Background: Pulmonary edema is a cardinal feature of the life-threatening condition known as acute respiratory distress syndrome (ARDS). Patients with chronic alcohol abuse are known to be at increased risk of developing and dying from ARDS. Based upon preclinical data, we hypothesized that a history of chronic alcohol abuse in ARDS patients is associated with greater quantities and slower resolution of pulmonary edema compared with ARDS patients without a history of alcohol abuse.
Methods: A PiCCO™ transpulmonary thermodilution catheter was inserted into 35 patients within 72 hours of meeting American European Consensus Criteria definition of ARDS. Pulmonary edema was quantified as extravascular lung water (EVLW) and measured for up to 7 days in 13 patients with a history of chronic alcohol abuse and 22 patients without a history of chronic alcohol abuse.
Results: Mean EVLW was higher in patients with a history of chronic alcohol abuse (16.6 vs. 10.5 ml/kg, p < 0.0001). Patients with alcohol abuse had significantly greater EVLW over the duration of the study (RM-ANOVA p = 0.003). There was a trend towards slower resolution of EVLW in patients with a history of alcohol abuse (a decrease of 0.5 ml/kg vs. 2.4 ml/kg, p = 0.17) over the study period. A history of alcohol abuse conferred a greater than 3-fold increased risk of elevated EVLW [OR 3.16, (1.26 to 7.93)] using multivariate logistic regression analysis.
Conclusions: In patients who develop ARDS, alcohol abuse is associated with greater levels EVLW and a trend towards slower resolution of EVLW. Combined with mechanistic and preclinical evidence linking chronic alcohol consumption and ARDS, targeted therapies should be developed for these patients.
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Carlos del Rio;
Jennifer C. Elliott;
Lacey Critchley;
Daniel J. Feaster;
Deborah S. Hasin;
Raul N. Mandler;
Georgina Osorio;
Allan E. Rodriguez;
Lisa R. Metsch
Background: Substance use can reduce care engagement for individuals with HIV. However, little is known as to whether heavy drinkers differ from drug users. This study compares heavy drinkers, drug users, and those drinking heavily and using drugs on their HIV care engagement. Methods: HIV-infected adult inpatients (n = 801; 67% male; 78% Black) from 11 urban hospitals across the United States participated in a multisite clinical trial to improve patient engagement in HIV care and virologic outcomes. All participants drank heavily and/or used drugs, and had poorly controlled HIV. Participants reported care history at baseline. We compared heavy drinkers, drug users, and those both drinking heavily and using drugs (reference group) on their engagement in care. Results: Heavy drinkers reported lowest rates of lifetime HIV care, AOR = 0.59 (95% CI = 0.36, 0.97). Groups did not differ in recent care, prescription of HIV medication, medical mistrust, or patient-provider relationship. Drug users evidenced the best medication adherence, AOR = 2.38 (95% CI = 1.33, 4.23). Exploratory analyses indicated that drinkers had lower initial care engagement, but that it increased more rapidly with duration of known HIV infection, with similar rates of recent care. Drinkers had the lowest CD4 counts (B=-0.28, p < 0.0001), but no difference in viral load. Conclusions: Heavy drinkers were least likely to have ever been in HIV care. More research is needed to determine why heavy drinkers evidence the lowest initial care engagement and current CD4 counts, and whether drinking intervention early in infection may increase HIV care engagement.
Background
Genomic data have been collected by different institutions and companies and need to be shared for broader use. In a cross-site genomic data sharing system, a secure and transparent access control audit module plays an essential role in ensuring the accountability. A centralized access log audit system is vulnerable to the single point of attack and also lack transparency since the log could be tampered by a malicious system administrator or internal adversaries. Several studies have proposed blockchain-based access audit to solve this problem but without considering the efficiency of the audit queries. The 2018 iDASH competition first track provides us with an opportunity to design efficient logging and querying system for cross-site genomic dataset access audit. We designed a blockchain-based log system which can provide a light-weight and widely compatible module for existing blockchain platforms. The submitted solution won the third place of the competition. In this paper, we report the technical details in our system.
