Vaccine-preventable hospitalisations in adult mental health service users: a population study.

BACKGROUND: Vaccine-preventable conditions cause preventable illness and may increase mortality in people living with mental illness. We examined how risks of hospitalisation for a wide range of vaccine-preventable conditions varied by age and sex among mental health (MH) service users. METHODS: Linked population data from New South Wales (NSW), Australia were used to identify vaccine-preventable hospitalisations (VPH) for 19 conditions from 2015 to 2020. Adult MH service users (n = 418 915) were compared to other NSW residents using incidence rates standardised for age, sex and socioeconomic status. Secondary analyses examined admissions for COVID-19 to September 2021. RESULTS: We identified 94 180 VPH of which 41% were influenza, 33% hepatitis B and 10% herpes zoster. MH service users had more VPH admissions [adjusted incidence rate ratio (aIRR) 3.2, 95% CI 3.1-3.3]. Relative risks were highest for hepatitis (aIRR 4.4, 95% CI 4.3-4.6), but elevated for all conditions including COVID-19 (aIRR 2.0, 95% CI 1.9-2.2). MH service users had a mean age of 9 years younger than other NSW residents at first VPH admission, with the largest age gap for vaccine-preventable pneumonias (11-13 years younger). The highest relative risk of VPH was among MH service users aged 45-65. CONCLUSIONS: MH service users have increased risk of hospitalisation for many vaccine-preventable conditions. This may be due to reduced vaccination rates, more severe illness requiring hospitalisation, greater exposure to infectious conditions or other factors. People living with mental illness should be prioritised in vaccination strategies.

Impact of Socioeconomic Status on Outcomes of Patients with Kawasaki Disease.

OBJECTIVE: To evaluate the association of neighborhood socioeconomic status (SES) with time to intravenous immunoglobulin treatment, length of stay (LOS), and coronary artery aneurysms (CAAs) in patients with Kawasaki disease. STUDY DESIGN: We examined the relationship of SES in 915 patients treated at a large academic center between 2000 and 2017. Neighborhood SES was measured using a US census-based score derived from 6 measures related to income, education, and occupation. Linear and logistic regression were used to examine the association of SES with number of days of fever at time of treatment, LOS, and CAA. RESULTS: Patients in the lowest SES quartile were treated later than patients with greater SES (7 [IQR 5, 9] vs 6 [IQR 5, 8] days, P = .01). Patients in the lowest SES quartile were more likely to be treated after 10 days of illness, with an OR 1.9 (95% CI 1.3-2.8). In multivariable analysis, SES remained an independent predictor of the number of days of fever at time of treatment (P = .01). Patients in the lowest SES quartile had longer LOS than patients with greater SES (3 [IQR 2, 5] vs 3 [IQR 2, 4], P = .007). In subgroup analysis of white children, those in the lowest SES quartile vs quartiles 2-4 were more likely to develop large/giant CAA 17 (12%) vs 30 (6%), P = .03. CONCLUSIONS: Lower SES is associated with delayed treatment, prolonged LOS, and increased risk of large/giant CAA. Novel approaches to diagnosis and education are needed for children living in low-SES neighborhoods.

Adipocytokines and Associations With Abnormal Body Composition in Rheumatoid Arthritis.

OBJECTIVE: We determined associations between adipokines and abnormal body composition in patients with rheumatoid arthritis (RA). METHODS: Combining data from three RA cohorts, whole-body dual-energy absorptiometry measures of appendicular lean mass and fat mass indices were converted to age-, sex-, and race- and ethnicity-specific Z scores. Lean mass relative to fat mass was determined based on prior methods. Independent associations between body composition profiles and circulating levels of adiponectin, leptin, and fibroblast growth factor (FGF)-21 were assessed using linear and logistic regression models adjusting for demographic characteristics and study cohort. We also determined the improvement in the area under the curve (AUC) for prediction of low lean mass when adipokines were added to predictive models that included clinical factors such as demographic characteristics, study, and body mass index (BMI). RESULTS: Among 419 participants, older age was associated with higher levels of all adipokines, whereas higher C-reactive protein level was associated with lower adiponectin levels and higher FGF-21 levels. Greater fat mass was strongly associated with lower adiponectin levels and higher leptin and FGF-21 levels. Higher levels of adiponectin, leptin, and FGF-21 were independently associated with low lean mass. The addition of adiponectin and leptin levels to regression models improved prediction of low lean mass when combined with demographic characteristics, study, and BMI (AUC 0.75 vs. 0.66). CONCLUSION: Adipokines are associated with both excess adiposity and low lean mass in patients with RA. Improvements in the prediction of body composition abnormalities suggest that laboratory screening could help identify patients with altered body composition who may be at greater risk of adverse outcomes.

