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Background: Identification of exposures in patients with interstitial lung diseases (ILDs) is essential for diagnosis and management and can be facilitated through the use of exposure questionnaires. However, for most ILDs, a patient-focused questionnaire is lacking. Cognitive interviewing is a methodology used to evaluate sources of understanding and misunderstanding in a questionnaire and to provide evidence of content validity. We developed and refined a new exposure questionnaire for patients with fibrotic ILDs by using cognitive interviewing to establish its understandability and content validity. Methods: An exposure assessment questionnaire was developed by a multidisciplinary team. Cognitive interviews with 24 patients with fibrosing ILDs were conducted by trained interviewers over the phone or Zoom using a semi-structured interview guide. The questionnaire was amended based on the interviewers' interpretation of sources of misunderstanding. The revised questionnaire was tested in a second round of cognitive interviews with a different group of 24 patients. Results: Among the 48 patients who completed interviews, mean age was 61 years, 58.3% were male and 75.0% were white. Based on the first round of cognitive interviews, the multidisciplinary team modified the questions, organization, and instructions of the questionnaire to facilitate recall, adjust for exposures that were frequently misunderstood or required clarification, and focus on clinically relevant exposures. The revised questionnaire performed well in the second round of interviews. Conclusion: An exposure questionnaire, developed with input from patients, can be used to assess clinically relevant exposures in adults with fibrosing ILDs. This is the first questionnaire for all types of fibrosing ILD to have undergone content validation. [ABSTRACT FROM AUTHOR]

Infectious diseases are the leading cause of morbidity and mortality worldwide. Causative pathogenic microbes readily mutate their genome and lead to outbreaks, challenging the healthcare and the medical support. Understanding how certain symptoms manifest clinically is integral for therapeutic decisions and vaccination efficacy/protection. Notably, the interaction between infecting pathogens, host response and co-presence of microbes influence the trajectories of disease progression and clinical outcome. The spectrum of observed symptomatic patients (mild, moderate and severe) and the asymptomatic infections highlight the challenges and the potential for understanding the factors driving protection/susceptibility. With the increasing repertoire of high-throughput tools, such as cutting-edge multi-omics profiling and next-generation sequencing, genetic drivers of factors linked to heterogeneous disease presentations can be investigated in tandem. However, such strategies are not without limits in terms of effectively integrating host–pathogen interactions. Nonetheless, an integrative genomics method (for example, RNA sequencing data) for exploring multiple layers of complexity in host–pathogen interactions could be another way to incorporate findings from high-throughput data. We further propose that a Holo-transcriptome-based technique to capture transcriptionally active microbial units can be used to elucidate functional microbiomes. Thus, we provide holistic perspective on investigative methodologies that can harness the same genomic data to investigate multiple seemingly independent but deeply interconnected functional domains of host–pathogen interaction that modulate disease severity and clinical outcomes. [ABSTRACT FROM AUTHOR]

Frailty, measured as a single construct, is associated variably with poor outcomes before and after lung transplantation. The usefulness of a comprehensive frailty assessment before transplantation is unknown. How are multiple frailty constructs, including phenotypic and cumulative deficit models, muscle mass, exercise tolerance, and social vulnerabilities, measured before transplantation, associated with short-term outcomes after lung transplantation? We conducted a retrospective cohort study of 515 lung recipients who underwent frailty assessments before transplantation, including the short physical performance battery (SPPB), transplant-specific frailty index (FI), 6-min walk distance (6MWD), thoracic sarcopenia, and social vulnerability indexes. We tested the association between frailty measures before transplantation and outcomes after transplantation using logistic regression to model 1-year survival and zero-inflated negative binomial regression to model hospital-free days (HFDs) in the first 90 days after transplantation. Adjustment covariates included age, sex, native lung disease, transplantation type, lung allocation score, BMI, and primary graft dysfunction. Before transplantation, 51.3% of patients were frail by FI (FI ≥ 0.25) and no patients were frail by SPPB. In multivariate adjusted models that also included FI, SPPB, and 6MWD, greater frailty by FI, but not SPPB, was associated with fewer HFDs (–0.006 per 0.01 unit worsening; 95% CI, –0.01 to –0.002 per 0.01 unit worsening) among discharged patients. Greater SPPB deficits were associated with decreased odds of 1-year survival (OR, 0.51 per 1 unit worsening; 95% CI, 0.28-0.93 per 1 unit worsening). Correlation among frailty measurements overall was poor. No association was found between thoracic sarcopenia, 6MWD, or social vulnerability assessments and short-term outcomes after lung transplantation. Both phenotypic and cumulative deficit models measured before transplantation are associated with short-term outcomes after lung transplantation. Cumulative deficit measures of frailty may be more relevant in the first 90 days after transplantation, whereas phenotypic frailty may have a stronger association with 1-year survival. [Display omitted] [ABSTRACT FROM AUTHOR]

