Exposure-Response Relationship between VWF/FVIII Activity and Spontaneous Bleeding Events Following Recombinant VWF Prophylaxis in Severe VWD.

Background Recombinant von Willebrand factor (rVWF, vonicog alfa, Takeda Pharmaceuticals USA) is indicated in adults diagnosed with von Willebrand disease (VWD). In this study, the exposure-response (ER) relationship between VWF activity (VWF:RCo) or factor VIII activity (FVIII:C) and spontaneous bleeding events (BEs) was evaluated in adults with severe VWD receiving rVWF prophylaxis for up to 1 year. Methods This secondary analysis included 23 patients receiving rVWF prophylaxis in the open-label, phase 3 prophylaxis trial (NCT02973087). Population pharmacokinetic (PK) and PK/pharmacodynamic (PD) models were used to characterize VWF activity and endogenous FVIII:C, and PK/PD simulations were linked to spontaneous BEs to develop an ER model. Results None of the five patients with VWD types 1 or 2A/B experienced spontaneous BEs. Five of 18 patients with VWD type 3 experienced ≥1 spontaneous BEs. An ER relationship was observed whereby higher VWF:RCo levels were associated with a numerically lower spontaneous BE risk ( p < 0.10). This relationship was independent of patients' pretrial VWF treatment. A statistically significant ER relationship was observed after accounting for relevant data (average ± standard error exposure estimate for VWF:RCo over 24 hours prior to the spontaneous BE: -0.043 ± 0.021, p = 0.041). The model-generated hazard ratio for a 10 IU/dL increment in the average exposure of VWF:RCo 24 hours before a spontaneous BE was 0.651 (95% confidence interval: 0.431-0.982). Conclusions This ER analysis suggests a causal association between VWF:RCo and spontaneous BEs, with an increase of VWF:RCo exposure leading to a decrease in spontaneous BE risk.

Housing-Sensitive Health Conditions Can Predict Poor-Quality Housing.

Improving housing quality may improve residents' health, but identifying buildings in poor repair is challenging. We developed a method to improve health-related building inspection targeting. Linking New York City Medicaid claims data to Landlord Watchlist data, we used machine learning to identify housing-sensitive health conditions correlated with a building's presence on the Watchlist. We identified twenty-three specific housing-sensitive health conditions in five broad categories consistent with the existing literature on housing and health. We used these results to generate a housing health index from building-level claims data that can be used to rank buildings by the likelihood that their poor quality is affecting residents' health. We found that buildings in the highest decile of the housing health index (controlling for building size, community district, and subsidization status) scored worse across a variety of housing quality indicators, validating our approach. We discuss how the housing health index could be used by local governments to target building inspections with a focus on improving health.

Cognitive and adaptive behaviors associated with disease severity and genotype in patients with mucopolysaccharidosis II.

BACKGROUND: Mucopolysaccharidosis II (MPS II) is a rare, X-linked lysosomal storage disease caused by pathogenic variants of the iduronate-2-sulfatase gene (IDS) and is characterized by a highly variable disease spectrum. MPS II severity is difficult to predict based on IDS variants alone; while some genotypes are associated with specific phenotypes, the disease course of most genotypes remains unknown. This study aims to refine the genotype-phenotype categorization by combining information from the scientific literature with data from two clinical studies in MPS II. METHODS: Genotype, cognitive, and behavioral data from 88 patients in two clinical studies (NCT01822184, NCT02055118) in MPS II were analyzed post hoc in combination with published information on IDS variants from the biomedical literature through a semi-automated multi-stage review process. The Differential Ability Scales, second edition (DAS-II) and the Vineland Adaptive Behavior Scales™, second edition (VABS-II) were used to measure cognitive function and adaptive behavior. RESULTS: The most common category of IDS variant was missense (47/88, 53.4% of total variants). The mean (standard deviation [SD]) baseline DAS-II General Conceptual Ability (GCA) and VABS-II Adaptive Behavior Composite (ABC) scores were 74.0 (16.4) and 82.6 (14.7), respectively. All identified IDS complete deletions/large rearrangements (n = 7) and large deletions (n = 1) were associated with a published 'severe' or 'predicted severe' progressive neuronopathic phenotype, characterized by central nervous system involvement. In categories comprising more than one participant, mean baseline DAS-II GCA scores (SD) were lowest among individuals with complete deletions/large rearrangements 64.0 (9.1, n = 4) and highest among those with splice site variants 83.8 (14.2, n = 4). Mean baseline VABS-II ABC scores (SD) were lowest among patients with unclassifiable variants 79.3 (4.9, n = 3) and highest among those with a splice site variant 87.2 (16.1, n = 5), in variant categories with more than one participant. CONCLUSIONS: Most patients in the studies had an MPS II phenotype categorized as 'severe' or 'predicted severe' according to classifications, as reported in the literature. Patients with IDS complete deletion/large rearrangement variants had lower mean DAS-II GCA scores than those with other variants, as well as low VABS-II ABC, confirming an association with the early progressive 'severe' (neuronopathic) disease. These data provide a starting point to improve the classification of MPS II phenotypes and the characterization of the genotype-phenotype relationship.

