Treatment of Systemic Sclerosis-associated Interstitial Lung Disease: Evidence-based Recommendations. An Official American Thoracic Society Clinical Practice Guideline.

Background: Interstitial lung disease (ILD) is a significant cause of morbidity and mortality in patients with systemic sclerosis (SSc). To date, clinical practice guidelines regarding treatment for patients with SSc-ILD are primarily consensus based. Methods: An international expert guideline committee composed of 24 individuals with expertise in rheumatology, SSc, pulmonology, ILD, or methodology, and with personal experience with SSc-ILD, discussed systematic reviews of the published evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Predetermined conflict-of-interest management strategies were applied, and recommendations were made for or against specific treatment interventions exclusively by the nonconflicted panelists. The confidence in effect estimates, importance of outcomes studied, balance of desirable and undesirable consequences of treatment, cost, feasibility, acceptability of the intervention, and implications for health equity were all considered in making the recommendations. This was in accordance with the American Thoracic Society guideline development process, which is in compliance with the Institute of Medicine standards for trustworthy guidelines. Results: For treatment of patients with SSc-ILD, the committee: 1) recommends the use of mycophenolate; 2) recommends further research into the safety and efficacy of (a) pirfenidone and (b) the combination of pirfenidone plus mycophenolate; and 3) suggests the use of (a) cyclophosphamide, (b) rituximab, (c) tocilizumab, (d) nintedanib, and (e) the combination of nintedanib plus mycophenolate. Conclusions: The recommendations herein provide an evidence-based clinical practice guideline for the treatment of patients with SSc-ILD and are intended to serve as the basis for informed and shared decision making by clinicians and patients.

Idiopathic pulmonary fibrosis: state of the art for 2023.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease characterised by worsening respiratory symptoms and physiological impairment. Increasing awareness of the clinical manifestations of IPF, more widespread use of computed tomography scans and other potential factors have contributed to a rising prevalence of IPF over the last two decades, especially among people over the age of 65 years. Significant advances in the understanding of the pathobiology of IPF have emerged, and multiple genetic and nongenetic contributors have been identified. The individual patient course and the rate of disease progression in IPF are often unpredictable and heterogeneous. The rate of lung function decline is further modified by treatment with antifibrotic therapies, which have been shown to slow down disease progression. The presence of comorbid conditions may increase symptom burden and impact survival. Clinical monitoring at regular intervals to assess for disease progression by worsening symptoms, physiological parameters and/or radiological features is essential to assess the natural disease course and to guide further management, including prompt detection of complications and comorbid conditions that warrant additional treatment considerations, and timely consideration of referral to palliative care and lung transplantation for the appropriate patient. More studies are needed to determine whether early detection of IPF might improve patient outcomes. The purpose of this concise clinical review is to provide an update on IPF diagnosis, epidemiology, natural history and treatment in the context of new knowledge and latest clinical practice guidelines.

Author Correction: SciPy 1.0: fundamental algorithms for scientific computing in Python.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SciPy 1.0: fundamental algorithms for scientific computing in Python.

SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 9. Key stakeholder perspectives on strengthening the CBIO+ Approach.

BACKGROUND: Community-based health interventions have been an integral part of recent health gains globally. An innovative approach to delivering community health care combines the Census-Based, Impact-Oriented (CBIO) Approach with Care Groups and Community Birthing Centers called Casas Maternas Rurales. CBIO+ was adopted by Curamericas/Guatemala in its Maternal and Child Health Project, 2011-2015. Here, we describe the opinions of Project staff and local government health care workers about the strengths and challenges of CBIO+.  METHODS: Self-administered questionnaires, key informant interviews, and focus group discussions were used to obtain the views of 21 staff members from Curamericas/Guatemala as well as 15 local government health workers. The evaluation focused on four primary areas: (1) advisability of integrating the CBIO+ Approach into the government's rural health system, (2) staff knowledge of the CBIO+ Approach, (3) advantages, disadvantages and challenges of the CBIO+ Approach, and (4) proposed improvements to the CBIO+ Approach. The data were coded into categories and from these categories themes were derived. RESULTS: The most commonly mentioned advantage of CBIO+ was the inclusion of the community in program planning, which improved participation. Many respondents noted that the CBIO+ Approach was challenging to implement in communities with internal conflicts. Among other challenges mentioned were coordinating (both among the Project staff and with others in the communities), maintenance of a high level of community participation, and overcoming opposition of men to women's participation in Care Groups. The staff mentioned a number of possible changes, including increasing male involvement, raising salaries for community-level paid staff, providing volunteers with incentives, and improving coordination both internally and externally. There was a strong demand among the local Ministry of Public Health and Social Welfare staff for the Project to continue. CONCLUSION: The CBIO+ Approach and its implementation by Curamericas/Guatemala was overall embraced by local staff. By eliciting feedback while the project was ongoing, actionable areas for improvement were identified.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 3. Expansion of population coverage of key interventions.

