Effectiveness of mRNA Booster Vaccine Against Coronavirus Disease 2019 Infection and Severe Outcomes Among Persons With and Without Immune Dysfunction: A Retrospective Cohort Study of National Electronic Medical Record Data in the United States.

Background: Real-world evidence of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) booster effectiveness among patients with immune dysfunction are limited. Methods: We included data from patients in the United States National COVID Cohort Collaborative (N3C) who completed ≥2 doses of mRNA vaccination between 10 December 2020 and 27 May 2022. Immune dysfunction conditions included human immunodeficiency virus infection, solid organ or bone marrow transplant, autoimmune diseases, and cancer. We defined incident COVID-19 BTI as positive results from laboratory tests or diagnostic codes 14 days after at least 2 doses of mRNA vaccination; and severe COVID-19 BTI as hospitalization, invasive cardiopulmonary support, and/or death. We used propensity scores to match boosted versus nonboosted patients and evaluated hazards of incident and severe COVID-19 BTI using Cox regression after matching. Results: Among patients without immune dysfunction, the relative effectiveness of booster (3 doses) after 6 months from the primary (2 doses) vaccination against BTI ranged from 69% to 81% during the Delta-predominant period and from 33% to 39% during the Omicron-predominant period. Relative effectiveness against BTI was lower among patients with immune dysfunction but remained statistically significant in both periods. Boosted patients had lower risk of COVID-19-related hospitalization (hazard ratios [HR] ranged from 0.5 [95% confidence interval {CI}, .48-.53] to 0.63 [95% CI, .56-.70]), invasive cardiopulmonary support, or death (HRs ranged from 0.46 [95% CI, .41-.52] to 0.63 [95% CI, .50-.79]) during both periods. Conclusions: Booster vaccines remain effective against severe COVID-19 BTI throughout the Delta- and Omicron-predominant periods, regardless of patients' immune status.

Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.

Creation of a data commons for substance misuse related health research through privacy-preserving patient record linkage between hospitals and state agencies.

Objectives: Substance misuse is a complex and heterogeneous set of conditions associated with high mortality and regional/demographic variations. Existing data systems are siloed and have been ineffective in curtailing the substance misuse epidemic. Therefore, we aimed to build a novel informatics platform, the Substance Misuse Data Commons (SMDC), by integrating multiple data modalities to provide a unified record of information crucial to improving outcomes in substance misuse patients. Materials and Methods: The SMDC was created by linking electronic health record (EHR) data from adult cases of substance (alcohol, opioid, nonopioid drug) misuse at the University of Wisconsin hospitals to socioeconomic and state agency data. To ensure private and secure data exchange, Privacy-Preserving Record Linkage (PPRL) and Honest Broker services were utilized. The overlap in mortality reporting among the EHR, state Vital Statistics, and a commercial national data source was assessed. Results: The SMDC included data from 36 522 patients experiencing 62 594 healthcare encounters. Over half of patients were linked to the statewide ambulance database and prescription drug monitoring program. Chronic diseases accounted for most underlying causes of death, while drug-related overdoses constituted 8%. Our analysis of mortality revealed a 49.1% overlap across the 3 data sources. Nonoverlapping deaths were associated with poor socioeconomic indicators. Discussion: Through PPRL, the SMDC enabled the longitudinal integration of multimodal data. Combining death data from local, state, and national sources enhanced mortality tracking and exposed disparities. Conclusion: The SMDC provides a comprehensive resource for clinical providers and policymakers to inform interventions targeting substance misuse-related hospitalizations, overdoses, and death.

Insights into measuring health disparities using electronic health records from a statewide network of health systems: A case study.

Within Wisconsin, our residents experience some of the worst health disparities in the nation. Public reporting on disparities in the quality of care is important to achieving accountability for reducing disparities over time and has been associated with improvements in care. Disparities reporting using statewide electronic health records (EHR) data would allow efficient and regular reporting, but there are significant challenges with missing data and data harmonization. We report our experience in creating a statewide, centralized EHR data repository to support health systems in reducing health disparities through public reporting. We partnered with the Wisconsin Collaborative for Healthcare Quality (the "Collaborative"), which houses patient-level EHR data from 25 health systems including validated metrics of healthcare quality. We undertook a detailed assessment of potential disparity indicators (race and ethnicity, insurance status and type, and geographic disparity). Challenges for each indicator are described, with solutions encompassing internal (health system) harmonization, central (Collaborative) harmonization, and centralized data processing. Key lessons include engaging health systems in identifying disparity indicators, aligning with system priorities, measuring indicators already collected in the EHR to minimize burden, and facilitating workgroups with health systems to build relationships, improve data collection, and develop initiatives to address disparities in healthcare.