Methods
We present two methods: baseline method and enhanced method. We started with the baseline method and then adjusted our implementation based on the competition evaluation criteria and characteristics of the log system. To overcome obstacles of indexing on the immutable Blockchain system, we designed a hierarchical timestamp structure which supports efficient range queries on the timestamp field.
Results
We implemented our methods in Python3, tested the scalability, and compared the performance using the test data supplied by competition organizer. We successfully boosted the log retrieval speed for complex AND queries that contain multiple predicates. For the range query, we boosted the speed for at least one order of magnitude. The storage usage is reduced by 25%.
Conclusion
We demonstrate that Blockchain can be used to build a time and space efficient log and query genomic dataset audit trail. Therefore, it provides a promising solution for sharing genomic data with accountability requirement across multiple sites.
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Lynn M. Almli;
Adriana Lori;
Jacquelyn L. Meyers;
Jaemin Shin;
Negar Fani;
Adam X. Maihofer;
Caroline M. Nievergelt;
Alicia Smith;
Kristina B. Mercer;
Kimberly Kerley;
Jennifer M. Leveille;
Hao Feng;
Duna Abu-Amara;
Janine D. Flory;
Rachel Yehuda;
Charles R. Marmar;
Dewleen G. Baker;
Bekh Bradley-Davino;
Karestan C. Koenen;
Karen N Conneely;
Kerry Ressler
Excessive alcohol use is extremely prevalent in the United States, particularly among trauma-exposed individuals. While several studies have examined genetic influences on alcohol use and related problems, this has not been studied in the context of trauma-exposed populations. We report results from a genome-wide association study of alcohol consumption and associated problems as measured by the alcohol use disorders identification test (AUDIT) in a trauma-exposed cohort. Results indicate a genome-wide significant association between total AUDIT score and rs1433375 [N = 1036, P = 2.61 × 10 −8 (dominant model), P = 7.76 × 10 −8 (additive model)], an intergenic single-nucleotide polymorphism located 323 kb upstream of the sodium channel and clathrin linker 1 (SCLT1) at 4q28. rs1433375 was also significant in a meta-analysis of two similar, but independent, cohorts (N = 1394, P = 0.0004), the Marine Resiliency Study and Systems Biology PTSD Biomarkers Consortium. Functional analysis indicated that rs1433375 was associated with SCLT1 gene expression and cortical-cerebellar functional connectivity measured via resting state functional magnetic resonance imaging. Together, findings suggest a role for sodium channel regulation and cerebellar functioning in alcohol use behavior. Identifying mechanisms underlying risk for problematic alcohol use in trauma-exposed populations is critical for future treatment and prevention efforts.
Enhancing quality of prescribing practices for older adults discharged from the Emergency Department (EQUIPPED) aims to reduce the monthly proportion of potentially inappropriate medications (PIMs) prescribed to older adults discharged from the ED to 5% or less. We describe prescribing outcomes at three academic health systems adapting and sequentially implementing the EQUIPPED medication safety programme. EQUIPPED was adapted from a model developed in the Veterans Health Administration (VA) and sequentially implemented in one academic health system per year over a 3-year period. The monthly proportion of PIMs, as defined by the 2015 American Geriatrics Beers Criteria, of all medications prescribed to adults aged 65 years and older at discharge was assessed for 6 months preimplementation until 12 months postimplementation using a generalised linear time series model with a Poisson distribution. The EQUIPPED programme was translated from the VA health system and its electronic medical record into three health systems each using a version of the Epic electronic medical record. Adaptation occurred through local modification of order sets and in the generation and delivery of provider prescribing reports by local champions. Baseline monthly PIM proportions 6 months prior to implementation at the three sites were 5.6% (95% CI 5.0% to 6.3%), 5.8% (95% CI 5.0% to 6.6%) and 7.3% (95% CI 6.4% to 9.2%), respectively. Evaluation of monthly prescribing including the twelve months post-EQUIPPED implementation demonstrated significant reduction in PIMs at one of the three sites. In exploratory analyses, the proportion of benzodiazepine prescriptions decreased across all sites from approximately 17% of PIMs at baseline to 9.5%–12% postimplementation, although not all reached statistical significance. EQUIPPED is feasible to implement outside the VA system. While the impact of the EQUIPPED model may vary across different health systems, results from this initial translation suggest significant reduction in specific high-risk drug classes may be an appropriate target for improvement at sites with relatively low baseline PIM prescribing rates.