BACKGROUND: This is the third in a series of 10 articles describing the Curamericas/Guatemala Maternal and Child Health Project, 2011-2015, and its effectiveness in improving the health and well-being of 15,327 children younger than 5 years of age and 32,330 women of reproductive age in the Department of Huehuetenango in180 communities that make up the municipalities of San Sebastian Coatán, Santa Eulalia, and San Miguel Acatán. The Project combined the Census-Based, Impact-Oriented (CBIO) Approach with the Care Group Approach and the  Community Birthing Center (Casa Materna Rural) Approach. This combined approach we refer to as CBIO+. The Project trained women volunteers every two weeks (in Care Groups) to provide health education to neighboring households. Messages focused on the promotion of maternal and newborn health, nutrition, prevention and treatment of acute respiratory infection and diarrhea in children, and immunizations. METHODS: Household knowledge, practice and coverage (KPC) surveys were executed at baseline in January 2011 and at endline in June 2015 to measure changes in levels of knowledge of danger signs, key household practices (such as Essential Newborn Care and handwashing), and health service utilization (such as antenatal care and care seeking for a child with signs of pneumonia) in two separate Project Areas (Area A with 41 months and Area B with 20 months of full intervention implementation). RESULTS: For the 24 indicators of the interventions under the Project's control, statistically significant improvements were observed for 21 in Area A and 19 in Area B. However, for some of the interventions that required support from the government's Extension of Coverage Program (immunization, family planning, and vitamin A administration) no improvements were noted because of the cessation of the program by the government after Project implementation began. In both Areas A and B one-half of the indicators improved by at least two-fold. CONCLUSION: This community-based Project has been effective in quickly achieving marked improvements in indicators for interventions that are important for the health of mothers and children. These achievements are notable in view of the challenging context in which the Project was implemented.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 4. Nutrition-related activities and changes in childhood stunting, wasting, and underweight.

BACKGROUND: This is the fourth paper in our supplement on improving the health and well-being of rural indigenous Maya mothers and children in the Western Highlands of Guatemala, where the prevalence of stunting is the highest in Latin America and among the highest in the world. Reducing childhood undernutrition was one of the objectives of the Maternal and Child Health Project, 2011-2015, implemented by Curamericas/Guatemala. The implementation research portion of the Project attempted to determine if there were greater improvements in childhood nutritional status in the Project Area than in comparison areas and whether or not a dose-response effect was present in terms of a greater improvement in the Project Area with a longer duration of interventions.  METHODS: The Project provided nutrition-related messages to mothers of young children, cooking sessions using locally available nutritious foods, a lipid-based nutrient supplement (Nutributter®) for a short period of time (4 months), anti-helminthic medication, and repeated growth monitoring and nutrition counseling. Measures of height and weight for calculating the prevalence of underweight, stunting, and wasting in under-2 children were analyzed and compared with the anthropometric data for children in the rural areas of the Northwestern Region and in the Western Highlands of Guatemala. RESULTS: The prevalence of stunting declined in Area A from 74.5% in September 2012 to 39.5% in June 2015. Area A comprised approximately one-half of the Project Area and was the geographic area with the greatest intensity and duration of nutrition-related Project interventions. Minimal improvements in stunting were observed in the Northwestern Region, which served as a comparison area. Improvements in multiple output and outcome indicators associated with nutritional status were also observed in Areas A and B: infant and young child feeding practices, routine growth monitoring and counseling, and household practices for the prevention and treatment of diarrhea. CONCLUSION: The Project Area in which Curamericas/Guatemala implemented the CBIO+ Approach experienced a reduction in the prevalence of stunting and other measures of undernutrition in under-2 children. Given the burden of undernutrition in Guatemala and other parts of the world, this approach merits broader application and further evaluation.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 5. Mortality assessment.

