Epidemiology and health outcomes of sarcoidosis in a universal healthcare population: a cohort study.

Sarcoidosis-related mortality appears to be rising in North America, with increasing rates in females and the elderly. We aimed to estimate trends in sarcoidosis incidence, prevalence and mortality in Ontario, Canada.We performed a cohort study using health administrative data from Ontario between 1996 and 2015. International Classification of Diseases and Ontario Health Insurance Plan codes were used for case detection. Three disease definitions were created: 1) sarcoidosis, two or more physician claims within 2 years; 2) chronic sarcoidosis, five or more physician claims within 3 years; and 3) sarcoidosis with histology, two or more physician claims with a tissue biopsy performed between claims.Overall, 18 550, 9199 and 3819 individuals with sarcoidosis, chronic sarcoidosis and sarcoidosis with histology, respectively, were identified. The prevalence of sarcoidosis was 143 per 100 000 in 2015, increasing by 116% (p<0.0001) from 1996. The increase in age-adjusted prevalence was higher in males than females (136% versus 99%; p<0.0001). The incidence of sarcoidosis declined from 7.9 to 6.8 per 100 000 between 1996 and 2014 (15% decrease; p=0.0009). A 30.3% decrease in incidence was seen among females (p<0.0001) compared with a 5.5% increase in males (p=0.47). Age- and sex-adjusted mortality rates of patients with sarcoidosis rose from 1.15% to 1.47% between 1996 and 2015 (28% increase; p=0.02), with the overall trend being nonsignificant (p=0.39). Mortality rates in patients with chronic sarcoidosis increased significantly over the study period (p=0.0008).The prevalence of sarcoidosis is rising in Ontario, with an apparent shifting trend in disease burden from females to males. Mortality is increasing in patients with chronic sarcoidosis.

A comprehensive evaluation of online inhaler use techniques for obstructive airway disease.

BACKGROUND: Pulmonary inhaler therapy is a core treatment modality for >600 million individuals affected by obstructive airways disease globally. Poor inhaler technique is associated with reduced disease control and increased health care utilization; however, many patients rely on the internet as a technical resource. This study assesses the content and quality of online resources describing inhaler techniques. METHODS: A Google search was conducted in April 2023 capturing the top 5 search results for 12 common inhaler devices. Websites were compared to product monographs for preparation/first use, inhalational technique, and post-usage/device care. They were also assessed using accepted quality metrics (GQS, DISCERN, JAMA Benchmark scores) and clinically relevant aspects based on the literature and consensus statements. RESULTS: Websites regularly excluded critical steps important for proper inhaler technique. They performed best on information related directly to inhalation technique (average median score 78%), whereas steps related to preparation/first use (58%) or post-usage/device care (50%) were less frequently addressed. Median GQS, DISCERN, and JAMA Benchmark scores were 3 [IQR 3-4], 3 [IQR 2-4], and 1 [IQR 1-3], respectively. Clinically relevant factors were only addressed in about one-fifth of websites with no websites addressing smoking cessation, environmental considerations, or risk factors for poor technique. CONCLUSIONS: This study highlights gaps in online resources describing inhaler technique, particularly related to preparation/first use and post-usage/device care steps. Clinically relevant factors were rarely addressed across websites. Improvements in these areas could lead to enhanced inhaler technique and clinical outcomes.

Myositis Antibodies and Interstitial Lung Disease.

BACKGROUND: Interstitial lung disease (ILD) comprises a heterogeneous group of inflammatory and fibrotic conditions, often resulting in progressive lung function decline and increased mortality. Connective tissue disease (CTD) should be considered in all patients with ILD, as distinguishing between CTD-ILD and other forms of fibrotic lung disease has important therapeutic and prognostic implications. The idiopathic inflammatory myopathies (IIM) represent a CTD subtype of growing interest to ILD experts. The expansion and availability of myositis-specific and myositis-associated antibody testing has allowed for improved disease detection and characterization. CONTENT: In this review, we highlight the relationship between myositis antibodies and ILD. Select forms of IIM, such as the antisynthetase syndrome and clinically amyopathic dermatomyositis can present with rapidly progressive ILD, warranting timely disease diagnosis and management. Disease phenotypes, prevalence, laboratory testing, prognosis, and management strategies are described according to select myositis antibodies. SUMMARY: Myositis antibodies provide valuable information for clinicians managing patients with ILD. This review aims to increase awareness of their role in disease detection, pathophysiology, and possibly therapeutics.