Sensitivity of Medicaid Claims Data for Identifying Opioid Use Disorder in Patients Admitted to 6 New York City Public Hospitals.

OBJECTIVES: Behavioral health diagnoses are frequently underreported in administrative health data. For a pragmatic trial of a hospital addiction consult program, we sought to determine the sensitivity of Medicaid claims data for identifying patients with opioid use disorder (OUD). METHODS: A structured review of electronic health record (EHR) data was conducted to identify patients with OUD in 6 New York City public hospitals. Cases selected for review were adults admitted to medical/surgical inpatient units who received methadone or sublingual buprenorphine in the hospital. For cases with OUD based on EHR review, we searched for the hospitalization in Medicaid claims data and examined International Classification of Diseases, Tenth Revision discharge diagnosis codes to identify opioid diagnoses (OUD, opioid poisoning, or opioid-related adverse events). Sensitivity of Medicaid claims data for capturing OUD hospitalizations was calculated using EHR review findings as the reference standard measure. RESULTS: Among 552 cases with OUD based on EHR review, 465 (84.2%) were found in the Medicaid claims data, of which 418 (89.9%) had an opioid discharge diagnosis. Opioid diagnoses were the primary diagnosis in 49 cases (11.7%), whereas in the remainder, they were secondary diagnoses. CONCLUSION: In this sample of hospitalized patients receiving OUD medications, Medicaid claims seem to have good sensitivity for capturing opioid diagnoses. Although the sensitivity of claims data may vary, it can potentially be a valuable source of information about OUD patients.

Prophylaxis with recombinant von Willebrand factor in patients with type 3 von Willebrand disease: Results of a post hoc analysis from a phase 3 trial.

OBJECTIVES: To describe efficacy/safety of recombinant von Willebrand factor (rVWF) prophylaxis in patients with type 3 von Willebrand disease (VWD). METHODS: This post hoc analysis of a phase 3 open-label trial provides a more detailed analysis of adults with type 3 VWD, categorized based on prior treatment at screening: "Prior On-Demand (OD)" (OD VWF; ≥3 documented spontaneous bleeding events [BEs] requiring VWF in previous 12 months) or "Switch" (plasma-derived [pd] VWF prophylaxis for ≥12 months). Annualized bleeding rates (ABRs) were evaluated during 12 months of rVWF prophylaxis versus historical data from medical records. RESULTS: In the Prior OD group (n = 10), mean spontaneous ABR (sABR) for treated BEs was reduced by 91.6% (ratio, 0.08; 95% CI, 0.02-0.45) versus mean historical sABR. In the Switch group (n = 8), mean sABR for treated BEs was reduced by 47% (ratio, 0.53; 95% CI, 0.08-3.62). One non-serious adverse event (AE) was considered possibly related to rVWF. No treatment-related, fatal, or life-threatening serious AEs were reported, and no patient developed VWF inhibitors. CONCLUSIONS: rVWF prophylaxis reduced sABR in type 3 VWD patients previously treated with OD VWF therapy, and maintained a similar level of hemostatic control in those switching from pdVWF prophylaxis to rVWF prophylaxis.