BACKGROUND: The Curamericas/Guatemala Maternal and Child Health Project, 2011-2015, implemented the Census-Based, Impact-Oriented Approach, the Care Group Approach, and the Community Birthing Center Approach. Together, this expanded set of approaches is known as CBIO+. This is the fifth of 10 papers in our supplement describing the Project and the effectiveness of the CBIO+ Approach. This paper assesses causes, levels, and risk factors for mortality along with changes in mortality. METHODS: The Project maintained Vital Events Registers and conducted verbal autopsies for all deaths of women of reproductive age and under-5 children. Mortality rates and causes of death were derived from these data. To increase the robustness of our findings, we also indirectly estimated mortality decline using the Lives Saved Tool (LiST). FINDINGS: The leading causes of maternal and under-5 mortality were postpartum hemorrhage and pneumonia, respectively. Home births were associated with an eight-fold increased risk of both maternal (p = 0.01) and neonatal (p = 0.00) mortality. The analysis of vital events data indicated that maternal mortality declined from 632 deaths per 100,000 live births in Years 1 and 2 to 257 deaths per 100,000 live birth in Years 3 and 4, a decline of 59.1%. The vital events data revealed no observable decline in neonatal or under-5 mortality. However, the 12-59-month mortality rate declined from 9 deaths per 1000 live births in the first three years of the Project to 2 deaths per 1000 live births in the final year. The LiST model estimated a net decline of 12, 5, and 22% for maternal, neonatal and under-5 mortality, respectively. CONCLUSION: The baseline maternal mortality ratio is one of the highest in the Western hemisphere. There is strong evidence of a decline in maternal mortality in the Project Area. The evidence of a decline in neonatal and under-5 mortality is less robust. Childhood pneumonia and neonatal conditions were the leading causes of under-5 mortality. Expanding access to evidence-based community-based interventions for (1) prevention of postpartum hemorrhage, (2) home-based neonatal care, and (3) management of childhood pneumonia could help further reduce mortality in the Project Area and in similar areas of Guatemala and beyond.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ Approach of Curamericas: 1. Introduction and project description.

BACKGROUND: The Curamericas/Guatemala Maternal and Child Health Project, 2011-2015, was implemented in the Western Highlands of the Department of Huehuetenango, Guatemala. The Project utilized three participatory approaches in tandem: the Census-Based, Impact-Oriented (CBIO) Approach, the Care Group Approach, and the Community Birthing Center Approach. Together, these are referred to as the Expanded CBIO Approach (or CBIO+). OBJECTIVE: This is the first article of a supplement that assesses the effectiveness of the Project's community-based service delivery platform that was integrated into the Guatemalan government's rural health care system and its special program for mothers and children called PEC (Programa de Extensión de Cobertura, or Extension of Coverage Program). METHODS: We review and summarize the CBIO+ Approach and its development. We also describe the Project Area, the structure and implementation of the Project, and its context. RESULTS: The CBIO+ Approach is the product of four decades of field work. The Project reached a population of 98,000 people, covering the entire municipalities of San Sebastián Coatán, Santa Eulalia, and San Miguel Acatán. After mapping all households in each community and registering all household members, the Project established 184 Care Groups, which were composed of 5-12 Care Group Volunteers who were each responsible for 10-15 households. Paid Care Group Promoters provided training in behavior change communication every two weeks to the Care Groups. Care Group Volunteers in turn passed this communication to the mothers in their assigned households and also reported back to the Care Group Promoters information about any births or ï»¿deaths that they learned of during the previous two weeks as a result of their regular contact with their neighbors. At the outset of the Project, there was one Birthing Center in the Project Area, serving a small group of communities nearby. Two additional Birthing Centers began functioning as the Project was operating. The Birthing Centers encouraged the participation of traditional midwives (called comadronas) in the Project Area. CONCLUSION: This article serves as an introduction to an assessment of the CBIO+ community-based, participatory approach as it was implemented by Curamericas/Guatemala in the Western Highlands of the Department of Huehuetenango, Guatemala. This article is the first of a series of articles in a supplement entitled Reducing Inequities in Maternal and Child Health in Rural Guatemala through the CBIO+ Approach of Curamericas.

