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.

Trends in Lung Cancer Incidence and Mortality (1990-2019) in the United States: A Comprehensive Analysis of Gender and State-Level Disparities.

PURPOSE: Lung cancer is the leading cause of cancer-related deaths in the United States. This study aims to analyze lung cancer incidence, mortality, and related statistics from 1990 to 2019, focusing on national- and state-level trends and exploring potential disparities between sexes. METHODS: The Global Burden of Disease database was used to extract tracheal, bronchus, and lung cancer mortality data from 1990 to 2019 for both males and females and across all states of the United States. Age-standardized incidence rates, age-standardized mortality rates, disability-adjusted life years (DALYs), and mortality-to-incidence indices (MIIs) were studied to assess for gender-based, geographic, and temporal disparities. Joinpoint regression analysis was performed to further evaluate trends. RESULTS: The incidence of these cancers in the United States decreased between 1990 and 2019 by 23.35%, with a more significant decline in males (37.73%) than females (1.41%). Similarly, for mortality, a decrease was observed for both sexes combined (26.83%), but much more significantly for males (40.23%) than females (6.01%). The MIIs decreased overall, but there were variations across states. DALYs decreased for both sexes combined, with males experiencing a larger reduction, but an increase was noted in some states for females. CONCLUSION: This analysis reveals diverse trends pertaining to the incidence, mortality, and disability burden associated with lung cancer by sex and states in the United States, emphasizing the need for targeted interventions to reduce disparities. These findings contribute to our understanding of the current landscape of lung cancer and can inform future strategies for prevention, early detection, and management.

MEMO1 Is Required for Ameloblast Maturation and Functional Enamel Formation.

Coordinated mineralization of soft tissue is central to organismal form and function, while dysregulated mineralization underlies several human pathologies. Oral epithelial-derived ameloblasts are polarized, secretory cells responsible for generating enamel, the most mineralized substance in the human body. Defects in ameloblast development result in enamel anomalies, including amelogenesis imperfecta. Identifying proteins critical in ameloblast development can provide insight into specific pathologies associated with enamel-related disorders or, more broadly, mechanisms of mineralization. Previous studies identified a role for MEMO1 in bone mineralization; however, whether MEMO1 functions in the generation of additional mineralized structures remains unknown. Here, we identify a critical role for MEMO1 in enamel mineralization. First, we show that Memo1 is expressed in ameloblasts and, second, that its conditional deletion from ameloblasts results in enamel defects, characterized by a decline in mineral density and tooth integrity. Histology revealed that the mineralization defects in Memo1 mutant ameloblasts correlated with a disruption in ameloblast morphology. Finally, molecular profiling of ameloblasts and their progenitors in Memo1 oral epithelial mutants revealed a disruption to cytoskeletal-associated genes and a reduction in late-stage ameloblast markers, relative to controls. Collectively, our findings integrate MEMO1 into an emerging network of molecules important for ameloblast development and provide a system to further interrogate the relationship of cytoskeletal and amelogenesis-related defects.

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: 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.

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: 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: 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.

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.

Psychiatry NCHD referrals to the local emergency department in the context of an in-house primary care service.

OBJECTIVES: Patients with psychiatric illness are at increased risk of developing non-psychiatric medical illnesses. There have been positive reports regarding the integration of primary care services into mental health facilities. Here, we evaluate the appropriateness of psychiatry non-consultant hospital doctors (NCHD) transfers to the local emergency department (ED) in the context of an in-house primary care service. METHODS: We reviewed the inpatient transfers from St Patrick's University Hospital (SPUH) to the local ED at St James' Hospital (SJH) from 1 January 2016 to 31 December 2017. We used inpatient admission to SJH as our primary marker of an appropriate transfer. RESULTS: 246 inpatients were transferred from SPUH to the SJH ED for medical review in the years 2016 and 2017. 27 (11%) of these were referred to the ED by the primary care service. 51% of those referred were admitted with similar rates of admission for both general practitioner (n = 27, 54% admitted) and NCHD initiated referrals (n = 219, 51% admitted). Acute neurological illness, concern regarding a cardiac illness, and deliberate self-harm were the most common reasons for referral. CONCLUSION: Our primary finding is that, of those transferred to ED by either primary care or a psychiatry NCHD, a similar proportion was judged to be in need of inpatient admission. This indicates that as a group, psychiatry NCHD assessment of acuity and need for transfer was similar to that of their colleagues in primary care.