Relations of Current and Past Cancer with Severe Outcomes among 104,590 Hospitalized COVID-19 Patients: The COVID EHR Cohort at the University of Wisconsin.

BACKGROUND: There is mixed evidence about the relations of current versus past cancer with severe COVID-19 outcomes and how they vary by patient and cancer characteristics. METHODS: Electronic health record data of 104,590 adult hospitalized patients with COVID-19 were obtained from 21 United States health systems from February 2020 through September 2021. In-hospital mortality and ICU admission were predicted from current and past cancer diagnoses. Moderation by patient characteristics, vaccination status, cancer type, and year of the pandemic was examined. RESULTS: 6.8% of the patients had current (n = 7,141) and 6.5% had past (n = 6,749) cancer diagnoses. Current cancer predicted both severe outcomes but past cancer did not; adjusted odds ratios (aOR) for mortality were 1.58 [95% confidence interval (CI), 1.46-1.70] and 1.04 (95% CI, 0.96-1.13), respectively. Mortality rates decreased over the pandemic but the incremental risk of current cancer persisted, with the increment being larger among younger vs. older patients. Prior COVID-19 vaccination reduced mortality generally and among those with current cancer (aOR, 0.69; 95% CI, 0.53-0.90). CONCLUSIONS: Current cancer, especially among younger patients, posed a substantially increased risk for death and ICU admission among patients with COVID-19; prior COVID-19 vaccination mitigated the risk associated with current cancer. Past history of cancer was not associated with higher risks for severe COVID-19 outcomes for most cancer types. IMPACT: This study clarifies the characteristics that modify the risk associated with cancer on severe COVID-19 outcomes across the first 20 months of the COVID-19 pandemic. See related commentary by Egan et al., p. 3.

Smoking Status, Nicotine Medication, Vaccination, and COVID-19 Hospital Outcomes: Findings from the COVID EHR Cohort at the University of Wisconsin (CEC-UW) Study.

INTRODUCTION: Available evidence is mixed concerning associations between smoking status and COVID-19 clinical outcomes. Effects of nicotine replacement therapy (NRT) and vaccination status on COVID-19 outcomes in smokers are unknown. METHODS: Electronic health record data from 104 590 COVID-19 patients hospitalized February 1, 2020 to September 30, 2021 in 21 U.S. health systems were analyzed to assess associations of smoking status, in-hospital NRT prescription, and vaccination status with in-hospital death and ICU admission. RESULTS: Current (n = 7764) and never smokers (n = 57 454) did not differ on outcomes after adjustment for age, sex, race, ethnicity, insurance, body mass index, and comorbidities. Former (vs never) smokers (n = 33 101) had higher adjusted odds of death (aOR, 1.11; 95% CI, 1.06-1.17) and ICU admission (aOR, 1.07; 95% CI, 1.04-1.11). Among current smokers, NRT prescription was associated with reduced mortality (aOR, 0.64; 95% CI, 0.50-0.82). Vaccination effects were significantly moderated by smoking status; vaccination was more strongly associated with reduced mortality among current (aOR, 0.29; 95% CI, 0.16-0.66) and former smokers (aOR, 0.47; 95% CI, 0.39-0.57) than for never smokers (aOR, 0.67; 95% CI, 0.57, 0.79). Vaccination was associated with reduced ICU admission more strongly among former (aOR, 0.74; 95% CI, 0.66-0.83) than never smokers (aOR, 0.87; 95% CI, 0.79-0.97). CONCLUSIONS: Former but not current smokers hospitalized with COVID-19 are at higher risk for severe outcomes. SARS-CoV-2 vaccination is associated with better hospital outcomes in COVID-19 patients, especially current and former smokers. NRT during COVID-19 hospitalization may reduce mortality for current smokers. IMPLICATIONS: Prior findings regarding associations between smoking and severe COVID-19 disease outcomes have been inconsistent. This large cohort study suggests potential beneficial effects of nicotine replacement therapy on COVID-19 outcomes in current smokers and outsized benefits of SARS-CoV-2 vaccination in current and former smokers. Such findings may influence clinical practice and prevention efforts and motivate additional research that explores mechanisms for these effects.

