To develop, validate and implement algorithms to identify diabetic retinopathy (DR) cases and controls from electronic health care records (EHR)s. Methods : We developed and validated EHR-based algorithms to identify DR cases and individuals with type I or II diabetes without DR (controls) in three independent EHR systems: Vanderbilt University Medical Center Synthetic Derivative (VUMC), the VA Northeast Ohio Healthcare System (VANEOHS), and Massachusetts General Brigham (MGB). Cases were required to meet one of three criteria: 1) two or more dates with any DR ICD-9/10 code documented in the EHR, or 2) at least one affirmative health-factor or EPIC code for DR along with an ICD9/10 code for DR on a different day, or 3) at least one ICD-9/10 code for any DR occurring within 24 hours of an ophthalmology exam. Criteria for controls included affirmative evidence for diabetes as well as an ophthalmology exam. The algorithms, developed and evaluated in VUMC through manual chart review, resulted in a positive predictive value (PPV) of 0.93 for cases and negative predictive value (NPV) of 0.97 for controls. Implementation of algorithms yielded similar metrics in VANEOHS (PPV=0.94; NPV=0.86) and lower in MGB (PPV=0.84; NPV=0.76). In comparison, use of DR definition as implemented in Phenome-wide association study (PheWAS) in VUMC, yielded similar PPV (0.92) but substantially reduced NPV (0.48). Implementation of the algorithms to the Million Veteran Program identified over 62,000 DR cases with genetic data including 14,549 African Americans and 6,209 Hispanics with DR. We demonstrate the robustness of the algorithms at three separate health-care centers, with a minimum PPV of 0.84 and substantially improved NPV than existing high-throughput methods. We strongly encourage independent validation and incorporation of features unique to each EHR to enhance algorithm performance for DR cases and controls.

Despite research demonstrating the risks of using feeding tubes in persons with advanced dementia, they continue to be placed. The natural history of dysphagia among patients with advanced dementia has not been examined. We conducted a secondary analysis of a national cohort of persons with advanced dementia staying at a nursing home stay before hospitalization to examine (1) pre-hospitalization dysphagia prevalence and (2) risk of feeding tube placement during hospitalization based on preexisting dysphagia. A retrospective cohort study consisting of all nursing home (NH) residents (≥66 years) with advanced dementia (Cognitive Function Scale score ≥2), a hospitalization between 2013-2017, and a Minimum Data Set (MDS) 3.0 assessment within 120 days before hospitalization. Pre-hospitalization dysphagia status and surgically placed feeding tube insertion during hospitalization were determined by MDS 3.0 swallowing items and ICD-9 codes, respectively. A multivariate logistic model clustering on hospital was used to examine the association of dysphagia with percutaneous endoscopic gastrostomy (PEG) feeding tube placement after adjustment for confounders. Between 2013 and 2017, 889,983 persons with NH stay with advanced dementia (mean age: 84.5, SD: 7.5, and 63.5% female) were hospitalized. Pre-hospitalization dysphagia was documented in 5.4% (n = 47,574) and characterized by oral dysphagia (n = 21,438, 2.4%), pharyngeal dysphagia (n = 24,257, 2.7%), and general swallowing complaints/pain (n = 14,928, 1.7%). Overall, PEG feeding tubes were placed in 3529 patients (11.2%) with pre-hospitalization dysphagia, whereas 27,893 (88.8%) did not have pre-hospitalization dysphagia according to MDS 3.0 items. Feeding tube placement risk increased with the number of dysphagia items noted on the pre-hospitalization MDS (6 vs. 0 dysphagia variables: OR = 5.43, 95% CI: 3.19-9.27). Based on MDS 3.0 assessment, only 11% of PEG feeding tubes were inserted in persons with prior dysphagia. Future research is needed on whether this represents inadequate assessment or the impact of potentially reversible intercurrent illness resulting in feeding tube placement.

Pulmonary arterial hypertension (PAH) is characterized by endothelial cell (EC) dysfunction. There are no data from living patients to inform whether differential gene expression of pulmonary artery ECs (PAECs) can discern disease subtypes, progression and pathogenesis. We aimed to further validate our previously described method to propagate ECs from right heart catheter (RHC) balloon tips and to perform additional PAEC phenotyping. We performed bulk RNA sequencing of PAECs from RHC balloons. Using unsupervised dimensionality reduction and clustering we compared transcriptional signatures from PAH to controls and other forms of pulmonary hypertension. Select PAEC samples underwent single cell and population growth characterization and anoikis quantification. Fifty-four specimens were analyzed from 49 subjects. The transcriptome appeared stable over limited passages. Six genes involved in sex steroid signaling, metabolism, and oncogenesis were significantly upregulated in PAH subjects as compared to controls. Genes regulating BMP and Wnt signaling, oxidative stress and cellular metabolism were differentially expressed in PAH subjects. Changes in gene expression tracked with clinical events in PAH subjects with serial samples over time. Functional assays demonstrated enhanced replication competency and anoikis resistance. Our findings recapitulate fundamental biological processes of PAH and provide new evidence of a cancer-like phenotype in ECs from the central vasculature of PAH patients. This “cell biopsy” method may provide insight into patient and lung EC heterogeneity to advance precision medicine approaches in PAH.

