Perception of burden of oral and inhaled corticosteroid adverse effects on asthma-specific quality of life.

BACKGROUND: A multistakeholder core outcome set created for asthma trials showed that asthma-specific quality of life (QoL) was a critically meaningful outcome. However, the definition and measurement methods were undetermined. The adverse effects (AEs) of corticosteroids may be a vital clinical trial outcome. Nevertheless, the AE burden from the patient perspective has not yet been elucidated in an asthma population. OBJECTIVE: To characterize patient burden of AEs in oral (OCS) and inhaled corticosteroids (ICS) and how this relates to QoL within an asthma population. METHODS: We used a convergent parallel mixed-methods design with quantitative surveys of known ICS and OCS AEs that were distributed through the Allergy & Asthma Network database, social channels, and the Asthma UK newsletter. Participants rated the AEs that were (1) most burdensome and (2) most desired to be eliminated. Qualitative interviews and focus groups were performed to better understand patient views on barriers reported in the quantitative data, and to identify patient-important barriers that were not a part of the quantitative survey. RESULTS: The 3 most burdensome AEs for OCS were bone mineral density, infectious complications, and weight gain, whereas weight gain was the most desired to be eliminated. The 3 most burdensome AEs for ICS were pneumonia, hoarse voice, and oral thrush, with concordant results for the most desired to be eliminated. In the focus groups, OCS AEs were concordant with quantitative findings. Focus groups identified unmeasured psychosocial effects, such as embarrassment. CONCLUSION: The most burdensome AEs may not be those that would cause patients to stop therapy. Furthermore, qualitative focus groups suggest a psychosocial burden associated with ICS, which needs further investigation.

Income and Other Contributors to Poor Outcomes in U.S. Patients with Sarcoidosis.

Rationale: Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated.Objectives: To determine the association between income and sarcoidosis outcomes after controlling for socioeconomic and disease-related factors.Methods: Using the Sarcoidosis Advanced Registry for Cures database, we analyzed data from 2,318 patients with sarcoidosis in the United States to determine the effect of income and other variables on outcomes. We divided comorbidities arising after diagnosis into those likely related to steroid use and those likely related to sarcoidosis. We assessed the development of health-related, functional, and socioeconomic outcomes following the diagnosis of sarcoidosis.Measurements and Main Results: In multivariate analysis, low-income patients had significantly higher rates of new sarcoidosis-related comorbidities (<$35,000, odds ratio [OR], 2.4 [1.7-3.3]; $35,000-84,999, OR, 1.4 [1.1-1.9]; and ≥$85,000 [reference (Ref)]) and new steroid-related comorbidities (<$35,000, OR, 1.3 [0.9-2.0]; $35,000-84,999, OR, 1.5 [1.1-2.1]; and ≥$85,000 [Ref]), had lower health-related quality of life as assessed by the Sarcoidosis Health Questionnaire (P < 0.001), and experienced more impact on family finances (<$35,000, OR, 7.9 [4.9-12.7]; $35,000-84,999, OR, 2.7 [1.9-3.9]; and ≥$85,000 [Ref]). The use of supplemental oxygen, need for assistive devices, and job loss were more common in lower income patients. Development of comorbidities after diagnosis of sarcoidosis occurred in 63% of patients and were strong independent predictors of poor outcomes. In random forest modeling, income was consistently a leading predictor of outcome.Conclusions: These results suggest the burden from sarcoidosis preferentially impacts the economically disadvantaged.

Comparison of organ involvement clusters in Black and White American sarcoidosis patients from a prospectively collected patient registry.

BACKGROUND: Due to the heterogeneity of sarcoidosis, there is a need to define clinical phenotypes to allow for tailoring of clinical care and identification of more homogenous populations to facilitate research. METHODS: We utilized data from a prospectively collected registry of sarcoidosis patients seen at a single quaternary referral center between January 2019 and February 2021. We used multiple correspondence analysis (MCA) and k-means clustering to investigate if the clusters previously identified in the GenPhenReSa study were reproducible in a US population. We also investigated if these clusters were stable when the population was stratified by race. RESULTS: We replicated 3 of the 5 clusters seen in the GenPhenReSa study in our cohort. We likewise identified similar clusters between White and Black patients with sarcoidosis. Differences in organ manifestations associations between White and Black patients were seen primarily in relation to cardiac, neurologic, and ocular involvement. CONCLUSIONS: The organ clusters of liver-spleen, isolated pulmonary, and musculoskeletal-skin were reproducible in a US cohort, and in both Black and White patients.

Cardiac Sarcoidosis.

