Rural-urban Differences in Long-term Mortality and Readmission Following COVID-19 Hospitalization, 2020 to 2023.

Background: We compared long-term mortality and readmission rates after COVID-19 hospitalization based on rural-urban status and assessed the impact of COVID-19 vaccination introduction on clinical outcomes by rurality. Methods: The study comprised adults hospitalized for COVID-19 at 17 hospitals in 4 US states between March 2020 and July 2022, followed until May 2023. The main analysis included all patients, whereas a sensitivity analysis focused on residents from 4 states containing 17 hospitals. Additional analyses compared the pre- and postvaccination periods. Results: The main analysis involved 9325 COVID-19 hospitalized patients: 31% were from 187 rural counties in 31 states; 69% from 234 urban counties in 44 states; the mean age was 65 years (rural, 66 years; urban, 64 years); 3894 women (rural, 41%; urban, 42%); 8007 Whites (rural, 87%; urban, 83%); 1738 deaths (rural, 21%; urban, 17%); and 2729 readmissions (rural, 30%; urban, 29%). During a median follow-up of 602 days, rural residence was associated with a 22% higher all-cause mortality (log-rank, P < .001; hazard ratio, 1.22; 95% confidence interval, 1.10-1.34, P < .001), and a trend toward a higher readmission rate (log-rank, P = .038; hazard ratio, 1.06; 95% confidence interval, .98-1.15; P = .130). The results remained consistent in the sensitivity analysis and in both pre- and postvaccination time periods. Conclusions and Relevance: Patients from rural counties experienced higher mortality and tended to be readmitted more frequently following COVID-19 hospitalization over the long term compared with those from urban counties, a difference that remained even after the introduction of COVID-19 vaccines.

Symptom presentation by phenotype of postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) presents heterogeneously and is diagnosed when appropriate symptoms are present in conjunction with a heart rate increase of at least 30 beats-per-minute upon standing without orthostatic hypotension. Much of the current understanding of POTS is based on clinical expertise, particularly regarding POTS phenotypes and their potential role in targeting pharmacologic treatment. This study describes the symptom presentation of POTS by phenotypes at a subspecialty POTS clinic. Data was collected prospectively during clinical visits between April 17, 2014 and February 8, 2021. This data was abstracted retrospectively by chart review. Most of the 378 study participants were female (89.9%) with a mean age 23.0 ± 4.9 years. Lightheadedness was the most common (97.6%) symptom and the most disruptive of quality of life (29.9%). Patients reported substantial functional impairment across multiple life domains, with 3.0 ± 2.8 days lost and 4.7 ± 2.3 unproductive days per week. There were no differences in symptom presentation among POTS phenotypes. POTS phenotypes are not distinguishable based on symptoms alone; if phenotyping is sought, testing is necessary. Further research is needed in better classifying POTS phenotypes with the potential goal of tailoring treatment.

An artificial intelligence approach for predicting death or organ failure after hospitalization for COVID-19: development of a novel risk prediction tool and comparisons with ISARIC-4C, CURB-65, qSOFA, and MEWS scoring systems.

BACKGROUND: We applied machine learning (ML) algorithms to generate a risk prediction tool [Collaboration for Risk Evaluation in COVID-19 (CORE-COVID-19)] for predicting the composite of 30-day endotracheal intubation, intravenous administration of vasopressors, or death after COVID-19 hospitalization and compared it with the existing risk scores. METHODS: This is a retrospective study of adults hospitalized with COVID-19 from March 2020 to February 2021. Patients, each with 92 variables, and one composite outcome underwent feature selection process to identify the most predictive variables. Selected variables were modeled to build four ML algorithms (artificial neural network, support vector machine, gradient boosting machine, and Logistic regression) and an ensemble model to generate a CORE-COVID-19 model to predict the composite outcome and compared with existing risk prediction scores. The net benefit for clinical use of each model was assessed by decision curve analysis. RESULTS: Of 1796 patients, 278 (15%) patients reached primary outcome. Six most predictive features were identified. Four ML algorithms achieved comparable discrimination (P > 0.827) with c-statistics ranged 0.849-0.856, calibration slopes 0.911-1.173, and Hosmer-Lemeshow P > 0.141 in validation dataset. These 6-variable fitted CORE-COVID-19 model revealed a c-statistic of 0.880, which was significantly (P < 0.04) higher than ISARIC-4C (0.751), CURB-65 (0.735), qSOFA (0.676), and MEWS (0.674) for outcome prediction. The net benefit of the CORE-COVID-19 model was greater than that of the existing risk scores. CONCLUSION: The CORE-COVID-19 model accurately assigned 88% of patients who potentially progressed to 30-day composite events and revealed improved performance over existing risk scores, indicating its potential utility in clinical practice.