Perspectives of Academic Oncologists About Offering Expanded Access to Investigational Drugs.

Importance: The expanded access (EA) pathway permits patients to be treated with investigational medical products outside clinical trials. Because cancer care is a common indication for which EA is sought and these efforts require physician management, understanding oncologists' perspectives can help illuminate factors influencing patient access. Objective: To learn how oncologists practicing at academic medical centers (AMCs) perceive EA and their role in offering it. Design, Setting, and Participants: This qualitative study used data from semistructured interviews conducted from February 2020 to September 2021 with a purposive sample of oncologists recruited from large, urban AMCs in the northeast United States. Oncologists who had submitted at least 1 single-patient EA request to the institutional review boards at the University of Pennsylvania, Children's Hospital of Philadelphia, NYU Langone Health, and Dana-Farber Cancer Institute from January 1, 2014, through January 31, 2020, were eligible to participate. Data were analyzed from July 2021 to March 2022. Main Outcomes and Measures: Interviews focused on oncologist practice demographics, experience with EA, factors relevant to decisions to pursue EA and comfort with those decisions, perspectives on oncologists' role in EA, perspectives on the FDA's role, and the Right to Try pathway to access investigational drugs. Results: Eligible oncologists were interviewed until thematic saturation was reached, resulting in 25 interviews; most participants were women (15 participants [60%]), reported primarily treating adult patients (15 participants [60%]), had more than 10 years of clinical experience (16 participants [64%]), and had submitted at least 2 single-patient EA requests to their institutional review boards during the relevant period (14 participants [56%]). Oncologists viewed EA as an important tool for securing what they determined to be the best treatment option for their patients based on their own expert assessment of available data. Interviewees reported that they would rather access interventions as commercially available products or through clinical trials; however, if the preferred option was not available through these means, they viewed pursuit of EA as part of their obligation to patients, while often recognizing the potential for inequities in the broader patient population beyond their institutions. Participating oncologists felt confident pursuing investigational drugs for treatment use, despite the absence of FDA marketing approval, and did not necessarily view EA as a last resort. Conclusions and Relevance: These findings indicate that oncologists practicing in large academic settings sought to treat patients with the interventions they deemed most likely to be beneficial, regardless of approval status. As such, they viewed EA as an unexceptional means to obtain promising products, although it remains unclear whether their confidence in evaluating investigational treatments was justified. Future research should examine whether oncologists outside large AMCs share this confidence, as differences may influence patient access to the EA treatment pathway.

Circulating Fibroblast Growth Factor-21 Levels in Rheumatoid Arthritis: Associations With Disease Characteristics, Body Composition, and Physical Functioning.

OBJECTIVE: This study evaluated associations between fibroblast growth factor (FGF)-21, an adipokine associated with metabolic stress, and adverse longitudinal changes in body composition and physical functioning in patients with rheumatoid arthritis (RA). METHODS: At baseline and follow-up, patients with RA aged 18-70 years completed whole-body dual-energy X-ray absorptiometry and peripheral quantitative computed tomography to quantify lean mass, fat mass, and muscle density. Dynamometry assessed muscle strength at the hand and knee, and physical functioning was measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). FGF-21 and inflammatory cytokines were measured at baseline. Linear and logistic regression analyses assessed associations between FGF-21 levels and both body composition and physical functioning over time. RESULTS: There were 113 patients with RA enrolled, and 84 (74%) returned for follow-up at a median of 2.68 years. At baseline, FGF-21 was associated with age, smoking, methotrexate use, adiposity, and inflammatory cytokines: tumor necrosis factor receptor type I, YKL-40, vascular endothelial growth factor (VEGF), and resistin. The highest FGF-21 quartile was associated with worse SPPB and HAQ. Higher baseline FGF-21 levels (per 1 SD) were associated with worsening in muscle density and area Z-scores (ß -0.06, 95% CI -0.12 to 0.008, P = 0.08; and ß -0.05, 95% CI -0.10 to 0.006, P = 0.08, respectively) and a greater probability of a clinically meaningful worsening of HAQ (OR 2.37, 95% CI 1.21-4.64, P = 0.01). The fourth FGF-21 quartile was associated with worsening of SPPB (ß -0.57, 95% CI -1.04 to -0.09, P = 0.02). CONCLUSION: FGF-21 levels are associated with obesity and inflammatory cytokines, and with worsening in physical functioning in RA. These data support the hypothesis that FGF-21 can identify patients at risk of functional decline.