Lung transplantation improves survival and quality of life in patients with advanced pulmonary disease. Over the past several decades, the volume of lung transplants has grown substantially, with increasing transplantation of older and acutely ill individuals facilitated by improved utilization and preservation of available donor organs. Other advances include improvements in the diagnosis and mechanistic understanding of frequent post-transplant complications, such as primary graft dysfunction, acute rejection, and chronic lung allograft dysfunction (CLAD). CLAD occurs as a result of the host immune response to the allograft and is the principal factor limiting long-term survival after lung transplantation. Two distinct clinical phenotypes of CLAD have emerged, bronchiolitis obliterans syndrome and restrictive allograft syndrome, and this distinction has enabled further understanding of underlying immune mechanisms. Building on these advances, ongoing studies are exploring novel approaches to diagnose, prevent, and treat CLAD. Such studies are necessary to improve long-term outcomes for lung transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Pulmonary fibrosis (PF) is the most common disease indication for lung transplantation. Our recent work implicated an excess of rare genetic variants in the telomere-related genes TERT, RTEL1, and PARN in PF disease risk. The impact of such variants on posttransplant outcomes is uncertain. The objective of this study was to determine if patients with these PF-associated variants have altered rates of posttransplant acute rejection (AR), chronic lung allograft dysfunction (CLAD), and survival.Methods: The study cohort consisted of 262 PF lung transplant recipients previously genetically characterized by whole exome sequencing. Thirty-one patients (11.8%) had variants in TERT, RTEL1, or PARN, whereas 231 (88.2%) did not. Multivariate Cox proportional hazards models adjusted for relevant clinical variables were used to assess the outcomes of death and CLAD. The AR burden was quantified and compared over the first posttransplant year.Results: Patients with PF with disease-associated variants in TERT, RTEL1, or PARN had a significantly higher risk of death (adjusted hazard ratio [HR], 1.82; 95% CI, 1.07-3.08; P = .03) and CLAD (adjusted HR, 2.88; 95% CI, 1.42-5.87; P = .004) than patients without these variants. There was no difference in AR burden or rates of grade 3 primary graft dysfunction between the two groups.Conclusions: Rare variants in the telomere-related genes TERT, RTEL1, or PARN are associated with poor posttransplant outcomes among PF lung transplant recipients. Further research is needed to understand the biological mechanisms by which telomere-related variants increase the risk for death and CLAD. [ABSTRACT FROM AUTHOR]

Multiple intimate partner violence (IPV) educational programs have been developed for health care professionals (HCPs); however, program content and effectiveness vary substantially. The purpose of this scoping review was to identify and synthesize the literature evaluating IPV education programs for HCPs to identify key areas for potential evidence-based recommendations and focus future research priorities. We conducted a systematic literature search using broad eligibility criteria to identify studies published between January 2000 and July 2015 that evaluated the effectiveness of IPV education programs in health care settings. All potentially eligible references were screened independently by two reviewers. Data extraction was completed independently by two reviewers for all eligible studies. Descriptive statistics were used to summarize all data. We identified 65 eligible studies, 55% of which reported positive program effectiveness. Effective programs often reported the use of online training components, delivery by an IPV educator/expert or physician/surgeon, the inclusion of a treatment protocol and resources for patients and HCPs, and included more than five training sessions lasting no more than one hours each. Our results demonstrate that IPV educational programs are heterogeneous and that a wide variety of methodologies have been used to evaluate their effectiveness. [ABSTRACT FROM AUTHOR]

Mine-risk education programmes will fall short of their intended impact for as long as they fail to take into account local responses--knowledge, logic and everyday practices--to mine threats. Community information, systematically collected through household and institutional surveys, can help to define and understand endogenous 'mine smartness'. The same evidence provides insight into the impact of mine-risk education, including its unintended consequences. Using six criteria of mine smartness, CIET carried out evaluations of mine-risk education in Afghanistan (1997) and Angola (1999). The first clear lesson to be drawn from these evaluations is that people in mine-affected areas do generate their own broadly effective means of facing the daily threat of mines. The second lesson is that people take risks for reasons that make sense to them: 'education' that landmines are dangerous probably adds little value for them. The third lesson is that mine-risk education that does not take into account these first two lessons can cause harm. The evaluations produced evidence of unintended risk-taking by people exposed to mine-risk education programmes. [ABSTRACT FROM AUTHOR]

