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Abstract Acid suppressants are widely-used classes of medications linked to increased risks of aerodigestive infections. Prior studies of these medications as potentially reversible risk factors for COVID-19 have been conflicting. We aimed to determine the impact of chronic acid suppression use on COVID-19 infection risk while simultaneously evaluating the influence of social determinants of health to validate known and discover novel risk factors. We assessed the association of chronic acid suppression with incident COVID-19 in a 1:1 case–control study of 900 patients tested across three academic medical centers in California, USA. Medical comorbidities and history of chronic acid suppression use were manually extracted from health records by physicians following a pre-specified protocol. Socio-behavioral factors by geomapping publicly-available data to patient zip codes were incorporated. We identified no evidence to support an association between chronic acid suppression and COVID-19 (adjusted odds ratio 1.04, 95% CI 0.92–1.17, P = 0.515). However, several medical and social features were positive (Latinx ethnicity, BMI ≥ 30, dementia, public transportation use, month of the pandemic) and negative (female sex, concurrent solid tumor, alcohol use disorder) predictors of new infection. These findings demonstrate the value of integrating publicly-available databases with medical data to identify critical features of communicable diseases.
We present a patient with advanced AIDS admitted with recurrent shock of unclear aetiology, fevers, altered mental status and refractory cytopenias. His case posed a diagnostic challenge because evaluation of septic shock in the setting of advanced AIDS requires a time-consuming work-up for broad infectious aetiologies that can delay consideration of other diagnoses, including primary or secondary haemophagocytic lymphohistiocytosis (HLH). After this patient did not improve with supportive care and empiric antimicrobials, there was concern for HLH given that he met ≥5 of the HLH consortium criteria. He underwent bone marrow biopsy, which was non-diagnostic. Empiric therapy for HLH was initiated, but unfortunately, the patient died. Autopsy revealed extensive haemophagocytosis in the spleen, bone marrow and liver, confirming the diagnosis of HLH. Postmortem, his soluble CD-25 returned 18 890 pg/mL (<1033 pg/mL), and his serum HHV-8 PCR resulted positive. The diagnosis was HLH secondary to Human Herpes Virus 8 (HHV-8) in a patient with advanced AIDS.
G-protein (Gβγ)-mediated voltage-dependent inhibition of N- and P/Q-type Ca 2+ channels contributes to presynaptic inhibition and short-term synaptic plasticity. The voltage dependence derives from the dissociation of Gβγ from the inhibited channels, but the underlying molecular and biophysical mechanisms remain largely unclear. In this study we investigated the role in this process of Ca 2+ channel β subunit (Ca v β) and a rigid α-helical structure between the α-interacting domain (AID), the primary Ca v β docking site on the channel α 1 subunit, and the pore-lining IS6 segment. Gβγ inhibition of P/Q-type channels was reconstituted in giant inside-out membrane patches from Xenopus oocytes. Large populations of channels devoid of Ca v β were produced by washing out a mutant Ca v β with a reduced affinity for the AID. These β-less channels were still inhibited by Gβγ, but without any voltage dependence, indicating that Ca v β is indispensable for voltage-dependent Gβγ inhibition. A truncated Ca v β containing only the AID-binding guanylate kinase (GK) domain could fully confer voltage dependence to Gβγ inhibition. Gβγ did not alter inactivation properties, and channels recovered from Gβγ inhibition exhibited the same activation property as un-inhibited channels, indicating that Gβγ does not dislodge Ca v β from the inhibited channel. Furthermore, voltage-dependent Gβγ inhibition was abolished when the rigid α-helix between the AID and IS6 was disrupted by insertion of multiple glycines, which also eliminated Ca v β regulation of channel gating, revealing a pivotal role of this rigid α-helix in both processes. These results suggest that depolarization-triggered movement of IS6, coupled to the subsequent conformational change of the Gβγ-binding pocket through a rigid α-helix induced partly by the Ca v β GK domain, causes the dissociation of Gβγ and is fundamental to voltage-dependent Gβγ inhibition.
Safety-net hospitals (SNHs) and facilities are the cornerstone of healthcare services for the medically underserved. The burden of chronic liver disease-including end-stage manifestations of cirrhosis and liver cancer-is high and rising among populations living in poverty who primarily seek and receive care in safety-net settings. For many reasons related to social determinants of health, these individuals often present with delayed diagnoses and disease presentations, resulting in higher liver-related mortality. With recent state-based policy changes such as Medicaid expansion that impact access to insurance and critical health services, an overview of the body of literature on SNH care for chronic liver disease is timely and informative for the liver disease community. In this narrative review, we discuss controversies in the definition of a SNH and summarize the known disparities in the cascade of the care and management of common liver-related conditions: (1) steatotic liver disease, (2) liver cancer, (3) chronic viral hepatitis, and (4) cirrhosis and liver transplantation. In addition, we review the specific impact of Medicaid expansion on safety-net systems and liver disease outcomes and highlight effective provider- and system-level interventions. Lastly, we address remaining gaps and challenges to optimizing care for vulnerable populations with chronic liver disease in safety-net settings.
The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (N > 1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.
Publicly available geocoded social determinants of health and mobility datasets used in the analysis of "Chronic Acid Suppression and Social Determinants of COVID-19 Infection". These datasets are required for the analytical workflow shared on Github which demonstrates how the analysis in the manuscript was done using randomly generated samples to protect patient privacy. zcta_county_rel_10.txt - Population and housing density from the 2010 decennial census. Obtained from: https://www2.census.gov/geo/docs/maps-data/data/rel/zcta_county_rel_10.txt cre-2018-a11.csv - Community Resilience Estimates which is is the capacity of individuals and households to absorb, endure, and recover from the health, social, and economic impacts of a disaster such as a hurricane or pandemic. Data obtained from: https://www.census.gov/data/experimental-data-products/community-resilience-estimates.html
zcta_tract_rel_10.txt - Relationship between ZCTA and US Census tracts (used to map census tracts to ZCTA). Data obtained from: https://www.census.gov/geographies/reference-files/time-series/geo/relationship-files.html#par_textimage_674173622
mask-use-by-county.txt - Mask Use By County comes from a large number of interviews conducted online by the global data and survey firm Dynata at the request of The New York Times. The firm asked a question about mask use to obtain 250,000 survey responses between July 2 and July 14, enough data to provide estimates more detailed than the state level. Data obtained from: https://github.com/nytimes/covid-19-data/tree/master/mask-use
mobility_report_US.txt - Google mobility report which charts movement trends over time by geography, across different categories of places such as retail and recreation, groceries and pharmacies, parks, transit stations, workplaces, and residential. Data obtained from: https://github.com/ActiveConclusion/COVID19_mobility/blob/master/google_reports/mobility_report_US.csv
ACS2015_zctaallvars.csv - Social Deprivation Index is a composite measure of area level deprivation based on seven demographic characteristics collected in the American Community Survey (https://www.census.gov/programs-surveys/acs/) and used to quantify the socio-economic variation in health outcomes. Factors are: Income, Education, Employment, Housing, Household Characteristics, Transportation, Demographics. Data obtained from: https://www.graham-center.org/rgc/maps-data-tools/sdi/social-deprivation-index.html