Cyclophosphamide use in treatment of refractory Kawasaki disease with coronary artery aneurysms.

BACKGROUND: Despite timely administration of IVIG, some patients with Kawasaki disease (KD) develop rapidly progressive or giant coronary artery aneurysms (CAA). CASE PRESENTATION: We describe our experience using cyclophosphamide (CYC) for the treatment of such cases as well as a review of the literature on the use of CYC in KD. Through a retrospective chart review of our KD population, we identified ten children treated for KD with intravenous CYC (10 mg/kg/dose) for one or two doses. Seven patients were male, the median age was 2.0 years (range 4 months - 5 years). All patients received initial IVIG between day 4-10 of illness. Other anti-inflammatory treatments administered before CYC included second IVIG (n = 9), corticosteroids (n = 10), infliximab (n = 4), cyclosporine (n = 2), and anakinra (n = 1). Median illness day at administration of the first CYC dose was 22.5 days (range:10-36 days). The primary indication for treatment with CYC for all patients was large or giant CAA and/or rapid progression of CAA. Three patients received a second dose of CYC (10 mg/kg) for progressively enlarging CAA. CAA did not progress after final CYC treatment. One patient with a history of neutropenia in infancy developed severe neutropenia 9 days after treatment with CYC, which recovered without intervention or complications. No patient developed infections or other serious toxicity from CYC. CONCLUSION: In KD patients with severe and progressive enlargement of CAA despite anti-inflammatory therapy, CYC seemed to arrest further dilation and was well-tolerated. Future multicenter studies are needed to confirm our findings in this subgroup of KD patients.

Treatment Intensification in Patients With Kawasaki Disease and Coronary Aneurysm at Diagnosis.

BACKGROUND: Coronary artery aneurysms (CAA) are a serious complication of Kawasaki disease. Treatment with intravenous immunoglobulin (IVIg) within 10 days of fever onset reduces the risk of CAA from 25% to <5%. Corticosteroids and infliximab are often used in high-risk patients or those with CAA at diagnosis, but there are no data on their longer-term impact on CAA. METHODS: Retrospective multicenter study including children who had CAA with a z score ≥2.5 and <10 at time of diagnosis and who received primary therapy with IVIg alone or in combination with either corticosteroids or infliximab within 10 days of onset of fever. RESULTS: Of 121 children, with a median age of 2.8 (range 0.1-15.5) years, 30 (25%) received primary therapy with corticosteroids and IVIg, 58 (48%) received primary therapy with infliximab and IVIg, and 33 (27%) received primary therapy with IVIg only. Median coronary z scores at the time of diagnosis did not differ among treatment groups (P = .39). Primary treatment intensification with either corticosteroids or infliximab were independent protective factors against progression of coronary size on follow-up (coefficient: -1.31 [95% confidence interval: -2.33 to -0.29]; coefficient: -1.07 [95% confidence interval: -1.95 to -0.19], respectively). CONCLUSIONS: Among a high-risk group of patients with Kawasaki disease with CAA on baseline echocardiography, those treated with corticosteroids or infliximab in addition to IVIg had less progression in CAA size compared with those treated with IVIg alone. Prospective randomized trials are needed to determine the best adjunctive treatment of patients who present with CAA.

Navigating the Expanded Access Pathway to Investigational Drugs as an Academic Oncologist.

This qualitative study explores academic oncologists' needs and satisfaction with expanded patient access to investigational drugs.