Reducing inequities in maternal and child health in rural Guatemala through the CBIO+ approach of Curamericas: 2. Study site, design, and methods.

BACKGROUND: The Curamericas/Guatemala Maternal and Child Health Project, 2011-2015, included implementation research designed to assess the effectiveness of an approach referred to as CBIO+ , composed of: (1) the Census-Based, Impact-Oriented (CBIO) Approach, (2) the Care Group Approach, and (3) the Community Birthing Center Approach. This is the second paper in a supplement of 10 articles describing the implementation research and its findings. Paper 1 describes CBIO+ , the Project Area, and how the Project was implemented. OBJECTIVE: This paper describes the implementation research design and details of how it was carried out. METHODS: We reviewed the original implementation research protocol and the methods used for all data collection related to this Project. The protocol and methods used for the implementation research related to this Project were all standard approaches to the monitoring and evaluation of child survival projects as developed by the United States Agency for International Development Child Survival and Health Grants Program (CSHGP) and the CORE Group. They underwent independent peer review supervised by the CSHGP before the implementation research began. RESULTS: The study area was divided into two sets of communities with a total population of 98,000 people. Project interventions were implemented in Area A from 2011 until the end of the project in 2015 (44 months) and in Area B from late 2013 until 2015 (20 months). Thus, Area B served as a quasi-comparison area during the first two years of Project implementation. The overarching study question was whether the CBIO+ Approach improved the health and well-being of children and mothers. The outcome indicators included (1) changes in population coverage of evidence-based interventions, (2) changes in childhood nutritional status, (3) changes in the mortality of children and mothers, (4) quality of care provided at Community Birthing Centers, (5) the impact of the Project on women's empowerment and social capital, (6) stakeholder assessment of the effectiveness of the CBIO+ Approach, and (7) the potential of wider adoption of the CBIO+ Approach. CONCLUSION: The implementation research protocol guided the assessment of the effectiveness of the CBIO+ Approach in improving the health and well-being of children, mothers, and their communities.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Airway management guidance for the endemic phase of COVID-19.

It is now apparent that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) will remain endemic for some time. Improved therapeutics and a vaccine may shorten this period, but both are far from certain. Plans must be put in place on the assumption that the virus and its disease will continue to affect the care of patients and the safety of staff. This will impact particularly on airway management due to the inherent risk to staff during such procedures. Research is needed to clarify the nature and risk of respiratory aerosol-generating procedures. Improved knowledge of the dynamics of SARS-CoV-2 infection and immunity is also required. In the meantime, we describe the current status of airway management during the endemic phase of the COVID-19 pandemic. Some controversies remain unresolved, but the safety of patients and staff remains paramount. Current evidence does not support or necessitate dramatic changes to choices for anaesthetic airway management. Theatre efficiency and training issues are a challenge that must be addressed, and new information may enable this.

Granular measures of agricultural land use influence lake nitrogen and phosphorus differently at macroscales.

Agricultural land use is typically associated with high stream nutrient concentrations and increased nutrient loading to lakes. For lakes, evidence for these associations mostly comes from studies on individual lakes or watersheds that relate concentrations of nitrogen (N) or phosphorus (P) to aggregate measures of agricultural land use, such as the proportion of land used for agriculture in a lake's watershed. However, at macroscales (i.e., in hundreds to thousands of lakes across large spatial extents), there is high variability around such relationships and it is unclear whether considering more granular (or detailed) agricultural data, such as fertilizer application, planting of specific crops, or the extent of near-stream cropping, would improve prediction and inform understanding of lake nutrient drivers. Furthermore, it is unclear whether lake N and P would have different relationships to such measures and whether these relationships would vary by region, since regional variation has been observed in prior studies using aggregate measures of agriculture. To address these knowledge gaps, we examined relationships between granular measures of agricultural activity and lake total phosphorus (TP) and total nitrogen (TN) concentrations in 928 lakes and their watersheds in the Northeastern and Midwest U.S. using a Bayesian hierarchical modeling approach. We found that both lake TN and TP concentrations were related to these measures of agriculture, especially near-stream agriculture. The relationships between measures of agriculture and lake TN concentrations were more regionally variable than those for TP. Conversely, TP concentrations were more strongly related to lake-specific measures like depth and watershed hydrology relative to TN. Our finding that lake TN and TP concentrations have different relationships with granular measures of agricultural activity has implications for the design of effective and efficient policy approaches to maintain and improve water quality.

