Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, is an autosomal recessive genetic disorder caused by different SMPD1 mutations. Historically, ASMD has been classified as Niemann-Pick disease (NPD) types A (NPD A) and B (NPD B). NPD A is associated with a uniformly devastating disease course, with rapidly progressing psychomotor degeneration, leading to death typically by the age of 3 years, most often from respiratory failure. In contrast, the clinical phenotype and life expectancy of patients with NPD B may vary widely. Almost all patients have hepatosplenomegaly and an atherogenic lipid profile, and most patients have interstitial lung disease with progressive impairment of pulmonary function and hematologic abnormalities including cytopenias. Other common clinical manifestations include liver dysfunction, heart disease, skeletal abnormalities and growth delays. Some patients with ASMD who survive beyond early childhood have intermediate phenotypes (variant NPD B) characterized by combinations of non-neurologic and mild to severe neurologic symptoms. The physical and psychosocial burden of illness in patients with NPD B is substantial. Common symptoms include shortness of breath, joint or limb pain, abdominal pain, bleeding and bruising. The disease often leads to chronic fatigue, limited physical or social activity and difficulties in performing daily activities or work. Many patients die before or in early adulthood, often from pneumonia/respiratory failure or liver failure. Available treatments are limited to symptom management and supportive care. An enzyme replacement therapy currently in clinical development is expected to be the first treatment addressing the underlying pathology of the disease. Early diagnosis and appropriate management are essential for reducing the risk of complications. While knowledge about ASMD is evolving, more evidence about ASMD and the natural history across the disease spectrum is needed, to improve disease recognition, timely diagnosis and appropriate disease management.

BackgroundWe examined the quality of adult epilepsy care using the Quality Indicators in Epilepsy Treatment (QUIET) measure, and variations in quality based on the source of epilepsy care.MethodsWe identified 311 individuals with epilepsy diagnosis between 2004 and 2007 in a tertiary medical center in New England. We abstracted medical charts to identify the extent to which participants received quality indicator (QI) concordant care for individual QI's and the proportion of recommended care processes completed for different aspects of epilepsy care over a two year period. Finally, we compared the proportion of recommended care processes completed for those receiving care only in primary care, neurology clinics, or care shared between primary care and neurology providers.ResultsThe mean proportion of concordant care by indicator was 55.6 (standard deviation = 31.5). Of the 1985 possible care processes, 877 (44.2%) were performed; care specific to women had the lowest concordance (37% vs. 42% [first seizure evaluation], 44% [initial epilepsy treatment], 45% [chronic care]). Individuals receiving shared care had more aspects of QI concordant care performed than did those receiving neurology care for initial treatment (53% vs. 43%; X2 = 9.0; p = 0.01) and chronic epilepsy care (55% vs. 42%; X2 = 30.2; p < 0.001).ConclusionsSimilar to most other chronic diseases, less than half of recommended care processes were performed. Further investigation is needed to understand whether a shared-care model enhances quality of care, and if so, how it leads to improvements in quality.

In pair-wise comparisons of active treatment arms to one another, results suggest vernakalant IV, propafenone IV and flecainide appear to be effective in achieving rapid cardioversion in patients with short duration AF compared to other agents. Application of these findings to clinical practice need to account for the variable comorbidity profiles of patients, important determinants in the selection of appropriate therapy for individual patients. Though best practice methods were used, further research comparing treatments through direct head-to-head comparisons may be warranted to confirm these findings and further inform clinical practice.

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Pulmonary alveolar proteinosis (PAP) is a rare syndrome of alveolar surfactant accumulation, resulting hypoxemic respiratory failure, and increased infection risk. Despite advances in our understanding of disease pathogenesis and the availability of improved diagnostics, the epidemiology and healthcare burden of PAP remain poorly defined. To determine the prevalence, and healthcare utilization and costs associated with PAP, we interrogated a large health insurance claims database containing comprehensive data for approximately 15 million patients in the United States. We also evaluated data from a referral-based diagnostic testing program collected over a 15-year period. The prevalence of PAP was determined to be 6.87 ± 0.33 per million in the general population, similar in males and females, and increased with age, however considering difficulties and delays in diagnosing this is likely a minimum estimate of true prevalence. PAP patients had significantly more comorbidities, health care utilization and associated costs compared to control patients precisely matched for age and gender. Between 2004 and 2018, 249 patients confirmed to have PAP were evaluated to identify the PAP-causing disease; 91.5% had autoimmune PAP, 3% had hereditary PAP caused by GM-CSF receptor mutations, 4% had secondary PAP, and 1.5% had congenital PAP. Considering the high diagnostic accuracy of serum GM-CSF autoantibody testing and predominance of autoimmune PAP, these results emphasize the importance of utilizing blood-based testing in PAP syndrome to identify the PAP-causing disease rather than invasive lung biopsies, resulting in earlier diagnosis, reduced morbidity and lower healthcare costs.