Hospitalizations in Sarcoidosis: A Cohort Study of a Universal Healthcare Population.

Rationale: Population-based analyses of hospitalization rates from countries with universal healthcare systems are lacking for patients with sarcoidosis. Objectives: To evaluate the long-term trends in hospitalization rates and risk factors for hospitalization in patients with sarcoidosis in Ontario, Canada. Methods: We performed a cohort study using health administrative data from Ontario, Canada, between 1996 and 2015. Patients with sarcoidosis were identified by using two or more physician visits and International Classification of Diseases codes. All-cause and sarcoidosis-related hospitalization rates were age and sex standardized. Hospitalization rates between groups were analyzed by using Cochran-Armitage and Breslow-Day tests. Associations between patient characteristics and hospitalization rates were evaluated by using multivariable Poisson regression. Results: In total, 18,550 individuals with sarcoidosis experienced 33,516 all-cause and 1,725 sarcoidosis-related hospitalizations. Adjusted all-cause hospitalization rates decreased from 206.4 to 152.1 per 1,000 cases between 1996 and 2015 (26% decrease; P < 0.001). The largest decrease in all-cause hospitalization occurred in patients 18-25 years old (67% decrease; P < 0.001). Adjusted sarcoidosis-related hospitalization rates decreased from 21.8 to 4.2 per 1,000 cases between 1996 and 2015 (81% decrease; P < 0.001). The decrease in sarcoidosis-related hospitalizations was largest in women compared with men (87% vs. 72%; P = 0.004) and in those 26-35 years old (91% reduction; P < 0.001). Lower income (risk ratio, 1.27 [1.18-1.37]; P < 0.001) and rural residence (risk ratio, 1.16 [1.08-1.24]; P < 0.001) were associated with increased all-cause hospitalizations. Conclusions: Hospitalization rates in patients with sarcoidosis have decreased over the past 20 years, most substantially in patients of younger age. Important differences in the risk of hospitalization exist on the basis of sex, socioeconomic factors, and geographic factors in patients with sarcoidosis.

Utility of anti-neutrophil cytoplasmic antibody screening in idiopathic interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is an established manifestation of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Autoimmune serologic screening is recommended by international consensus guidelines during the evaluation of idiopathic ILD, but ANCA testing only on a case-by-case basis. OBJECTIVE: We aimed to evaluate the role of ANCA screening in patients with idiopathic ILD. METHODS: We performed a retrospective review of patients seen between September 2015 and April 2017 in the ILD clinic at Toronto General Hospital. Patients referred with confirmed or suspected connective tissue disease were excluded. Patient demographics, symptoms, chest imaging, and pulmonary function testing was collected. We performed descriptive statistics based on the presence of ANCAs and estimated operating characteristics for ANCA screening. RESULTS: In total, 360 patients with idiopathic ILD were reviewed, 159 met study inclusion criteria and 4 (2.5%) tested positive for ANCAs. Two patients (1.2%) had elevated myeloperoxidase-ANCAs (MPO-ANCA) and 2 (1.2%) had elevated proteinase-3-ANCAs (PR3-ANCA). There were no significant associations between patient demographics and ANCAs. One patient (0.6%) with PR3-ANCAs was diagnosed with vasculitis following rheumatologic evaluation. Despite negative ANCA testing, 1 patient (0.6%) was diagnosed with vasculitis following rheumatologic evaluation. The sensitivity and specificity of ANCA screening for vasculitis in patients with ILD was calculated as 50% (95% CI, 1.3%-98.7%) and 98% (95%CI, 4.4-155.5) respectively. Negative and positive likelihood ratios were 0.5 (95%CI 0.1-2.0) and 26.2 (95%CI 4.4-155.5) respectively. CONCLUSION: ANCA screening in patients with idiopathic ILD rarely yields positive results. These results support an individualized approach to ANCA testing as opposed to widespread screening.