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Marina Serper;
Marijana Vujkovic;
David E. Kaplan;
Rotonya M. Carr;
Kyung Min Lee;
Qing Shao;
Donald R. Miller;
Peter D. Reaven;
Lawrence Phillips;
Christopher J. O'Donnell;
James B. Meigs;
Peter Wilson;
Rachel Vickers-Smith;
Henry R. Kranzler;
Amy C. Justice;
John M. Gaziano;
Sumitra Muralidhar;
Saiju Pyarajan;
Scott L. DuVall;
Themistocles L. Assimes;
Jennifer S. Lee;
Philip S. Tsao;
Daniel J. Rader;
Scott M. Damrauer;
Julie A. Lynch;
Danish Saleheen;
Benjamin F. Voight;
Kyong-Mi Chang
Background & aims
Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans.
Methods
MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts.
Results
Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen’s kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis.
Conclusions
We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.
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Jean Olivier Twahirwa Rwema;
Carrie E. Lyons;
Sara Herbst;
Benjamin Liestman;
Julien Nyombayire;
Sosthenes Ketende;
Amelia Mazzei;
Oluwasolape Olawore;
Sabin Nsanzimana;
Placidie Mugwaneza;
Aflodis Kagaba;
Patrick Sullivan;
Susan Allen;
Etienne Karita;
Stefan D. Baral
Introduction: Given intersecting biological, network and structural risks, men who have sex with men (MSM) and transgender women (TGW) consistently have a high burden of HIV. Although MSM are a key population in Rwanda, there are limited epidemiologic data to guide programming. This study aimed to characterize HIV prevalence and care cascade among MSM and TGW in Kigali. Methods: MSM and TGW ≥ 18 years were recruited using respondent-driven sampling (RDS) from March–August 2018 in Kigali. Participants underwent a structured interview including measures of individual, network and structural determinants. HIV and sexually transmitted infections (STI) including syphilis, Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) were tested. Viral load was measured for MSM living with HIV. Robust Poisson regression was used to characterize the determinants of HIV infection and engagement in the HIV treatment cascade. Results: A total of 736 participants were enrolled. The mean age was 27 years (range:18 to 68) and 14% (106) were TGW. HIV prevalence was 10% (RDS-adjusted: 9.2% (95% CI: 6.4 to 12.1)). Unadjusted prevalence of any STI was 20% (147); syphilis: 5.7% (42); CT: 9.1% (67) and NG: 8.8% (65). Anticipated (41%), perceived (36%) and enacted stigmas (45%) were common and higher among TGW (p < 0.001). In multivariable RDS adjusted analysis, higher age (aPR: 1.08 (95% CI: 1.05 to 1.12)) and ever having sex with women (aPR: 3.39 (95% CI: 1.31 to 8.72)) were positively associated with prevalent HIV. Being circumcised (aPR: 0.52 (95% CI: 0.28 to 0.9)) was negatively associated with prevalent HIV infection. Overall, 61% (45/74) of respondents reported knowing their HIV-positive status. Among these, 98% (44/45) reported antiretroviral therapy use (ART); 75% (33/44) were virally suppressed using a cut-off of <200 copies/mL. Of the 29 participants who did not report any previous HIV diagnosis or ART use, 38% (11/29) were virally suppressed. Cumulatively, 59% (44/74) of all participants living with HIV were virally suppressed. Conclusions: These data show a high burden of HIV among MSM/TGW in Kigali, Rwanda. Bisexual concurrency was common and associated with prevalent HIV infection, demonstrating the need of comprehensive screening for all sexual practices and preferences in the provision of comprehensive HIV prevention services in Rwanda. Viral suppression was below the UNAIDS target suggesting poor adherence and potential ART resistance. There is a need for adherence support, screening for primary and secondary ART resistance and stigma mitigation interventions to optimize HIV-related outcomes for MSM in Rwanda.