B METHODS: b We used data from the IPF-PRO Registry, a multicenter, observational registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months, to evaluate PROs at the time of enrollment (June 2014 - July 2018). Funding to coordinate IPF-PRO Registry relationship with Faculty member in DCRI, which receives support from BI Please note: $5001 - $20000 Added 03/14/2019 by Laurie Snyder, source=Web Response, value=Grant/Research Support. [Extracted from the article]

Background: Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients.Methods: This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models adjusted for age. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis.Results: The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (25.9%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.02 and p = 0.03 respectively), and ET-1 predicted future 6MWD (p = 0.02). ET-1 (p = 0.01) and cGMP/NT-proBNP ratio (p = 0.04) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.01) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p = 0.03) and PAH patients on ERA therapy (p = 0.01).Conclusions: ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary arterial hypertension (PAH) carries significant morbidity and mortality. Its diagnosis requires meeting specific hemodynamic and clinical criteria and can be particularly challenging in patients with concomitant heart or lung disease. Hyperpolarized 129Xenon (129Xe) magnetic resonance imaging and dynamic spectroscopy may overcome these challenges, providing a non-invasive new tool to diagnose and monitor PAH. This is based on its unique cardiogenic oscillations reflected in the 129Xe spectrum as it transfers to red blood cells (RBCs, Figure). Hypothesis: We hypothesized that changes in the RBC 129Xe spectroscopic parameters will discriminate PAH from healthy volunteers, patients with left heart failure, idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD). Methods: 129Xe spectra were dynamically acquired every 20 milliseconds in all subjects. At each time point, the amplitude, chemical shift, linewidth, and phase of the 129Xe-RBC resonance was calculated. Cardiogenic oscillations in these spectral parameters were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Wilcoxon rank sum test. Results: A total of 14 healthy volunteers, 10 subjects with PAH, 5 subjects with left heart failure, 9 subjects with IPF, and 7 subjects with COPD underwent 129Xe spectroscopy. In patients with PAH, RBC amplitude oscillations were significantly reduced compared to those with IPF (p < 0.001) or healthy subjects (p = 0.0064, Figure). Oscillations in chemical shift and phase were only observed in IPF patients. Conclusions: 129Xenon dynamic spectroscopy produces different RBC signatures in patients with PAH, IPF, and healthy volunteers. 129Xe uniquely probes the alveolar-capillary interface and can thus detect the effect of arterial lesions on capillary blood volume oscillations. [ABSTRACT FROM AUTHOR]

Pediatric School Outreach (PSO) is a school-based health center (SBHC) in an urban elementary school in Toronto, Canada. PSO focuses on developmental, behavioral, mental health, and educational concerns. A retrospective chart review aimed to characterize demographics, diagnoses, and referrals of patients attending PSO. Of 137 children, ages 2 to 15 years, 73.7% were male; 58.1% had a household annual income of <$30 000 CAD. Possible or confirmed diagnoses included attention deficit hyperactivity disorder (48.5%), learning disability (35.6%), anxiety (22.0%), autism spectrum disorder (16.7%), oppositional defiant disorder (14.4%), and expressive language delay (11.4%). Involvement of community mental health and other agencies was advised in 37.9% of cases. Psychoeducational testing was recommended for 25.0% of patients. Results suggest the need for timely developmental testing, particularly for autism spectrum disorder, and accessible learning disability diagnostic support. There is potential for expansion of interprofessional care at PSO, including psychology, psychiatry, social work, and behavior therapy. [ABSTRACT FROM AUTHOR]

Large cluster of 16 lncRNAs (lnc-STIM2-7:1, lnc-MSH3-2:1, lnc-KCNE1B-3:5, lnc-IRS4-2:1, lnc-PRR32-4:2, lnc-MYO16-7:1, lnc-UTY-17:1, lnc-KCNE1B-155:1, lnc-KCNE1B-3:3, LINC00273:1, lnc-GPR39-10:2, lnc-TMEM132C-11:1, lnc-KCNE1B-3:2, lnc-KCNE1B-3:4, LINC00273:11, LINC00273:13) was obtained downregulated in mortality patients, suggesting possible association of these lncRNAs with COVID-19 mortality. To understand role of lncRNAs in modulating host response in the patients who succumbed to COVID-19, we performed differential expression analysis between recovered and mortality patients. LncRNAs harbouring regulatory motifs within repeat elements modulate immune response towards COVID-19 disease severity and clinical outcomes. [Extracted from the article]