The first 20 months of the COVID-19 pandemic: Mortality, intubation and ICU rates among 104,590 patients hospitalized at 21 United States health systems.

MAIN OBJECTIVE: There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. STUDY DESIGN AND METHODS: University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. RESULTS AND SIGNIFICANCE: The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. CONCLUSIONS: Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528).

Association Between Immune Dysfunction and COVID-19 Breakthrough Infection After SARS-CoV-2 Vaccination in the US.

Importance: Persons with immune dysfunction have a higher risk for severe COVID-19 outcomes. However, these patients were largely excluded from SARS-CoV-2 vaccine clinical trials, creating a large evidence gap. Objective: To identify the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among persons with or without immune dysfunction. Design, Setting, and Participants: This retrospective cohort study analyzed data from the National COVID Cohort Collaborative (N3C), a partnership that developed a secure, centralized electronic medical record-based repository of COVID-19 clinical data from academic medical centers across the US. Persons who received at least 1 dose of a SARS-CoV-2 vaccine between December 10, 2020, and September 16, 2021, were included in the sample. Main Outcomes and Measures: Vaccination, COVID-19 diagnosis, immune dysfunction diagnoses (ie, HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, and bone marrow transplantation), other comorbid conditions, and demographic data were accessed through the N3C Data Enclave. Breakthrough infection was defined as a COVID-19 infection that was contracted on or after the 14th day of vaccination, and the risk after full or partial vaccination was assessed for patients with or without immune dysfunction using Poisson regression with robust SEs. Poisson regression models were controlled for a study period (before or after [pre- or post-Delta variant] June 20, 2021), full vaccination status, COVID-19 infection before vaccination, demographic characteristics, geographic location, and comorbidity burden. Results: A total of 664 722 patients in the N3C sample were included. These patients had a median (IQR) age of 51 (34-66) years and were predominantly women (n = 378 307 [56.9%]). Overall, the incidence rate for COVID-19 breakthrough infection was 5.0 per 1000 person-months among fully vaccinated persons but was higher after the Delta variant became the dominant SARS-CoV-2 strain (incidence rate before vs after June 20, 2021, 2.2 [95% CI, 2.2-2.2] vs 7.3 [95% CI, 7.3-7.4] per 1000 person-months). Compared with partial vaccination, full vaccination was associated with a 28% reduced risk for breakthrough infection (adjusted IRR [AIRR], 0.72; 95% CI, 0.68-0.76). People with a breakthrough infection after full vaccination were more likely to be older and women. People with HIV infection (AIRR, 1.33; 95% CI, 1.18-1.49), rheumatoid arthritis (AIRR, 1.20; 95% CI, 1.09-1.32), and solid organ transplant (AIRR, 2.16; 95% CI, 1.96-2.38) had a higher rate of breakthrough infection. Conclusions and Relevance: This cohort study found that full vaccination was associated with reduced risk of COVID-19 breakthrough infection, regardless of the immune status of patients. Despite full vaccination, persons with immune dysfunction had substantially higher risk for COVID-19 breakthrough infection than those without such a condition. For persons with immune dysfunction, continued use of nonpharmaceutical interventions (eg, mask wearing) and alternative vaccine strategies (eg, additional doses or immunogenicity testing) are recommended even after full vaccination.

PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans.

Pregnancy is a physiological state of continuous adaptation to changing maternal and fetal nutritional needs, including a reduction of maternal insulin sensitivity allowing for appropriately enhanced glucose availability to the fetus. However, excessive insulin resistance in conjunction with insufficient insulin secretion results in gestational diabetes mellitus (GDM), greatly increasing the risk for pregnancy complications and predisposing both mothers and offspring to future metabolic disease. Here, we report a signaling pathway connecting pregnancy-associated plasma protein A (PAPPA) with adipose tissue expansion in pregnancy. Adipose tissue plays a central role in the regulation of insulin sensitivity, and we show that, in both mice and humans, pregnancy caused remodeling of adipose tissue evidenced by altered adipocyte size, vascularization, and in vitro expansion capacity. PAPPA is known to be a metalloprotease secreted by human placenta that modulates insulin-like growth factor (IGF) bioavailability through prolteolysis of IGF binding proteins (IGFBPs) 2, 4, and 5. We demonstrate that recombinant PAPPA can stimulate ex vivo human adipose tissue expansion in an IGFBP-5- and IGF-1-dependent manner. Moreover, mice lacking PAPPA displayed impaired adipose tissue remodeling, pregnancy-induced insulin resistance, and hepatic steatosis, recapitulating multiple aspects of human GDM. In a cohort of 6361 pregnant women, concentrations of circulating PAPPA are inversely correlated with glycemia and odds of developing GDM. These data identify PAPPA and the IGF signaling pathway as necessary for the regulation of maternal adipose tissue physiology and systemic glucose homeostasis, with consequences for long-term metabolic risk and potential for therapeutic use.