Characteristics, Treatment Patterns, and Clinical Outcomes After Heart Failure Hospitalizations During the COVID-19 Pandemic, March to October 2020.

OBJECTIVE: To compare clinical characteristics, treatment patterns, and 30-day all-cause readmission and mortality between patients hospitalized for heart failure (HF) before and during the coronavirus disease 2019 (COVID-19) pandemic. PATIENTS AND METHODS: The study was conducted at 16 hospitals across 3 geographically dispersed US states. The study included 6769 adults (mean age, 74 years; 56% [5033 of 8989] men) with cumulative 8989 HF hospitalizations: 2341 hospitalizations during the COVID-19 pandemic (March 1 through October 30, 2020) and 6648 in the pre-COVID-19 (October 1, 2018, through February 28, 2020) comparator group. We used Poisson regression, Kaplan-Meier estimates, multivariable logistic, and Cox regression analysis to determine whether prespecified study outcomes varied by time frames. RESULTS: The adjusted 30-day readmission rate decreased from 13.1% (872 of 6648) in the pre-COVID-19 period to 10.0% (234 of 2341) in the COVID-19 pandemic period (relative risk reduction, 23%; hazard ratio, 0.77; 95% CI, 0.66 to 0.89). Conversely, all-cause mortality increased from 9.7% (645 of 6648) in the pre-COVID-19 period to 11.3% (264 of 2341) in the COVID-19 pandemic period (relative risk increase, 16%; number of admissions needed for one additional death, 62.5; hazard ratio, 1.19; 95% CI, 1.02 to 1.39). Despite significant differences in rates of index hospitalization, readmission, and mortality across the study time frames, the disease severity, HF subtypes, and treatment patterns remained unchanged (P>0.05). CONCLUSION: The findings of this large tristate multicenter cohort study of HF hospitalizations suggest lower rates of index hospitalizations and 30-day readmissions but higher incidence of 30-day mortality with broadly similar use of HF medication, surgical interventions, and devices during the COVID-19 pandemic compared with the pre-COVID-19 time frame.

Within-Person Blood Pressure Variability During Hospitalization and Clinical Outcomes Following First-Ever Acute Ischemic Stroke.

BACKGROUND: Uncertainty remains over the relationship between blood pressure (BP) variability (BPV), measured in hospital settings, and clinical outcomes following acute ischemic stroke (AIS). We examined the association between within-person systolic blood pressure (SBP) variability (SBPV) during hospitalization and readmission-free survival, all-cause readmission, or all-cause mortality 1 year after AIS. METHODS: In a cohort of 862 consecutive patients (age [mean ± SD] 75 ± 15 years, 55% women) with AIS (2005-2018, follow-up through 2019), we measured SBPV as quartiles of standard deviations (SD) and coefficient of variation (CV) from a median of 16 SBP readings obtained throughout hospitalization. RESULTS: In the cumulative cohort, the measured SD and CV of SBP in mmHg were 16 ± 6 and 10 ± 5, respectively. The hazard ratios (HR) for readmission-free survival between the highest vs. lowest quartiles were 1.44 (95% confidence interval [CI] 1.04-1.81) for SD and 1.29 (95% CI 0.94-1.78) for CV after adjustment for demographics and comorbidities. Similarly, incident readmission or mortality remained consistent between the highest vs. lowest quartiles of SD and CV (readmission: HR 1.29 [95% CI 0.90-1.78] for SD, HR 1.29 [95% CI 0.94-1.78] for CV; mortality: HR 1.15 [95% CI 0.71-1.87] for SD, HR 0.86 [95% CI 0.55-1.36] for CV). CONCULSIONS: In patients with first AIS, SBPV measured as quartiles of SD or CV based on multiple readings throughout hospitalization has no independent prognostic implications for the readmission-free survival, readmission, or mortality. This underscores the importance of overall patient care rather than a specific focus on BP parameters during hospitalization for AIS.

Plasma Osteopontin Levels and Adverse Cardiovascular Outcomes in the PEACE Trial.