Quantitative Pectoralis Muscle Area is Associated with the Development of Lung Cancer in a Large Lung Cancer Screening Cohort.

BACKGROUND: Studies have demonstrated an inverse relationship between body mass index (BMI) and the risk of developing lung cancer. We conducted a retrospective cohort study evaluating baseline quantitative computed tomography (CT) measurements of body composition, specifically muscle and fat area in a large CT lung screening cohort (CTLS). We hypothesized that quantitative measurements of baseline body composition may aid in risk stratification for lung cancer. METHODS: Patients who underwent baseline CTLS between January 1st, 2012 and September 30th, 2014 and who had an in-network primary care physician were included. All patients met NCCN Guidelines eligibility criteria for CTLS. Quantitative measurements of pectoralis muscle area (PMA) and subcutaneous fat area (SFA) were performed on a single axial slice of the CT above the aortic arch with the Chest Imaging Platform Workstation software. Cox multivariable proportional hazards model for cancer was adjusted for variables with a univariate p < 0.2. Data were dichotomized by sex and then combined to account for baseline differences between sexes. RESULTS: One thousand six hundred and ninety six patients were included in this study. A total of 79 (4.7%) patients developed lung cancer. There was an association between the 25th percentile of PMA and the development of lung cancer [HR 1.71 (1.07, 2.75), p < 0.025] after adjusting for age, BMI, qualitative emphysema, qualitative coronary artery calcification, and baseline Lung-RADS® score. CONCLUSIONS: Quantitative assessment of PMA on baseline CTLS was associated with the development of lung cancer. Quantitative PMA has the potential to be incorporated as a variable in future lung cancer risk models.

Genome-wide association study identifies a novel locus for cannabis dependence.

Despite moderate heritability, only one study has identified genome-wide significant loci for cannabis-related phenotypes. We conducted meta-analyses of genome-wide association study data on 2080 cannabis-dependent cases and 6435 cannabis-exposed controls of European descent. A cluster of correlated single-nucleotide polymorphisms (SNPs) in a novel region on chromosome 10 was genome-wide significant (lowest P=1.3E-8). Among the SNPs, rs1409568 showed enrichment for H3K4me1 and H3K427ac marks, suggesting its role as an enhancer in addiction-relevant brain regions, such as the dorsolateral prefrontal cortex and the angular and cingulate gyri. This SNP is also predicted to modify binding scores for several transcription factors. We found modest evidence for replication for rs1409568 in an independent cohort of African American (896 cases and 1591 controls; P=0.03) but not European American (EA; 781 cases and 1905 controls) participants. The combined meta-analysis (3757 cases and 9931 controls) indicated trend-level significance for rs1409568 (P=2.85E-7). No genome-wide significant loci emerged for cannabis dependence criterion count (n=8050). There was also evidence that the minor allele of rs1409568 was associated with a 2.1% increase in right hippocampal volume in an independent sample of 430 EA college students (fwe-P=0.008). The identification and characterization of genome-wide significant loci for cannabis dependence is among the first steps toward understanding the biological contributions to the etiology of this psychiatric disorder, which appears to be rising in some developed nations.

Electrophilic nitro-fatty acids suppress allergic contact dermatitis in mice.