PurposeGiven the expanding legal cannabis market in the U.S., it is vital to understand how context impacts cannabis use. Therefore, we explored the effect of cannabis cues and cannabis-use context on cannabis demand in 79 adults who reported smoking cannabis at least weekly. MethodsParticipants completed a single laboratory session consisting of four hypothetical marijuana purchase tasks (MPTs) involving either a typical use situation or a driving or sleep context. The MPTs were alternated with exposure to cannabis or neutral picture cues based on block randomization by gender. ResultsCannabis cues increased self-reported craving for cannabis (p =.044) but did not significantly alter demand (ps =0.093–0.845). In the driving context, participants demonstrated a significant reduction in cannabis demand, indicated by lower intensity (p <0.001), Omax (p <0.001), and Pmax (p <0.001), breakpoint (p =.003), and higher α (p <0.001). The sleep context was associated with significantly greater α (p <0.006) but nonsignificant effects for other indices (ps =0.123–0.707). Finally, cannabis cues increased Omax (p =.013) and breakpoint (p =.035) in the sleep context but not in the typical-use context. ConclusionsThese findings suggest that cannabis-use behavior is sensitive to contingencies surrounding driving after cannabis use and may also be sensitive to sleep contexts in the presence of cannabis cues. Since this is the first study to examine driving and sleep contexts, we caution against drawing broad conclusions until future research is conducted to replicate these findings.

In the United States, nearly 85,000 Veterans experienced homelessness during 2020, and thousands more are experiencing housing instability, representing a significant proportion of the population.1 Many Veterans experiencing homelessness are aging and have complex co-occurring medical, psychiatric, and substance use disorders. Homelessness and older age put Veterans at greater risk for age-related disorders, including Alzheimer's disease and related dementias (ADRD). We examined the rate of ADRD diagnosis for Veterans experiencing homelessness and housing instability compared to a matched cohort of stably housed Veterans over a nine-year period using cox proportional hazard models. In the matched cohort, 95% (n = 88,811) of Veterans were men, and 67% (n = 59,443) were White and were on average 63 years old (SD = 10.8). Veterans with housing instability had a higher hazard of 1.53 (95% confidence interval (CI) 1.50, 1.59) for ADRD compared to Veterans without housing instability. Veterans experiencing housing instability have a substantially higher risk of receiving an ADRD diagnosis than a matched cohort of stably housed Veterans. Health systems and providers should consider cognitive screening among people experiencing housing insecurity. Existing permanent supportive housing programs should consider approaches to modify wraparound services to support Veterans experiencing ADRD.

Using health records from the Department of Veterans Affairs (VA), the largest healthcare training platform in the United States, we estimated independent associations between the intensity of attending supervision of surgical residents and 30-day postoperation patient outcomes. Academic leaders do not agree on the level of autonomy from supervision to grant surgery residents to best prepare them to enter independent practice without risking patient outcomes. Secondary data came from a national, systematic 1:8 sample of n = 862,425 teaching encounters where residents were listed as primary surgeon at 122 VA medical centers from July 1, 2004, through September 30, 2019. Independent associations between whether attendings had scrubbed or not scrubbed on patient 30-day all-cause mortality, complications, and 30-day readmission were estimated using generalized linear-mixed models. Estimates were tested for any residual confounding biases, robustness to different regression models, stability over time, and validated using moderator and secondary factors analyses. After accounting for potential confounding factors, residents supervised by scrubbed attendings in 733,997 nonemergency surgery encounters had fewer deaths within 30 days of the operation by 14.2% [0.3%, 29.9%], fewer case complications by 7.9% [2.0%, 14.0%], and fewer readmissions by 17.5% [11.2%, 24.2%] than had attendings not scrubbed. Over the 15 study years, scrubbed surgery attendings may have averted an estimated 13,700 deaths, 43,600 cases with complications, and 73,800 readmissions. VA policies on attending surgeon supervision have protected patient safety while allowing residents in selected teaching encounters to have limited autonomy from supervision.