Osteopontin (OPN) is a secreted glycophosphoprotein that has a role in inflammation, immune response and calcification. We hypothesized that plasma OPN levels are associated with adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD) and preserved ejection fraction (EF) enrolled in the PEACE trial. We measured plasma OPN levels at baseline in 3567 CAD patients (mean age 64.5 ± 8.1 years, 81% men) by a sandwich chemiluminescent assay (coefficient of variation = 4.1%). OPN levels were natural log (Ln) transformed prior to analyses. We assessed whether Ln OPN levels were associated with the composite primary endpoint of cardiovascular death, non-fatal myocardial infarction and hospitalization for heart failure using multiple event multivariable Cox proportional hazards regression. Adjustment was performed for: (a) age and sex; (b) additional potential confounders; and (c) a parsimonious set of statistically significant 10 variates. During a median follow-up of 4.8 years, 416 adverse cardiovascular outcomes occurred in 366 patients. Ln OPN was significantly associated with the primary endpoint; HR (95% CI) = 1.56 (1.27, 1.92); P <0.001, and remained significant after adjustment for age and sex [1.31 (1.06, 1.61); P = 0.01] and after adjustment for relevant covariates [1.24 (1.01, 1.52); P = 0.04]. In a secondary analysis of the individual event types, Ln OPN was significantly associated with incident hospitalization for heart failure: HR (95% CI) = 2.04 (1.44, 2.89); P <0.001, even after adjustment for age, sex and additional relevant covariates. In conclusion, in patients with stable CAD and preserved EF on optimal medical therapy, plasma OPN levels were independently associated with the composite incident endpoint of adverse cardiovascular outcomes as well as incident hospitalization for heart failure.

Cardiac troponin in patients hospitalized with acute decompensated heart failure: A systematic review and meta-analysis.

BACKGROUND: Elevated cardiac troponin (cTn) is often observed in patients with acute decompensated heart failure (ADHF). We assessed the magnitude of association and quality of supporting evidence between cTn and clinically important outcomes in persons hospitalized for ADHF. METHODS: We searched MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from inception through February 28, 2015. The outcomes analyzed included hospital length of stay (LOS), readmissions, and mortality. Random effects meta-analysis was used to combine outcomes across studies. RESULTS: We included 26 clinical studies. A detectable or elevated cTn was associated with increased LOS (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.01-1.10), increased in-hospital mortality (OR: 2.57; 95% CI: 2.27-2.91), and a composite of mortality and major adverse events (OR: 1.33; 95% CI: 1.03-1.71) during hospitalization. ADHF patients with a detectable or elevated cTn were at increased risk for mortality and composite of mortality and readmission over the short term (mortality OR: 2.11; 95% CI: 1.43-3.12; composite OR: 2.81; 95% CI: 1.60-4.92), intermediate term (mortality OR: 2.21; 95% CI: 1.46-3.35; composite OR: 2.30; 95% CI: 1.78-2.99), and long term (mortality OR: 3.69; 95% CI: 2.64-5.18; composite OR: 3.49; 95% CI: 2.08-5.84). The overall confidence in estimates was moderate. CONCLUSIONS: Among ADHF patients, a detectable or elevated cTn identifies subjects at increased risk for adverse clinical outcomes during acute hospitalization and those at higher risk for postdischarge mortality and composite of readmission and mortality. Journal of Hospital Medicine 2016;11:446-454. 2016 Society of Hospital Medicine.

A patient-centered approach to the development and pilot of a warfarin pharmacogenomics patient education tool for health professionals.

OBJECTIVE: To describe an exploratory project to develop and pilot a novel patient educational tool that explains the concept of pharmacogenomics and its impact on warfarin dosing that can be utilized by health professionals providing patient counseling. METHODS: A pharmacogenomics educational tool prototype was developed by an interdisciplinary team. During the pilot of the tool, focus group methodology was used to elicit input from patients based upon their perspectives and experiences with warfarin. Focus group sessions were audio-recorded and transcribed, and the data was analyzed through consensus coding in NVivo. RESULTS: The focus group participants were generally unfamiliar with the concept of pharmacogenomics but were receptive to the information. They thought the patient education tool was informative and would provide the most benefit to patients newly initiated on warfarin therapy. CONCLUSIONS: Preliminary results from this exploratory project suggest that implementation and further feasibility testing of this pharmacogenomics patient education tool should be performed in a population of newly initiated patients taking warfarin.

Sex/gender medicine. The biological basis for personalized care in cardiovascular medicine.

Sex differences in morbidity and mortality associated with cardiovascular disease have been recognized by the medical community for decades. Investigation into the underlying biological basis of these differences was largely neglected by the scientific community until a report released by the Institute of Medicine in the United States in 2001 "Exploring the Biological Contributions to Human Health: Does Sex Matter?" Recommendations from this report included the need for more accurate use of the terms "sex" and "gender", better tools and resources to study the biological basis of sex differences, integration of findings from different levels of biological organization and continued synergy between basic and clinical researchers. Ten years after the Institute's report, this review evaluates some of the sex differences in cardiovascular disease, reviews new approaches to study sex differences and emphasizes areas where further research is required. In the era of personalized medicine, the study of the biological basis of sex differences promises to optimize preventive, diagnostic and therapeutic strategies for cardiovascular disease in men and women, but will require diligence by the scientific and medical communities to remember that sex does matter.