JITA: A Platform for Enabling Real Time Point-of-Care Patient Recruitment.

Timely accrual continues to be a challenge in clinical trials. The evolution of Electronic Health Record systems and cohort selection tools like i2b2 have improved identification of potential candidate participants. However, delays in receiving relevant patient information and lack of real time patient identification cause difficulty in meeting recruitment targets. The authors have designed and developed a proof of concept platform that informs authorized study team members about potential participant matches while the patient is at a healthcare setting. This Just-In-Time Alert (JITA) application leverages Health Level 7 (HL7) messages and parses them against study eligibility criteria using Amazon Web Services (AWS) cloud technologies. When required conditions are satisfied, the rules engine triggers an alert to the study team. Our pilot tests using difficult to recruit trials currently underway at the UMass Medical School have shown significant potential by generating more than 90 patient alerts in a 90-day testing timeframe.

Treatment of Facial Fractures at a Level 1 Trauma Center: Do Medicaid and Non-Medicaid Enrollees Receive the Same Care?

BACKGROUND: Timing of surgical treatment of facial fractures may vary with the patient age, injury type, and presence of polytrauma. Previous studies using national data sets have suggested that trauma patients with government insurance experience fewer operations, longer length of hospital stay (LOS), and worse outcomes compared with privately insured patients. The objective of this study is to compare treatment of facial fractures in patients with and without Medicaid insurance (excluding Medicare). METHODS: All adults with mandibular, orbital, and midface fractures at a Level 1 Trauma Center between 2009 and 2018 were included. Statistical analyses were performed to assess the differences in the frequency of surgery, time to surgery (TTS), LOS, and mortality based on insurance type. RESULTS: The sample included 1541 patients with facial fractures (mandible, midface, orbital), of whom 78.8% were male, and 13.1% (208) were enrolled in Medicaid. Mechanism of injury was predominantly assault for Medicaid enrollees and falls or motor vehicle accidents for non-Medicaid enrollees (P < 0.001). Patients with mandible and midface fractures underwent similar rates of surgical repair. Medicaid enrollees with orbital fractures underwent less frequent surgery for facial fractures (24.8% versus 34.7%, P = 0.0443) and had higher rates of alcohol and drug intoxication compared with non-Medicaid enrollees (42.8% versus 31.6%, P = 0.008). TTS, LOS, and mortality were similar in both groups with facial fractures. CONCLUSIONS: Overall, the treatment of facial fractures was similar regardless of the insurance type, but Medicaid enrollees with orbital fractures experienced less frequent surgery for facial fractures. Further studies are needed to identify specific socioeconomic and geographic factors contributing to these disparities in care.

SUPPORT-AF II: Supporting Use of Anticoagulants Through Provider Profiling of Oral Anticoagulant Therapy for Atrial Fibrillation: A Cluster-Randomized Study of Electronic Profiling and Messaging Combined With Academic Detailing for Providers Making Decisions About Anticoagulation in Patients With Atrial Fibrillation.