We sought to identify factors associated with right ventricular (RV) dysfunction and elevated pulmonary artery systolic pressure (PASP) and association with adverse outcomes in peripartum cardiomyopathy (PPCM). We conducted a multi-centre cohort study to identify subjects with PPCM with the following criteria: left ventricular ejection fraction (LVEF)<40%, development of heart failure within the last month of pregnancy or 5months of delivery, and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included a composite of (i) major adverse events (need for extracorporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation, or death) or (ii) recurrent heart failure hospitalization. RV function was obtained from echocardiogram reports. In total, 229 women (1993-2017) met criteria for PPCM. Mean age was 32.4±6.8years, 28% were of African descent, 50 (22%) had RV dysfunction, and 38 (17%) had PASP≥30mmHg. After a median follow-up of 3.4years (interquartile range 1.0-8.8), 58 (25%) experienced the composite outcome of adverse events. African descent, family history of cardiomyopathy, LVEF, and PASP were significant predictors of RV dysfunction. Using Cox proportional hazards models, we found that women with RV dysfunction were three times more likely to experience the adverse composite outcome: hazard ratio 3.21 (95% confidence interval: 1.11-9.28), P=0.03, in a multivariable model adjusting for age, race, body mass index, preeclampsia, hypertension, diabetes, kidney disease, and LVEF. Women with PASP≥30mmHg had a lower probability of survival free from adverse events (log-rank P=0.04). African descent and family history of cardiomyopathy were significant predictors of RV dysfunction. RV dysfunction and elevated PASP were significantly associated with a composite of major adverse cardiac events. This at-risk group may prompt closer monitoring or early referral for advanced therapies.

Abstract Background Influenza point of care (POC) testing can support rapid influenza detection and outbreak management in nursing homes (NHs). We hypothesize cost-free on-site access to influenza POC tests increases POC test use and influenza detection. A current study positions us to evaluate this hypothesis. Methods A prospective cohort of U.S. NHs enrolled in a comparative effectiveness trial of baloxavir versus oseltamivir for outbreak management through 2 influenza seasons, 2020-2022 (NCT05012189). We compared study NHs provided with influenza POC tests for use when clinically indicated to non-study facilities participating in weekly National Healthcare Safety Network (NHSN) reporting for occurrence of influenza outbreaks. For study facilities, we received reports upon influenza detection and directly surveyed them for POC use and influenza incidence. We compared study NHs and other NHSN NHs for reported influenza case rates. Results We recruited 586 facilities with an average of 89 long-stay residents and 120 Medicare certified beds which reported 185 new influenza activity in 159 facilities. Study test use frequency was reported (N=250), mean use was 28 tests per facility whether or not influenza was detected. Upon influenza detection, 52% of NHs initiated antiviral treatment or chemoprophylaxis on 1 or more residents. Study NHs reported 201 cases with a cumulative incidence of 3.7 cases per 1000 resident days versus 2,124 cases (1.7 per 1000) in non-participating NHs in the same period. Non-participating U.S. NHs had fewer beds (76 long-stay residents), 106 Medicare certified beds and less than half the rate of outbreak detection from study facilities. Conclusion NHs that participated in our prospective study reported influenza disproportionately more than other NHs reporting to NHSN. We interpret that the availability of easy-to-use and freely accessible rapid POC influenza tests positions NHs to detect better and manage influenza outbreaks. The ease of access to POC on-site tests may play a significant role and become a best practice approach in this positive outcome to improve influenza detection and support early intervention. Disclosures Yasin Abdul, MD, Genentech: Grant/Research Support Ed Davidson, PharmD, MPH, Genentech: Grant/Research Support Kevin McConeghy, PharmD, Genentech: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi-Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Kaley Hayes, PharmD, PhD, Sanofi Aventis: Grant/Research Support Lisa Han, MPH, Genentech: Grant/Research Support Melissa LaMantia, MA, Genentech: Grant/Research Support Elie Saade, MD, Envision Pharma: Speaker, Presenter|Johnson and Johnson: Speaker, Travel, Lodging|Protein Sciences Corp: Grant/Research Support|Sanofi Pasteur: Speaker, Travel, Lodging David Canaday, MD, Pfizer: Grant/Research Support Stefan Gravenstein, MD, MPH, CDC: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|GSK: Honoraria|Janssen: Advisor/Consultant|Janssen: Honoraria|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Grant/Research Support|Seqirus: Honoraria

Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur in patients who have experienced trauma. This comorbidity leads to a vicious cycle where PTSD symptoms beget heavy drinking and vice versa. There are no FDA-approved medications to treat PTSD-AUD; therefore, individuals suffering from this comorbidity are treated with medication approved to treat the disorders separately or with off-label pharmacological interventions. However, these medications are limited in their efficacy for treating PTSD-AUD comorbidity. Emerging research on the nonclassical psychedelic drug 3,4-methylenedioxymethamphetamine (MDMA) suggests that it may be an effective drug used in conjunction with psychotherapy. The following reviews the current research for clinical pharmacotherapies, as well as MDMA-integrative psychotherapy as they pertain to PTSD and AUD in isolation and co-occurrence. Future directions for the role of psychedelic-integrative therapy for the treatment of this comorbidity are discussed.