Cardiac involvement is a major cause of morbidity and mortality in patients with sarcoidosis. It is important to distinguish between clinical manifest diseases from clinically silent diseases. Advanced cardiac imaging studies are crucial in the diagnostic pathway. In suspected isolated cardiac sarcoidosis, it's key to rule out alternative diagnoses. Therapeutic options can be divided into immunosuppressive agents, guideline-directed medical therapy, antiarrhythmic medications, device/ablation therapy, and heart transplantation.

Partnering With Patients With Sarcoidosis to Implement a Community Advisory Board.

BACKGROUND: Community advisory boards (CABs) are increasingly recognized as a means of incorporating patient experience into clinical practice and research. The power of CABs is derived from engaging with community members as equals throughout the research process. Despite this, little is known of community member experience and views on best practices for running a CAB in a rare pulmonary disease. RESEARCH QUESTION: What are CAB members' views on the best practices for CAB formation and maintenance in a rare pulmonary disease? STUDY DESIGN AND METHODS: In August 2021, we formed the Cleveland Clinic Sarcoidosis Health Partners (CC-HP) as a CAB to direct research and clinic improvement initiatives at a quaternary sarcoidosis center. We collaboratively evaluated our process for formation and maintenance of the CC-HP with the patient members of the group. Through the series of reflection/debriefing discussions, CAB patient members developed a consensus account of salient obstacles and facilitators of forming and maintaining a CAB in a rare pulmonary disease. RESULTS: Clinician and community members of the CC-HP found published guidelines to be an effective tool for structuring formation of a CAB in a rare pulmonary disease. Facilitators included a dedicated coordinator, collaborative development of projects, and a focus on improving clinical care. Obstacles to CAB functioning were formal structure, focus on projects with academic merit but no immediate impact to patients, and overreliance on digital resources. INTERPRETATION: By centering our evaluation of our CAB on community member experience, we were able to both identify facilitators and impediments to CAB as well as improve our own processes.

Emergency physicians' knowledge of the total charges of medical care.

STUDY OBJECTIVES: This study aimed to evaluate emergency medical physician's knowledge of the charges for the entirety of medical care provided to patients they treated and discharged from the emergency department (ED). METHODS: The study was administered in an academic ED. Patients were eligible for the study if they were discharged from the ED by the attending who first evaluated them. Following patient discharge from the ED, the attending physician and resident were asked to estimate the total billed to the patient (all charges billed to patient before adjustments for insurance provider or coverage status were applied). The median error of the physician's estimate was compared to their years of experience. RESULTS: Physicians underestimated actual total charges 93% (127/136) of the time. The median estimate was 36% (IQR 23%-54%) of the actual final ED charge, representing a median underestimation of $1268 (IQR $766-$2347). There was no correlation between degree of error and postgraduate years of the physician. CONCLUSION: This study demonstrated a significant underestimation of a patient's total charges by emergency medical physicians. There was no correlation in years of experience and ability to accurately estimate charges. While all physicians tended to underestimate charges, physicians tended to have good inter-rater agreement.

Health Disparities: Interventions for Pulmonary Disease - A Narrative Review.

There is expansive literature documenting the presence of health disparities, but there are disproportionately few studies describing interventions to reduce disparity. In this narrative review, we categorize interventions to reduce health disparity in pulmonary disease within the US health care system to support future initiatives to reduce disparity. We identified 211 articles describing interventions to reduce disparity in pulmonary disease related to race, income, or sex. We grouped the studies into the following four categories: biologic, educational, behavioral, and structural. We identified the following five main themes: (1) there were few interventional trials compared with the breadth of studies describing health disparities, and trials involving patients with asthma who were Black, low income, and living in an urban setting were overrepresented; (2) race or socioeconomic status was not an effective marker of individual pharmacologic treatment response; (3) telehealth enabled scaling of care, but more work is needed to understand how to leverage telehealth to improve outcomes in marginalized communities; (4) future interventions must explicitly target societal drivers of disparity, rather than focusing on individual behavior alone; and (5) individual interventions will only be maximally effective when specifically tailored to local needs. Much work has been done to catalog health disparities in pulmonary disease. Notable gaps in the identified literature include few interventional trials, the need for research in diseases outside of asthma, the need for high quality effectiveness trials, and an understanding of how to implement proven interventions balancing fidelity to the original protocol and the need to adapt to local barriers to care.

Barriers to Care among Patients with Sarcoidosis: A Qualitative Study.