BACKGROUND: Reactions between nitric oxide (NO), nitrite (NO2-), and unsaturated fatty acids give rise to electrophilic nitro-fatty acids (NO2 -FAs), such as nitro oleic acid (OA-NO2 ) and nitro linoleic acid (LNO2 ). Endogenous electrophilic fatty acids (EFAs) mediate anti-inflammatory responses by modulating metabolic and inflammatory signal transduction reactions. Hence, there is considerable interest in employing NO2 -FAs and other EFAs for the prevention and treatment of inflammatory disorders. Thus, we sought to determine whether OA-NO2 , an exemplary nitro-fatty acid, has the capacity to inhibit cutaneous inflammation. METHODS: We evaluated the effect of OA-NO2 on allergic contact dermatitis (ACD) using an established model of contact hypersensitivity in C57Bl/6 mice utilizing 2,4-dinitrofluorobenzene as the hapten. RESULTS: We found that subcutaneous (SC) OA-NO2 injections administered 18 h prior to sensitization and elicitation suppresses ACD in both preventative and therapeutic models. In vivo SC OA-NO2 significantly inhibits pathways that lead to inflammatory cell infiltration and the production of inflammatory cytokines in the skin. Moreover, OA-NO2 is capable of enhancing regulatory T-cell activity. Thus, OA-NO2 treatment results in anti-inflammatory effects capable of inhibiting ACD by inducing immunosuppressive responses. CONCLUSION: Overall, these results support the development of OA-NO2 as a promising therapeutic for ACD and provides new insights into the role of electrophilic fatty acids in the control of cutaneous immune responses potentially relevant to a broad range of allergic and inflammatory skin diseases.

Evidence of CNIH3 involvement in opioid dependence.

Opioid dependence, a severe addictive disorder and major societal problem, has been demonstrated to be moderately heritable. We conducted a genome-wide association study in Comorbidity and Trauma Study data comparing opioid-dependent daily injectors (N=1167) with opioid misusers who never progressed to daily injection (N=161). The strongest associations, observed for CNIH3 single-nucleotide polymorphisms (SNPs), were confirmed in two independent samples, the Yale-Penn genetic studies of opioid, cocaine and alcohol dependence and the Study of Addiction: Genetics and Environment, which both contain non-dependent opioid misusers and opioid-dependent individuals. Meta-analyses found five genome-wide significant CNIH3 SNPs. The A allele of rs10799590, the most highly associated SNP, was robustly protective (P=4.30E-9; odds ratio 0.64 (95% confidence interval 0.55-0.74)). Epigenetic annotation predicts that this SNP is functional in fetal brain. Neuroimaging data from the Duke Neurogenetics Study (N=312) provide evidence of this SNP's in vivo functionality; rs10799590 A allele carriers displayed significantly greater right amygdala habituation to threat-related facial expressions, a phenotype associated with resilience to psychopathology. Computational genetic analyses of physical dependence on morphine across 23 mouse strains yielded significant correlations for haplotypes in CNIH3 and functionally related genes. These convergent findings support CNIH3 involvement in the pathophysiology of opioid dependence, complementing prior studies implicating the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate system.

An Official American Thoracic Society Research Statement: Implementation Science in Pulmonary, Critical Care, and Sleep Medicine.

BACKGROUND: Many advances in health care fail to reach patients. Implementation science is the study of novel approaches to mitigate this evidence-to-practice gap. METHODS: The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement on implementation science in pulmonary, critical care, and sleep medicine. The committee used an iterative consensus process to define implementation science and review the use of conceptual frameworks to guide implementation science for the pulmonary, critical care, and sleep community and to explore how professional medical societies such as the ATS can promote implementation science. RESULTS: The committee defined implementation science as the study of the mechanisms by which effective health care interventions are either adopted or not adopted in clinical and community settings. The committee also distinguished implementation science from the act of implementation. Ideally, implementation science should include early and continuous stakeholder involvement and the use of conceptual frameworks (i.e., models to systematize the conduct of studies and standardize the communication of findings). Multiple conceptual frameworks are available, and we suggest the selection of one or more frameworks on the basis of the specific research question and setting. Professional medical societies such as the ATS can have an important role in promoting implementation science. Recommendations for professional societies to consider include: unifying implementation science activities through a single organizational structure, linking front-line clinicians with implementation scientists, seeking collaborations to prioritize and conduct implementation science studies, supporting implementation science projects through funding opportunities, working with research funding bodies to set the research agenda in the field, collaborating with external bodies responsible for health care delivery, disseminating results of implementation science through scientific journals and conferences, and teaching the next generation about implementation science through courses and other media. CONCLUSIONS: Implementation science plays an increasingly important role in health care. Through support of implementation science, the ATS and other professional medical societies can work with other stakeholders to lead this effort.