Ophthalmologic assessments in patients with newly diagnosed sarcoidosis: An observational study from a universal healthcare system.

INTRODUCTION: Consensus guidelines for the management of sarcoidosis recommend screening eye examinations for all patients, even in those without ocular symptoms. We aimed to determine the proportion of sarcoidosis patients that complete ophthalmologic evaluations and factors associated with their performance. METHODS: We identified patients with sarcoidosis using population health services data from Ontario, Canada between 1991 and 2019. Sarcoidosis was defined by ≥ 2 physician visits for sarcoidosis within a two-year period. Ophthalmologic evaluations were based on an optometrist or ophthalmologist visit within the year prior or two years following the diagnosis. We estimated correlations between the number of eye care professionals and proportion of sarcoidosis patients completing ophthalmologic assessments within regional health units. We evaluated for associations between ophthalmologic screening and patient characteristics using multivariable logistic regression. RESULTS: We identified 21,679 patients with sarcoidosis in Ontario. An ophthalmologic evaluation was performed in 14,751 (68.0%), with a similar number of individuals seeing ophthalmologists and optometrists (43.7% vs. 42.2%). The percentage of sarcoidosis patients undergoing an ophthalmologic evaluation within corresponding regional health units was moderately correlated with the number of practicing ophthalmologists (r = 0.64, p = 0.01), but not the number of optometrists (r = 0.08, p = 0.77). Patients who were older [OR per year 1.02 (95% CI 1.01-1.02), p < 0.001] and female [OR 1.54 (95% CI 1.44-1.63), p < 0.001] were more likely to complete ophthalmologic evaluations. Immigrants to Canada were less likely to undergo ophthalmologic assessments [OR 0.66 (95% CI 0.60-0.73), p < 0.001]. CONCLUSIONS: Most patients with sarcoidosis complete ophthalmologic examinations, though a substantial proportion does not. Young adults, men and immigrants were less likely to complete ophthalmologic evaluations. Limited access to ophthalmologists may at least in part explain why some sarcoidosis patients fail to complete ophthalmologic screening.

Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of cardiomyocyte intercalated disk proteins causing sudden death. Heterozygous mutations of the desmosomal protein plakophilin-2 (PKP-2) are the commonest genetic cause of ARVC. Abnormal gap junction connexin43 expression has been reported in autosomal dominant forms of ARVC (Naxos and Carvajal disease) caused by homozygous mutations of desmosomal plakoglobin and desmoplakin. In tissue culture, suppression of PKP-2 results in decreased expression of connexin43. We sought to characterize the expression and localization of connexin43 in patients with ARVC secondary to heterozygous PKP-2 mutations. Complete PKP-2 gene sequencing of 27 ARVC patients was utilized to identify mutant genotypes. Endomyocardial biopsies of identified carriers were then assessed by immunofluorescence to visualize intercalated disk proteins. N-cadherin was targeted to highlight intercalated disks, followed by counterstaining for PKP-2 or connexin43 using confocal double immunofluorescence microscopy. Immunofluorescence was quantified using an AdobeA Photoshop protocol, and colocalization coefficients were determined. PKP-2 siRNA experiments were performed in mouse cardiomyocyte (HL1) cell culture with Western blot analysis to assess connexin43 expression following PKP-2 suppression. Missense and frameshift mutations of the PKP-2 gene were found in four patients with biopsy material available for analysis. Immunofluorescent studies showed PKP-2 localization to the intercalated disk despite mutations, but associated with decreased connexin43 expression and abnormal colocalization. PKP-2 siRNA in HL1 culture confirmed decreased connexin43 expression. Reduced connexin43 expression and localization to the intercalated disk occurs in heterozygous human PKP-2 mutations, potentially explaining the delayed conduction and propensity to develop arrhythmias seen in this disease.