The pink circles represent the upregulated genes, and the cyan circles denote interacting genes of the network gl To understand differential disease severity within recovered, we looked further into the transcriptomic profile between mild, moderate, severe and mortality (Supporting Information S1; Figure 2A). Moderate and severe patients' comparisons with mild revealed a distinct DEG profile, with 17 upregulated and two downregulated genes in moderate, whereas only six upregulated genes in severe compared to mild. Human-host transcriptomic analysis reveals unique early innate immune responses in different sub-phenotypes of COVID-19. [Extracted from the article]

Background: Limited data are available on the association between clinically measured disease severity markers and quality of life (QOL) in idiopathic pulmonary fibrosis (IPF). The study examined the associations between objective disease severity metrics and QOL in a contemporary IPF population.Methods: This study evaluated baseline data from patients enrolled in the multicenter, US-based Idiopathic Pulmonary Fibrosis Prospective Outcomes Registry between June 2014 and July 2018. Disease severity metrics included FVC % predicted, diffusing capacity for carbon monoxide (Dlco) % predicted, supplemental oxygen use with activity, supplemental oxygen use at rest, and two summary scores (the Gender-Age-Lung Physiology index, based on gender, age, and % predicted values for Dlco and FVC; and the Composite Physiologic Index, based on % predicted values for Dlco, FVC, and FEV1). Multivariable adjusted regression models were used to examine cross-sectional associations between each severity measure and St. George's Respiratory Questionnaire (SGRQ) total score.Results: Among 829 patients with complete SGRQ data, the median (interquartile range) SGRQ score at enrollment was 40 (26-53), with higher scores indicating worse QOL. Modest SGRQ impairments were observed with increasing Gender-Age-Lung Physiology score (2.9 [1.8-4.0] per 1-point increase] and with increasing Composite Physiologic Index scores (3.0 [2.4-3.6] per 5-point increase). Substantial SGRQ impairments were observed for oxygen use with activity (15.6 [12.9-18.2]), oxygen use at rest (16.2 [13.0-19.4]), and decreasing Dlco (5.0 [4.0-6.1] per 10% decrease in % predicted).Conclusions: Objective measures of disease severity, including severity scores, physiologic parameters, and supplemental oxygen use, are associated with worse QOL in patients with IPF.Trial Registry: ClinicalTrials.gov; No.: NCT01915511; URL: www.clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

Introduction: Between 38 and 59 percent of women presenting to health care professionals have experienced intimate partner violence. Consequently, multiple intimate partner violence identification or screening programs within health care settings have been developed; however, substantial variations in program content and interpretation of program effectiveness has resulted in conflicting practice guidelines. The purpose of our scoping review is to broadly identify and synthesize the available literature evaluating intimate partner violence identification programs within health care settings to identify key areas for potential evidence-based recommendations and to focus research priorities in the field. Materials and Methods: We conducted a search of MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and psycINFO. We used broad eligibility criteria to identify studies that evaluated intimate partner violence identification programs in health care settings. We completed all screening and data extraction independently and in duplicate. We used descriptive statistics to summarize all data. Results: We identified 59 eligible studies evaluating intimate partner violence identification programs within health care settings. The most commonly reported outcome themes were IPV disclosure (69%, n = 35), number of patients screened (39%, n = 20), HCP opinions towards screening (37%, n = 19), and patient opinions towards screening (29%, n = 15). The majority of studies (36 studies (70.6%)) reported positive program evaluation results. Discussion: The majority of studies reported positive program evaluation results. This may suggest that many different intimate partner violence identification programs are beneficial for identifying victims of abuse, however, it remains unknown as to whether identification programs prevent future episodes of abuse. Additionally, the substantial heterogeneity of the intervention characteristics, study methodology, and outcome measures assessed limits the ability to make clear recommendations as to the optimal method(s) of screening. [ABSTRACT FROM AUTHOR]