BACKGROUND: Previous provider-directed electronic messaging interventions have not by themselves improved anticoagulation use in patients with atrial fibrillation. Direct engagement with providers using academic detailing coupled with electronic messaging may overcome the limitations of the prior interventions. METHODS AND RESULTS: We randomized outpatient providers affiliated with our health system in a 2.5:1 ratio to our electronic profiling/messaging combined with academic detailing intervention. In the intervention, we emailed providers monthly reports of their anticoagulation percentage relative to peers for atrial fibrillation patients with elevated stroke risk (CHA2DS2-VASc ≥2). We also sent electronic medical record-based messages shortly before an appointment with an anticoagulation-eligible but untreated atrial fibrillation patient. Providers had the option to send responses with explanations for prescribing decisions. We also offered to meet with intervention providers using an academic detailing approach developed based on knowledge gaps discussed in provider focus groups. To assess feasibility, we tracked provider review of our messages. To assess effectiveness, we measured the change in anticoagulation for patients of intervention providers relative to controls. We identified 85 intervention and 34 control providers taking care of 3591 and 1908 patients, respectively; 33 intervention providers participated in academic detailing. More than 80% of intervention providers read our emails, and 98% of the time a provider reviewed our in-basket messages. Replies to messages identified patient refusal as the most common reason for patients not being on anticoagulation (11.2%). For the group of patients not on anticoagulation at baseline assigned to an intervention versus control provider, the adjusted percent increase in the use of anticoagulation over 6 months was 5.2% versus 7.4%, respectively (P=0.21). CONCLUSIONS: Our electronic messaging and academic detailing intervention was feasible but did not increase anticoagulation use. Patient-directed interventions or provider interventions targeting patients declining anticoagulation may be necessary to raise the rate of anticoagulation. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03583008.

Treatment of Acute Cholecystitis: Do Medicaid and Non-Medicaid Enrolled Patients Receive the Same Care?

BACKGROUND: Nationally, Medicaid enrollees with emergency surgical conditions experience worse outcomes overall when compared with privately insured patients. The goal of this study is to investigate disparities in the treatment of cholecystitis based on insurance type and to identify contributing factors. METHODS: Adults with cholecystitis at a safety-net hospital in Central Massachusetts from 2017-2018 were included. Sociodemographic and clinical characteristics were compared based on Medicaid enrollment status (Medicare excluded). Univariate and multivariate analyses were used to compare the frequency of surgery, time to surgery (TTS), length of stay (LOS), and readmission rates between groups. RESULTS: The sample (n = 203) included 69 Medicaid enrollees (34%), with a mean age of 44.4 years. Medicaid enrollees were younger (p = 0.0006), had lower levels of formal education (high school diploma attainment, p < 0.0001), were more likely to be unmarried (p < 0.0001), Non-White (p = 0.0012), and require an interpreter (p < 0.0001). Patients in both groups experienced similar rates of laparoscopic cholecystectomy, TTS, and LOS; however, Medicaid enrollees experienced more readmissions within 30 days of discharge (30.4% vs 17.9%, p < 0.001). CONCLUSION: Despite anticipated population differences, the treatment of acute cholecystitis was similar between Medicaid and Non-Medicaid enrollees, with the exception of readmission. Further research is needed to identify patient, provider, and/or population factors driving this disparity.

Treatment of appendicitis: Do Medicaid and non-Medicaid-enrolled patients receive the same care?

BACKGROUND: Studies using national data sets have suggested that insurance type drives a disparity in the care of emergency surgery patients. Large databases lack the granularity that smaller, single-institution series may provide. The goal of this study is to identify factors that may account for differences in care between Medicaid and non-Medicaid enrollees with appendicitis in central Massachusetts. METHODS: All adult patients with acute appendicitis in an academic medical center between 2010 and 2018 were included. Sociodemographic and clinical characteristics were compared according to Medicaid enrollment status. Analyses were performed to assess differences in the frequency of operative treatment, time to surgery, length of stay, and rates of readmission. RESULTS: The sample included 1,257 patients, 10.7% of whom (n = 135) were enrolled in Medicaid. The proportions of patients presenting with perforated appendicitis (28.9% vs 31.2%, P = .857) and undergoing laparoscopic appendectomy (96.3% vs 90.7%, P = .081) were similar between the 2 groups, as were length of stay (20 hours 30 minutes versus 22 hours 38 minutes, P = .109) and readmission rates (17.8% vs 14.5%, P = .683). Medicaid enrollees did experience somewhat greater time to surgery (6 hours 47 minutes versus 4 hours 49 minutes, P < .001). CONCLUSION: Despite anticipated differences in population, the treatment of appendicitis was similar between Medicaid and non-Medicaid enrollees. Medicaid enrollees experienced greater time to surgery; however, further studies are needed to explain this disparity in care.

Proton pump inhibitors increase the severity of hepatic encephalopathy in cirrhotic patients.