Changes in the Public Charge Rule and Health of Mothers and Infants Enrolled in New York State's Medicaid Program, 2014‒2019.

Objectives. To examine the effect of the January 2017 leak of the federal government's intent to broaden the public charge rule (making participation in some public programs a barrier to citizenship) on immigrant mothers and newborns in New York State. Methods. We used New York State Medicaid data (2014-2019) to measure the effects of the rule leak (January 2017) on Medicaid enrollment, health care utilization, and severe maternal morbidity among women who joined Medicaid during their pregnancies and on the birth weight of their newborns. We repeated our analyses using simulated measures of citizenship status. Results. We observed an immediate statewide delay in prenatal Medicaid enrollment by immigrant mothers (odds ratio = 1.49). Using predicted citizenship, we observed significantly larger declines in birth weight (-56 grams) among infants of immigrant mothers. Conclusions. Leak of the public charge rule was associated with a significant delay in prenatal Medicaid enrollment among immigrant women and a significant decrease in birth weight among their newborns. Local public health officials should consider expanding health access and outreach programs to immigrant communities during times of pervasive antiimmigrant sentiment. (Am J Public Health. 2022; 112(12):1747-1756. https://doi.org/10.2105/AJPH.2022.307066).

Impact of aeroplane noise on mental and physical health: a quasi-experimental analysis.

OBJECTIVES: Historically, departures at New York City's LaGuardia airport flew over a large sports complex within a park. During the US Open tennis games, flights were diverted to fly over a heavily populated foreign-born neighbourhood for roughly 2 weeks out of the year so that the tennis match was not disturbed (the 'TNNIS' departure). In 2012, the use of the TNNIS departure became year-round to better optimise flight patterns around the metropolitan area. METHODS: We exploited exogenously induced spatial and temporal variation in flight patterns to examine difference-in-difference effects of this new exposure to aircraft noise on the health of individual residents in the community relative to individuals residing within a demographically similar community that was not impacted. We used individual-level Medicaid records, focusing on conditions associated with noise: sleep disturbance, psychological stress, mental illness, substance use, and cardiovascular disease. RESULTS: We found that increased exposure to aeroplane noise was associated with a significant increase in insomnia across all age groups, but particularly in children ages 5-17 (OR=1.64, 95% CI=1.12 to 2.39). Cardiovascular disease increased significantly both among 18-44-year-old (OR=1.45, 95% CI=1.41 to 1.49) and 45-64-year-old Medicaid recipients (OR=1.15, 95% CI=1.07 to 1.25). Substance use and mental health-related emergency department visits also increased. For ages 5-17,rate ratio (RR) was 4.11 (95% CI=3.28 to 5.16); for ages 18-44, RR was 2.46 (95% CI=2.20 to 2.76); and for ages 45-64, RR was 1.48 (95% CI=1.31 to 1.67). CONCLUSION: We find that increased exposure to aeroplane noise was associated with an increase in diagnosis of cardiovascular disease, substance use/mental health emergencies and insomnia among local residents.

Not a New Story: Place- and Race-Based Disparities in COVID-19 and Influenza Hospitalizations among Medicaid-Insured Adults in New York City.

While SARS-CoV-2 is a novel virus, contagious respiratory illnesses are not a new problem. Limited research has examined the extent to which place- and race-based disparities in severe illness are similar across waves of the COVID-19 pandemic and historic influenza seasons. In this study, we focused on these disparities within a low-income population, those enrolled in Medicaid in New York City. We used 2015-2020 New York State Medicaid claims to compare the characteristics of patients hospitalized with COVID-19 during three separate waves of 2020 (first wave: January 1-April 30, 2020; second wave: May 1-August 31, 2020; third wave: September 1-December 31, 2020) and with influenza during the 2016 (July 1, 2016-June 30, 2017) and 2017 influenza seasons (July 1, 2017-June 30, 2018). We found that patterns of hospitalization by race/ethnicity and ZIP code across the two influenza seasons and the first wave of COVID-19 were similar (increased risk among non-Hispanic Black (aOR = 1.17, 95% CI: 1.10-1.25) compared with non-Hispanic white Medicaid recipients). Black/white disparities in hospitalization dissipated in the second COVID wave and reversed in the third wave. The commonality of disparities across influenza seasons and the first wave of COVID-19 suggests there are community factors that increase hospitalization risk across novel respiratory illness incidents that emerge in the period before aggressive public health intervention. By contrast, convergence in hospitalization patterns in later pandemic waves may reflect, in part, the distinctive public health response to COVID-19.