A psychoeducational intervention increases use of a delirium protocol by Neurologists and Neurosurgeons in patients with brain disorders.

OBJECTIVES: Over 50% of inpatients with neurological disorders may present with a co-morbid psychiatric illness. Delirium has a reported point prevalence of 20% in hospital inpatients and is frequently undetected. We aimed to (1) examine inpatient referrals to a Liaison Neuropsychiatry service and (2) review the diagnosis and management of delirium before and after an educational intervention. METHODS: An initial 6-month audit of referrals to the inpatient Liaison Neuropsychiatry service was conducted in 2018. We then undertook a psychoeducational intervention to raise awareness of the diagnosis and management of delirium. We conducted a re-audit of referrals to the service in 2019. RESULTS: On initial audit, of 84 referrals, the most common referral was for mood (38%; n = 32). Just 4% (n = 3) had a specific delirium query. Following assessment by Neuropsychiatry, organic disorders (43%; n = 32), including delirium (33%; n = 25), were the most common diagnoses. On re-audit, of 86 referrals, mood assessment remained the most common reason for referral (38%; n = 33) and 2% (n = 2) were referred for possible delirium. Organic disorders remained the most common diagnoses (53%; n = 45) including delirium (38%; n = 32). We found a significant increase in the use of the delirium protocol from 12% (n = 3) on initial audit to 47% (n = 15); p < 0.01 on re-audit despite no increase in the number of specific delirium queries. CONCLUSIONS: A psychoeducational intervention improves the management of delirium by Neurologists and Neurosurgeons in patients with brain disorders.

Acculturation and Dental Care-Related Anxiety: An Exploratory Assessment from the Hispanic Community Health Study / Study of Latinos.

This study aimed to determine the associations between acculturation, dental anxiety, and dental utilization among Hispanics/Latinos living in the US. A proxy measure of dental anxiety was available for 7539 adults who had not visited a dentist within the last year. All completed the Short Acculturation Scale for Hispanics (SASH). Bivariate logistic regression and adjusted multivariable logistic regression analysis were conducted. Approximately 22% of the sample was dentally anxious. Dental anxiety was significantly associated with SASH language scale score (OR 1.09, 95%CI 1.02, 1.18, p = 0.04), years in US (OR 1.53, 95%CI 1.23, 1.91, p < 0.0001), and preferred Spanish language (OR 1.30, 95%CI 1.05, 1.63, p = 0.0192); lower acculturation corresponded to higher dental anxiety. Adjusting for sex, age, education, income, insurance, and oral health status, level of acculturation was associated with dental anxiety (AOR 0.87, 95%CI 0.75, 0.91, p = 0.009), but neither were associated with utilization. Acculturation may be an important predictor of dental anxiety for Hispanics/Latinos living in the US.

Care teams misunderstand what most upsets patients about their care.

BACKGROUND: Negative healthcare delivery experiences can cause lasting patient distress and medical service misuse and disuse. Yet no multi-site study has examined whether care-team members understand what most upsets patients about their care. METHODS: We interviewed 373 patients and 360 care-team members in the medical oncology and ambulatory surgery clinics of 11 major healthcare organizations across six U.S. census regions. Patients deeply upset by a service-related experience (n = 99, 27%) answered questions about that experience, while care-team members (n = 360) answered questions about their beliefs regarding what most upsets patients. We performed content analysis to identify memorably upsetting care (MUC) themes; a generalized estimating equation to explore whether MUC theme mention frequencies varied by participant role (care-team member vs. patient), specialty (oncology vs. surgery), facility (academic vs. community), and gender; and logistic regressions to investigate the effects of participant characteristics on individual themes. RESULTS: MUC themes included three systems issues (inefficiencies, access barriers, and facilities problems) and four care-team issues (miscommunication, neglect, coldness, and incompetence). MUC theme frequencies differed by role (all Ps < 0.001), with more patients mentioning care-team coldness (OR = 0.37; 95% CI, 0.23-0.60) and incompetence (OR = 0.17; 95% CI, 0.09-0.31); but more care-team members mentioning system inefficiencies (OR = 7.01; 95% CI, 4.31-11.40) and access barriers (OR, 5.48; 95% CI, 2.81-10.69). CONCLUSIONS: When considering which service experiences most upset patients, care-team members underestimate the impact of their own behaviors and overestimate the impact of systems issues. IMPLICATIONS: Healthcare systems should reconsider how they collect, interpret, disseminate, and respond to patient service reports. LEVEL OF EVIDENCE: Level III.