Background: Glucocorticoids, the class of steroids used in management of asthma, have been observed to be associated with adverse events such as increased coagulation and inhibition of fibrinolysis. This study evaluated the risk of VTE in relation to the use of glucocorticoids in patients with asthma. Methods: We conducted a nested case–control study among patients aged 20– 59 years with asthma who received at least one glucocorticoid prescription during 1995– 2015 in the UK-based Clinical Practice Research Datalink GOLD. We used descriptive analyses and conditional logistic regression to evaluate the risk of VTE associated with glucocorticoid use. Results: The adjusted ORs (aORs) (95% CI) for VTE in patients exposed to glucocorticoids were 1.9 (1.6– 2.3), 1.4 (1.1– 1.8), and 1.2 (0.9– 1.5) for current, recent, and past glucocorticoid users, respectively, compared to the unexposed. The aORs (95% CI) for VTE in patients exposed to systemic glucocorticoid and inhaled glucocorticoids, compared to the unexposed, were 3.5 (2.7– 4.5) and 1.5 (1.3– 1.8), respectively. Conclusion: Current and systemic glucocorticoid use was associated with a dose-response increased risk of incident idiopathic VTE.

Background: Fabry disease (FD) is a rare lysosomal storage disease associated with glycolipid accumulation that impacts multiple physiological systems. We conducted a systematic literature review (SLR) to characterize the humanistic (quality of life [QoL]) and economic burden of FD.Methods: Searches were conducted in the Embase, MEDLINE^®, and MEDLINE^®In-Process databases from inception to January 19, 2022. Conference abstracts of specified congresses were manually searched. Additional searches were performed in the Cochrane and ProQuest databases for the humanistic SLR and the National Health Service Economic Evaluations Database for the economic SLR. Studies of patients with FD of any sex, race, and age, and published in the English language were included. There was no restriction on intervention or comparator. For the humanistic SLR, studies that reported utility data, database/registry-based studies, questionnaires/surveys, and cohort studies were included. For the economic SLR, studies reporting economic evaluations or assessing the cost of illness and resource use were included.Results: Of the 1363 records identified in the humanistic search, 36 studies were included. The most commonly used QoL assessments were the 36-item Short-Form Health Survey (n = 16), EQ-5D questionnaire descriptive system or visual analog scale (n = 9), and the Brief Pain Inventory (n = 8). Reduced QoL was reported in patients with FD compared with healthy populations across multiple domains, including pain, physical functioning, and depressive symptoms. Multiple variables—including sex, age, disease severity, and treatment status—impacted QoL. Of the 711 records identified in the economic burden search, 18 studies were included. FD was associated with high cost and healthcare resource use. Contributors to the cost burden included enzyme replacement therapy, healthcare, and social care. In the seven studies that reported health utility values, lower utility scores were generally associated with more complications (including cardiac, renal, and cerebrovascular morbidities) and with classical disease in males.Conclusion: FD remains associated with a high cost and healthcare resource use burden, and reduced QoL compared with healthy populations. Integrating information from QoL and economic assessments may help to identify interventions that are likely to be of most value to patients with FD.

The objective of this retrospective cohort study was to describe pre-treatment characteristics, treatment patterns, health resource use, and clinical outcomes among adults hospitalized with COVID-19 in the United States (US) who initiated common treatments for COVID-19. The Optum^® COVID-19 electronic health records database was used to identify patients >18 years, diagnosed with COVID-19, who were admitted to an inpatient setting and received treatments of interest for COVID-19 between September 2020 and January 2021. Patients were stratified into cohorts based on index treatment use. Patient demographics, medical history, care setting, medical procedures, subsequent treatment use, patient disposition, clinical improvement, and outcomes were summarized descriptively. Among a total of 26,192 patients identified, the most prevalent treatments initiated were dexamethasone (35.4%) and dexamethasone + remdesivir (14.9%), and dexamethasone was the most common subsequent treatment. At day 14 post-index, <10% of patients received any treatments of interest. Mean (standard deviation [SD]) patient age was 65.6 (15.6) years, and the most prevalent comorbidities included hypertension (44.8%), obesity (35.4%), and diabetes (25.7%). At the end of follow-up, patients had a mean (SD) 8.1 (6.6) inpatient days and 1.4 (4.1) days with ICU care. Oxygen supplementation, non-invasive, or invasive ventilation was required by 4.5%, 3.0%, and 3.1% of patients, respectively. At the end of follow-up, 84.2% of patients had evidence of clinical improvement, 3.1% remained hospitalized, 83.8% were discharged, 4% died in hospital, and 9.1% died after discharge. Although the majority of patients were discharged alive, no treatments appeared to alleviate the inpatient morbidity and mortality associated with COVID-19. This highlights an unmet need for effective treatment options for patients hospitalized with COVID-19.