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Julie A. Womack;
Terrence E. Murphy;
Harini Bathulapalli;
Kathleen M. Akgun;
Cynthia Gibert;
Ken M. Kunisaki;
David Rimland;
Maria Rodriguez-Barradas;
H. Klar Yaggi;
Amy C. Justice;
Nancy S. Redeker
Background Linkage to and retention in care for US persons living with HIV (PLWH) after release from jail usually declines. We know of no rigorously evaluated behavioral interventions that can improve this. We hypothesized that a strengths-based case management intervention that we developed for PLWH leaving jail would increase linkage/retention in care (indicated by receipt of laboratory draws) and a suppressed HIV viral load (VL) in the year following release. Methods and findings We conducted a quasi-experimental feasibility study of our intervention for PLWH jailed in Atlanta. We recruited 113 PLWH in jail starting in 2014. “SUCCESS” (Sustained, Unbroken Connection to Care, Entry Services, and Suppression) began in jail and continued post-release. Subjects who started the intervention but subsequently began long-term incarcerations were excluded from further analysis. Persons who were retained in the intervention group were compared to contemporaneously incarcerated PLWH who did not receive the intervention. Identities were submitted to an enhanced HIV/AIDS reporting system (eHARS) at the state health department to capture all laboratories drawn. Both community engagement and care upon jail return were assessed equally. For 44 intervention participants released to Atlanta, 50% of care occurred on subsequent jail stays, as documented with EventFlow software. Forty-five receiving usual services only were recruited for comparison. By examining records of jail reentries, half of participants and 60% of controls recidivated (range: 1–8 returns). All but 6 participants in the intervention and 9 subjects in the comparison arm had 1 laboratory recorded in eHARS post-release. Among the intervention group, 52% were retained in care (i.e., had two laboratory studies, > = 3 months apart), versus 40% among the comparison group (OR = 1.60, 95% CI (0.71, 3.81)). Both arms showed improved viral load suppression. Conclusions There was a trend towards increased retention for PLWH released from jail after SUCCESS, compared to usual services. Measuring linkage at all venues, including jail-based clinics, fully captured engagement for this frequently recidivating population.
Background & Objective: Understanding the demographics of mortality and its burden in the emergency department of a tertiary care setup can lead to better planning and allocation of resources to streamline process flow. This can be achieved systematically through mortality audit that can identify the loopholes and areas of improvement. Our objective was to characterize the epidemiology of ED mortality in a tertiary care hospital of Karachi, Pakistan. Methods: A five-year retrospective chart review of 322 adult mortalities presenting between January l, 2014 – December 31, 2018 was conducted in the emergency department (ED) of The Indus Hospital (TIH), Karachi. All expiries in ED were included while those brought dead and with do not resuscitate order (DNAR) were excluded. Results: Mortality incidence of 0.076% (7.6/10,000 ED visits in five years) was reported. Amongst 507,759 adult ED visits, 322 mortalities were documented. Mean time lapse before presentation was 44±147 hours and mean length of stay before death was 3.4±2.8 hours. Acute coronary syndrome (ACS) was the predominant cause of death with 109 (33.8%) expiries. Significant association was reported between no history of prior care and high priority (P1) cases (p=0.013). Conclusions: This study identified the contributing factors to adverse outcome such as delayed presentation with systemic gaps in management and unknown disposition. The need to improve these factors at local and national level can lead to improvement in Pakistani healthcare sector.