The global COVID-19 pandemic continues due to emerging Severe Acute Respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC). Here, we performed comprehensive analysis of in-house sequenced SARS-CoV-2 genome mutations dynamics in the patients infected with the VOCs - Delta and Omicron, within Recovered and Mortality patients. Statistical analysis highlighted significant mutations - T4685A, N4992N, and G5063S in RdRp; T19R in NTD spike; K444N and N532H in RBD spike, associated with Delta mortality. Mutations, T19I in NTD spike, Q493R and N440K in the RBD spike were significantly associated with Omicron mortality. We performed molecular docking for possible effect of significant mutations on the binding of Remdesivir. We found that Remdesivir showed less binding efficacy with the mutant Spike protein of both Delta and Omicron mortality compared to recovered patients. This indicates that mortality associated mutations could have a modulatory effect on drug binding which could be associated with disease outcome. Fig. 1: Summary of the possible functional role of SARS-CoV-2 VOCs, mutations, and drug efficacy; with modulatory role in disease severity and clinical outcome. Distribution of SARS-CoV-2 infected individuals with VOCs - Delta and Omicron and segregation based on their disease outcome into Recovered and Mortality. Genome sequencing reveals the mutation spectrum of both VOCs across the different clinical outcome, and the modulatory potential of mutations vis-à-vis interaction to Remdesivir, a widely used drug during the different waves of COVID-19. [Display omitted] • Mutations of SARS-CoV-2 VOCs – Delta and Omicron, within Recovered and Mortality patients. • Statistical analysis highlighted mutations K444N, N532H, Q493R and N440K in Spike to be associated with mortality patients. • Docking and MD simulation revealed potential of mutations on the drug binding efficacy of Remdesivir. • This may be at the background of sub-optimal drug efficacy in the COVID-19 mortality patients. [ABSTRACT FROM AUTHOR]

Emergence of SARS-CoV-2 VOCs at different time points through COVID-19 pandemic raised concern for increased transmissibility, infectivity and vaccination breakthroughs. 1567 international travellers plus community transmission COVID-19 cases were analysed for mutational profile of VOCS, that led to notable waves in India, namely Alpha, Delta, and Omicron. Spike mutations in Linkage Disequilibrium were investigated for potential impact on structural and functional changes of Spike-ACE2. ORF1ab and spike harboured diverse mutational signatures for each lineage. B.1.617.2 and AY. * demonstrated comparable profile, yet non-clade defining mutations were majorly unique between international vs community samples. Contrarily, Omicron lineages showed substantial overlap in non-clade defining mutations, signifying early phase of transmission and evolution within Indian community. Mutations in LD for Alpha [N501Y, A570D, D1118H, S982A], Delta [P681R, L452R, EFR:156–158 G, D950N, G142D] and Omicron [P681H, D796Y, N764K, N969K, N501Y, S375F] resulted in decreased binding affinity of Spike-ACE2 for Alpha and BA.1 whereas Delta, Omicron and BA.2 demonstrated strong binding. Genomic surveillance tracked spread of VOCs in international travellers' vs community transmission. Behavioural transmission patterns of variants, based on selective advantage incurred by spike mutations, led us to predict sudden takeover of Delta over Alpha and BA.2 over BA.1 in India. [Display omitted] • The mutational landscape of 1567 international travellers and community transmission were characterized across VOCs in India • Mutations in LD for VOCs demonstrated differentially altered binding affinity and electrostatic interactions of Spike-ACE2. • Altered Spike-ACE2 affinity among VOCs predicted sudden takeover of Delta over Alpha and BA.2 over BA.1 in India. [ABSTRACT FROM AUTHOR]

B CONCLUSIONS: b Objective measures of disease severity are associated with worse QOL in contemporary IPF patients, with associations observed for composite severity metrics, physiologic parameters and supplemental oxygen use. B CLINICAL IMPLICATIONS: b IPF patients with more severe disease, particularly those who use supplemental oxygen, experience meaningful deficits in QOL. [Extracted from the article]

Background: The lifetime prevalence of intimate partner violence (IPV) for women presenting to health care settings is estimated to be 38–59%. With the goal of providing help to victims of abuse, numerous IPV assistance programmes have been developed and evaluated across multiple health care settings. Objective: Our scoping review provides an overview of this literature to identify key areas for potential evidence-based recommendations and to focus research priorities. Methods: We conducted a search of MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and psycINFO. We used broad eligibility criteria to identify studies that evaluated the effectiveness of IPV assistance programmes delivered within health care settings. We completed all screening and data extraction independently and in duplicate. We used descriptive statistics to summarize all data. Results: Forty-three studies met all eligibility criteria and were included in our scoping review. Nine categories of assistance programmes were identified: counselling/advocacy, safety assessment/planning, referral, providing IPV resources, home visitation, case management, videos, provider cueing, and system changes. Characteristics of programmes amongst studies frequently reporting positive results included those in which one type of active assistance was used (77.8% of studies reported positive results), a counsellor, community worker, or case manager provided the intervention (83.3% of studies reported positive results), and programmes that were delivered over more than five sessions (100.0% of studies reported positive results). Conclusions: IPV assistance programmes are heterogeneous with regards to the types of assistance they include and how they are delivered and evaluated. This heterogeneity creates challenges in identifying which IPV assistance programmes, and which aspects of these programmes, are effective. However, it appears that many different types of IPV assistance programmes can have positive impacts on women. [ABSTRACT FROM AUTHOR]