Objectives: This systematic literature review aimed to identify studies assessing the clinical efficacy and real-world effectiveness of current and emerging treatments for Fabry disease. Methods: Searches of the MEDLINE, EMBASE, and Cochrane library databases, as well as relevant congress proceedings, were conducted to identify publications reporting on studies in patients of any age, sex, race, or ethnicity who received any approved or experimental treatment for Fabry disease, published before 17 June 2024. Results: Of 1881 publications screened, 234 reported data on renal, cardiac, cerebrovascular, and disease severity outcomes from 225 studies. The majority of reported studies were observational in nature (n = 150; 67%) and involved only adults (n = 172; 74%). Study designs and patient populations were highly heterogeneous, and cross-study conclusions about the effectiveness of different therapies could not be made. Enzyme replacement therapy (ERT) with agalsidase alfa or agalsidase beta stabilized renal function and cardiac structure in patients with Fabry disease. Early initiation of ERT in childhood or young adulthood was associated with better renal and cardiac outcomes than treatment initiation at a later age. The small number of comparator studies of agalsidase alfa and agalsidase beta suggested similar efficacy. Patients treated with migalastat and pegunigalsidase alfa also maintained stable renal function and cardiac structure. Conclusions: Overall, current treatments slow the progression of renal and cardiac decline in patients with Fabry disease. Large cohort studies with long-term follow-up and baseline stratification based on clinical phenotype are needed to address evidence gaps and provide clinicians with robust data to inform treatment decisions.

Introduction Chronic hypoparathyroidism is associated with higher risk of developing chronic kidney disease compared with the general population. This study evaluated changes in estimated glomerular filtration rate (eGFR) over a 5-year period in adult patients with chronic hypoparathyroidism treated with recombinant parathyroid hormone (1-84), rhPTH(1-84), compared with a historical control cohort of patients who did not receive rhPTH(1-84). Methods This retrospective cohort study included patients with chronic hypoparathyroidism treated with rhPTH(1-84) in the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309), and HEXT (NCT01199614 and continuation study NCT02910466) clinical trials. A historical control cohort who did not receive parathyroid hormone but who had enrollment criteria similar to those for the clinical trials was selected from the IBM® Explorys electronic medical record database (January 2007–August 2019). Outcomes of interest were the annual rate of change in eGFR from baseline (i.e., eGFR slope) and the predicted eGFR change from baseline at years 1 through 5. Results The study comprised 72 adult patients with chronic hypoparathyroidism treated with rhPTH(1-84) and 176 control patients who did not receive rhPTH(1-84). Over 5 years, eGFR remained stable in the rhPTH(1-84) cohort, whereas eGFR declined at a rate of 1.67 mL/min/1.73 m² per year in the control cohort (P < 0.001 for eGFR slope in the control cohort). At 5 years, predicted eGFR in the rhPTH(1-84) cohort increased from baseline by 1.21 mL/min/1.73 m², whereas eGFR in the control cohort declined by 10.36 mL/min/1.73 m², after adjusting for baseline variables. The difference in eGFR slopes between the cohorts over 5 years was 1.37 mL/min/1.73 m² per year (95% CI 0.62–2.13; P < 0.001). Conclusion Long-term treatment with rhPTH(1-84) was associated with stable eGFR compared with eGFR decline in the controls not treated with rhPTH(1-84). Preservation of renal function conferred by rhPTH(1-84) may benefit patients with chronic hypoparathyroidism by reducing risk of long-term renal complications.

Background: Mucopolysaccharidosis II (MPS II; Hunter syndrome) is a rare, X-linked, life-limiting lysosomal storage disease characterized by a deficiency in the activity of the enzyme iduronate-2-sulfatase. Accumulation of glycosaminoglycans in tissues and organs throughout the body causes cellular damage, leading to multisystemic disease manifestations. Patients generally require multidisciplinary care across a wide range of specialties. Objectives: The aims of this study were to assess the healthcare needs of patients with MPS II and to explore the impact of treatment on disease burden and healthcare resource utilization. Methods: A retrospective review of medical charts from 19 US sites was performed. Data were analyzed from 140 male patients diagnosed with MPS II (defined as a documented deficiency in iduronate-2-sulfatase) between 1997 and 2017. The prevalence and age at onset of clinical manifestations and extent and frequency of healthcare resource use were evaluated. Results: Of the patients in this study, 77.1% had received enzyme replacement therapy with intravenous idursulfase and 62.1% had cognitive impairment. The clinical burden among patients was substantial: almost all patients had ear, nose, and throat abnormalities (95.7%); musculoskeletal abnormalities (95.0%); and joint stiffness or abnormalities (90.7%). Of the most prevalent disease manifestations, facial dysmorphism and hepatosplenomegaly were documented the earliest (median age at first documentation of 3.8 years in both cases). Hospitalizations, emergency department visits, and outpatient visits were reported for 51.2%, 58.5%, and 93.5% of patients, respectively, with a frequency of 0.1, 0.2, and 3.0 per patient per year, respectively. Surgery was also common, with 91.1% of patients having undergone at least 1 surgical procedure. The clinical burden and prevalence and frequency of resource use were generally similar in patients who had received enzyme replacement therapy and in those who had not. Conclusions: These results add to our understanding of the natural history of MPS II and indicate that the disease burden and healthcare needs of patients with this progressive disease are extensive. Increased understanding of disease burden and resource use may enable the development of models of healthcare resource utilization in patients with MPS II and contribute to improvements in disease management and patient care.