incorporation of evidence-based programs, and improvement in knowledge, self-management, health, and quality of life. This case study of the MCAN cross-site evaluation discusses the challenges associated with evaluating interventions involving multiple stakeholders that have been adjusted to fit the unique needs of specific communities. The evaluation triangulates data from site-specific monitoring and evaluation data; site documents, site visits, and cross-site meetings; qualitative assessments of families, organizational partners, and other stakeholders; and quantitative data from a common instrument on health indicators before and after the intervention. The evaluation employs the RE-AIM framework--reach, effectiveness, adoption, implementation, and maintenance--to assess the barriers and facilitators of translation from theory into practice. Our experience suggests trade-offs between rigor of evaluation and burden of assessment that have applicability for other community-based translational efforts.

Outcomes from a cross-site evaluation of a comprehensive pediatric asthma initiative incorporating translation of evidence-based interventions.

This article reports on an evaluation of the Merck Childhood Asthma Network, Inc. (MCAN) initiative using pooled cross-site data on patient-reported outcomes pre- and postintervention to quantify the changes experienced by children in five program sites supported by the network. The results show a consistent pattern of improvement across all measured outcomes, including symptoms, hospital and emergency department use, school absences, and caregiver confidence. Children who started with uncontrolled asthma experienced larger improvements than children with controlled asthma at baseline. However, even considering the significant gains made by children with uncontrolled asthma at baseline, after 12 months, most of the outcomes for these children were significantly worse than the 12-month outcomes for children with controlled asthma at baseline. The evaluation of the MCAN initiative offers a model that can be used in cases where resources must be balanced between evaluation and delivering services to children. The design process and results from the common survey instrument provide information for future initiatives seeking to translate evidence-based interventions in a community-based setting.

Balancing "fidelity" and community context in the adaptation of asthma evidence-based interventions in the "real world".

The Merck Childhood Asthma Network (MCAN) initiative selected five sites (New York City, Puerto Rico, Chicago, Los Angeles, and Philadelphia) to engage in translational research to adapt evidence-based interventions (EBIs) to improve childhood asthma outcomes. The authors summarize the sites' experience by describing criteria defining the fidelity of translation, community contextual factors serving as barriers or enablers to fidelity, types of adaptation conducted, and strategies used to balance contextual factors and fidelity in developing a "best fit" for EBIs in the community. A conceptual model captures important structural and process-related factors and helps frame lessons learned. Site implementers and intervention developers reached consensus on qualitative rankings of the levels of fidelity of implementation for each of the EBI core components: low fidelity, adaptation (major vs. minor), or high fidelity. MCAN sites were successful in adapting core EBI components based on their understanding of structural and other contextual barriers and enhancers in their communities. Although the sites varied regarding both the EBI components they implemented and their respective levels of fidelity, all sites observed improvement in asthma outcomes. Our collective experiences of adapting and implementing asthma EBIs highlight many of the factors affecting translation of evidenced-based approaches to chronic disease management in real community settings.

Desired attributes and skills of program managers in translation of evidence-based interventions.

Successful chronic disease project management, especially of multiyear initiatives using evidence-based interventions (EBIs), is of great importance to funders, health care decision makers, and researchers, particularly in light of limited funding. However, a gap in knowledge may exist regarding which attributes and skills are most desirable in a program manager to help him or her ensure successful implementation of EBIs. Although some literature examines the dynamics contributing to the success of community coalitions, public health leadership, and community health education, there is minimal literature exploring the significance of a program manager's role in the conceptualization, implementation, and sustainability of initiatives to improve patient and community health. The authors present their experiences as participants in a large-scale asthma initiative implemented in priority communities, as well as results of a survey distributed among all personnel of the program sites. The survey aimed to assess the key skills and attributes, in addition to contextual factors, that contribute to the strength of a program manager overseeing EBIs in asthma initiatives. The results suggest that certain attributes and skills are desirable in recruiting and hiring of a program manager, especially when augmented by ongoing skill-building training, and can help ensure program and research success.

Translating evidence-based interventions into practice: the design and development of the Merck Childhood Asthma Network, Inc. (MCAN).

Pediatric asthma is a multifactorial disease, requiring complex, interrelated interventions addressing children, families, schools, and communities. The Merck Childhood Asthma Network, Inc. (MCAN) is a nonprofit organization that provides support to translate evidence-based interventions from research to practice. MCAN developed the rationale and vision for the program through a phased approach, including an extensive literature review, stakeholder engagement, and evaluation of funding gaps. The analysis pointed to the need to identify pediatric asthma interventions implemented in urban U.S. settings that have demonstrated efficacy and materials for replication and to translate the interventions into wider practice. In addition to this overall MCAN objective, specific goals included service and system integration through linkages among health care providers, schools, community-based organizations, patients, parents, and other caregivers. MCAN selected sites based on demonstrated ability to implement effective interventions and to address multiple contexts of pediatric asthma prevention and management. Selected MCAN program sites were mature institutions or organizations with significant infrastructure, existing funding, and the ability to provide services without requiring a lengthy planning period. Program sites were located in communities with high asthma morbidity and intended to integrate new elements into existing programs to create comprehensive care approaches.