Rationale: Lower-income patients with sarcoidosis experience worse outcomes than those with higher incomes. The reasons for these disparities are not well understood. Objectives: To identify patient-reported barriers to and facilitators of self-empowered care among patients with sarcoidosis residing in high- and low-median-income zip-code areas. Methods: Patients with biopsy-proven sarcoidosis who had received pharmacologic treatment within the past year and who were cared for in a sarcoidosis clinic of a large, urban medical system were included. Focus groups were stratified by high- and low-median-income zip-code areas. Transcriptions were analyzed using grounded theory. Results: Five focus groups were created; two included patients living in zip-code areas with high median incomes ($84,263; interquartile range [IQR], $79,334-$89,795), and three included patients living in zip-code areas with low median incomes ($27,470; IQR, $22,412-27,597). Patients with sarcoidosis from low-income and high-income zip-code areas reported remarkably similar experiences. Patients reported that sarcoidosis was a burden owing to its disease manifestations and the adverse effects of treatment, which led to a compromised ability to perform their activities of daily living at home or at work. Reported barriers to care included perceived inadequate knowledge about sarcoidosis among providers, communication barriers with providers, and the high cost of treatment. Patients from low-income zip-code areas experienced discrimination related to race and income, which served to compound their mistrust. Patients sought to overcome these barriers through self-empowerment, including independent learning, self-advocacy, medication nonadherence, and use of alternative therapies. Conclusions: Patients with sarcoidosis who lived in high- and low-income zip-code areas expressed similar overall concerns regarding sarcoidosis care. However, patients from low-income zip-code areas more frequently expressed concerns about racial and income-based discrimination. Patients from both groups addressed these barriers through self-empowerment, which included not adhering to prescribed therapies. Future work should focus on the effects of culturally and socioeconomically congruent, community-engaged interventions for quality of life of patients with sarcoidosis.

Infliximab for Refractory Cardiac Sarcoidosis.

Cardiac sarcoidosis (CS) is frequently difficult to treat. Infliximab (IFX) is useful for extracardiac sarcoidosis, but its use in CS has been limited due to concerns about cardiotoxicity and an FDA blackbox warning about use in heart failure. We reviewed 36 consecutive patients treated with infliximab for CS refractory to standard therapies. IFX was initiated for patients with refractory dysrhythmias, moderate to severe cardiomyopathy, and evidence of persistent F-18 fluorodeoxyglucose uptake on positron emission tomography scan, despite standard therapies. We compared the prednisone dose, ejection fraction (EF), and dysrhythmias before and after IFX therapy. The prednisone-equivalent steroid dose decreased from a median of 20 mg at initiation of infliximab to 7.5 at 6 months and 5 mg at 12 months postinitiation of infliximab (p <0.001). In the 25 patients with serial EF measurements, no statistically significant difference was detected in EF (41% at baseline, 42% at 6 months). Of the 16 patients with serial dysrhythmia data, there was a trend toward reduction of percent of patients with ventricular tachycardia (VT), from 32% at baseline, to 22% at 6 months and 19% at 12 months (p = 0.07). Adverse events were common, occurring in 6 of 36 patients, with 3 of 36 patients stopping infliximab for a prolonged period. In responder analysis, 24 patients improved in at least 1 of 3 outcome categories. In conclusion, infliximab may be useful for refractory cardiac sarcoidosis.

The double-bromodomain proteins Bdf1 and Bdf2 modulate chromatin structure to regulate S-phase stress response in Schizosaccharomyces pombe.

Bromodomain proteins bind acetylated histones to regulate transcription. Emerging evidence suggests that histone acetylation plays an important role in DNA replication and repair, although its precise mechanisms are not well understood. Here we report studies of two double bromodomain-containing proteins, Bdf1 and Bdf2, in fission yeast. Loss of Bdf1 or Bdf2 led to a reduction in the level of histone H4 acetylation. Both bdf1Δ and bdf2Δ cells showed sensitivity to DNA damaging agents, including camptothecin, that cause replication fork breakage. Consistently, Bdf1 and Bdf2 were important for recovery of broken replication forks and suppression of DNA damage. Surprisingly, deletion of bdf1 or bdf2 partially suppressed sensitivity of various checkpoint mutants including swi1Δ, mrc1Δ, cds1Δ, crb2Δ, chk1Δ, and rad3Δ, to hydroxyurea, a compound that stalls replication forks and activates the Cds1-dependent S-phase checkpoint. This suppression was not due to reactivation of Cds1. Instead, we found that bdf2 deletion alleviates DNA damage accumulation caused by defects in the DNA replication checkpoint. We also show that hydroxyurea sensitivity of mrc1Δ and swi1Δ was suppressed by mutations in histone H4 acetyltransferase subunits or histone H4. These results suggest that the double bromodomain-containing proteins modulate chromatin structure to coordinate DNA replication and S-phase stress response.