Eviction, Healthcare Utilization, and Disenrollment Among New York City Medicaid Patients.

INTRODUCTION: Although growing evidence links residential evictions to health, little work has examined connections between eviction and healthcare utilization or access. In this study, eviction records are linked to Medicaid claims to estimate short-term associations between eviction and healthcare utilization, as well as Medicaid disenrollment. METHODS: New York City eviction records from 2017 were linked to New York State Medicaid claims, with 1,300 evicted patients matched to 261,855 non-evicted patients with similar past healthcare utilization, demographics, and neighborhoods. Outcomes included patients' number of acute and ambulatory care visits, healthcare spending, Medicaid disenrollment, and pharmaceutical prescription fills during 6 months of follow-up. Coarsened exact matching was used to strengthen causal inference in observational data. Weighted generalized linear models were then fit, including censoring weights. Analyses were conducted in 2019-2021. RESULTS: Eviction was associated with 63% higher odds of losing Medicaid coverage (95% CI=1.38, 1.92, p<0.001), fewer pharmaceutical prescription fills (incidence rate ratio=0.68, 95% CI=0.52, 0.88, p=0.004), and lower odds of generating any healthcare spending (OR=0.72, 95% CI=0.61, 0.85, p<0.001). However, among patients who generated any spending, average spending was 20% higher for those evicted (95% CI=1.03, 1.40, p=0.017), such that evicted patients generated more spending on balance. Marginally significant estimates suggested associations with increased acute, and decreased ambulatory, care visits. CONCLUSIONS: Results suggest that eviction drives increased healthcare spending while disrupting healthcare access. Given previous research that Medicaid expansion lowered eviction rates, eviction and Medicaid disenrollment may operate cyclically, accumulating disadvantage. Preventing evictions may improve access to care and lower Medicaid costs.

Public transportation and transmission of viral respiratory disease: Evidence from influenza deaths in 121 cities in the United States.

One important concern around the spread of respiratory infectious diseases has been the contribution of public transportation, a space where people are in close contact with one another and with high-use surfaces. While disease clearly spreads along transportation routes, there is limited evidence about whether public transportation use itself is associated with the overall prevalence of contagious respiratory illnesses at the local level. We examine the extent of the association between public transportation and influenza mortality, a proxy for disease prevalence, using city-level data on influenza and pneumonia mortality and public transit use from 121 large cities in the United States (US) between 2006 and 2015. We find no evidence of a positive relationship between city-level transit ridership and influenza/pneumonia mortality rates, suggesting that population level rates of transit use are not a singularly important factor in the transmission of influenza.

Integrating Behavioral Health and Primary Care Services for People with Serious Mental Illness: A Qualitative Systems Analysis of Integration in New York.

People with co-occurring behavioral and physical conditions receive poorer care through traditional health care services. One solution has been to integrate behavioral and physical care services. This study assesses efforts to integrate behavioral health and primary care services in New York. Semi-structured interviews were conducted with 52 professionals in either group or individual settings. We aimed to identify factors which facilitate or hinder integration for people with serious mental illness and how these factors inter-relate. Content analysis identified structural, process, organizational ("internal") and contextual ("external") themes that were relevant to integration of care. Network analysis delineated the interactions between these. We show that effective integration does not advance along a single continuum from minimally to fully integrated care but along several, parallel pathways reliant upon consequential factors that aid or hinder one another.