BACKGROUND: Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites, esophageal/gastric varices or encephalopathy. The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy (HE). Well established triggers for HE include infection, gastrointestinal bleeding, constipation, and medications. Alterations to the gut microbiome is one of the leading ammonia producers in the body, and therefore may make patients more susceptible to HE. AIM: To investigate the relationship between the use of proton pump inhibitors (PPIs) and HE in patients with cirrhosis. METHODS: This is a single center, retrospective analysis. Patients were included in the study with an admitting diagnosis of HE. The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria. The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course. Secondary outcomes included rate of infection, gastrointestinal bleeding within the last 12 mo, mean ammonia level, and model for end-stage liver disease scores at admission. RESULTS: The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group (P = 0.001). The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers (P = 0.046). Twenty-seven (31.8%) patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group (16.7%) (P = 0.138). Finally, 10 (11.8%) patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group (2.8%) (P = 0.220). CONCLUSION: Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.

Integration of genomic and clinical data augments surveillance of healthcare-acquired infections.

BACKGROUND: Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates. OBJECTIVE: To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review. METHODS: Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification. RESULTS: Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance. CONCLUSIONS: Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.

SUPPORT-AF: Piloting a Multi-Faceted, Electronic Medical Record-Based Intervention to Improve Prescription of Anticoagulation.

Background Only 50% of eligible atrial fibrillation ( AF ) patients receive anticoagulation ( AC ). Feasibility and effectiveness of electronic medical record (EMR)-based interventions to profile and raise provider AC percentage is poorly understood. The SUPPORT-AF (Supporting Use of AC Through Provider Profiling of Oral AC Therapy for AF) study aims to improve rates of adherence to AC guidelines by developing and delivering supportive tools based on the EMR to providers treating patients with AF. Methods and Results We emailed cardiologists and community-based primary care providers affiliated with our institution reports of their AC percentage relative to peers. We also sent an electronic medical record-based message to these providers the day before an appointment with an atrial fibrillation patient who was eligible but not receiving AC . The electronic medical record message asked the provider to discuss AC with the patient if he or she deemed it appropriate. To assess feasibility, we tracked provider review of our correspondence. We also tracked the change in AC for intervention providers relative to alternate primary care providers not receiving our intervention. We identified 3786, 1054, and 566 patients cared for by 49 cardiology providers, 90 community-based primary care providers, and 88 control providers, respectively. At baseline, the percentage of AC was 71.3%, 63.5%, and 58.3% for these 3 respective groups. Intervention providers reviewed our e-mails and electronic medical record messages 45% and 96% of the time, respectively. For providers responding, patient refusal was the most common reason for patients not being on AC (21%) followed by high bleeding risk (19%). At follow-up 10 weeks later, change in AC was no different for either cardiology or community-based primary care providers relative to controls (0.2% lower and 0.01% higher, respectively). Conclusions Our intervention profiling AC was feasible, but not sufficient to increase AC in our population.

Video capsule endoscopy as a tool for evaluation of obscure overt gastrointestinal bleeding in the intensive care unit.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy (VCE) is a minimally invasive tool that helps visualize the gastrointestinal tract from the esophagus to the right colon without the need for sedation or preparation. VCE is safe with very few contraindications. However, its role and safety profile in the intensive care unit (ICU) population have not been reported. The aim of this study is to evaluate the safety, efficacy, and feasibility of VCE use in ICU patients. PATIENTS AND METHODS: We conducted a single-center retrospective observational study of patients who underwent VCE for evaluation of obscure overt gastrointestinal bleeding in the ICU between 2008 and 2016. RESULTS: This study included 48 patients who were admitted to the UMass Memorial Medical Center ICUs for gastrointestinal bleeding. VCE was successfully completed in 43/48 (90 %) patients. The entire length of small bowel could be evaluated in 75 % and the source of bleeding was identified in 44 % of the patients. The most commonly identified source of bleeding included small bowel angioectasias, duodenal erosions/ulcers, and small bowel polyps. No major complications could be attributed to the VCE. Only 1 capsule was retained after 2 wk; however, there was no incidence of bowel obstruction, perforation, or capsule aspiration. CONCLUSIONS: This observational retrospective study demonstrates that VCE may be a safe, feasible, and effective diagnostic tool in evaluation of gastrointestinal bleeding in the ICU population with few complications. VCE may be a safe diagnostic prelude and be a guide to the correct therapeutic procedure if needed, in the context of patients who are seriously ill.

OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine.

We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS) and a suite of tools called Oncology Data Retrieval Systems (OncDRS). OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies.