Incidence and prognostic significance of newly-diagnosed atrial fibrillation among older U.S. veterans hospitalized with COVID-19.

Most prior studies on the prognostic significance of newly-diagnosed atrial fibrillation (AF) in COVID-19 did not differentiate newly-diagnosed AF from pre-existing AF. To determine the association between newly-diagnosed AF and in-hospital and 30-day mortality among regular users of Veterans Health Administration using data linked to Medicare. We identified Veterans aged ≥ 65 years who were hospitalized for ≥ 24 h with COVID-19 from 06/01/2020 to 1/31/2022 and had ≥ 2 primary care visits within 24 months prior to the index hospitalization. We performed multivariable logistic regression analyses to estimate adjusted risks, risk differences (RD), and odds ratios (OR) for the association between newly-diagnosed AF and the mortality outcomes adjusting for patient demographics, baseline comorbidities, and presence of acute organ dysfunction on admission. Of 23,299 patients in the study cohort, 5.3% had newly-diagnosed AF, and 29.2% had pre-existing AF. In newly-diagnosed AF adjusted in-hospital and 30-day mortality were 16.5% and 22.7%, respectively. Newly-diagnosed AF was associated with increased mortality compared to pre-existing AF (in-hospital: OR 2.02, 95% confidence interval [CI] 1.72-2.37; RD 7.58%, 95% CI 5.54-9.62) (30-day: OR 1.86; 95% CI 1.60-2.16; RD 9.04%, 95% CI 6.61-11.5) or no AF (in-hospital: OR 2.24, 95% CI 1.93-2.60; RD 8.40%, 95% CI 6.44-10.4) (30-day: 2.07, 95% CI 1.80-2.37; RD 10.2%, 95% CI 7.89-12.6). There was a smaller association between pre-existing AF and the mortality outcomes. Newly-diagnosed AF is an important prognostic marker for patients hospitalized with COVID-19. Whether prevention or treatment of AF improves clinical outcomes in these patients remains unknown.

Predictive value of ASCVD risk score for mortality and major adverse cardiovascular events in the year following a COVID-19 infection among US Veterans.

BACKGROUND: Morbidity and mortality following COVID-19 infection may be influenced by baseline atherosclerotic cardiovascular disease (ASCVD) risk, yet limited data are available to identify those at highest risk. We examined the association between baseline ASCVD risk with mortality and major adverse cardiovascular events (MACE) in the year following COVID-19 infection. METHODS: We evaluated a nationwide retrospective cohort of US Veterans free of ASCVD who were tested for COVID-19. The primary outcome was absolute risk of all-cause mortality in the year following a COVID-19 test among those hospitalized vs. not stratified by baseline VA-ASCVD risk scores. Secondarily, risk of MACE was examined. RESULTS: There were 393,683 Veterans tested for COVID-19 and 72,840 tested positive. Mean age was 57 years, 86% were male, and 68% were white. Within 30 days following infection, hospitalized Veterans with VA-ASCVD scores >20% had an absolute risk of death of 24.6% vs. 9.7% (P ≤0.0001) for those who tested positive and negative for COVID-19 respectively. In the year following infection, risk of mortality attenuated with no difference in risk after 60 days. The absolute risk of MACE was similar for Veterans who tested positive or negative for COVID-19. CONCLUSIONS: Veterans without clinical ASCVD experienced an increased absolute risk of death within 30 days of a COVID-19 infection compared to Veterans with the same VA-ASCVD risk score who tested negative, but this risk attenuated after 60 days. Whether cardiovascular preventive medications can lower the risk of mortality and MACE in the acute period following COVID-19 infection should be evaluated.

Racial and Ethnic Differences in Short- and Long-term Mortality by Stroke Type.

BACKGROUND AND OBJECTIVES: Racial and ethnic disparities in stroke outcomes exist, however differences by stroke type are less understood. We studied the association of race and ethnicity with stroke mortality, by stroke type, in a national sample of hospitalized patients in the Veterans Health Administration. METHODS: A retrospective observational study was performed including non-Hispanic White, non-Hispanic Black, and Hispanic patients with a first hospitalization for stroke between 2002 and 2012. Stroke was determined using International Classification of Diseases-Ninth Revision codes, and date of death was obtained from the National Death Index. For each of acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), we constructed a piecewise multivariable model for all-cause mortality, using follow-up intervals of ≤30 days, 31-90 days, 91 days-1 year, and >1 year. RESULTS: Among 37,790 stroke patients (89% AIS, 9% ICH, 2% SAH), 25,492 (67%) were non-Hispanic White, 9,752 (26%) were non-Hispanic Black, and 2,546 (7%) were Hispanic. The cohort was predominantly male (98%). Compared to White patients, Black patients experienced better 30-day survival after AIS (HR=0.80, 95% CI 0.73-0.88; 1.4% risk difference) and worse 30-day survival after ICH (HR=1.24, 95% CI 1.06-1.44; 3.2% risk difference). Hispanic patients experienced reduced risk for >1-year mortality after AIS (HR=0.87, 95% CI 0.80-0.94), but had greater risk of 30-day mortality after SAH compared to White patients (HR=1.61, 95% CI 1.03-2.52; 10.3% risk difference). DISCUSSION: In our study, absolute risk of 30-day mortality after ICH was 3.2% higher for Black patients and after SAH was 10.3% higher for Hispanic patients, compared to White patients. These findings underscore the importance of investigating stroke outcomes by stroke type, to better understand the factors driving observed racial and ethnic disparities.

Prediction of Cardiovascular and All-Cause Mortality After Myocardial Infarction in US Veterans.

Risk prediction models for cardiovascular disease (CVD) death developed from patients without vascular disease may not be suitable for myocardial infarction (MI) survivors. Prediction of mortality risk after MI may help to guide secondary prevention. Using national electronic record data from the Veterans Health Administration 2002 to 2012, we developed risk prediction models for CVD death and all-cause death based on 5-year follow-up data of 100,601 survivors of MI using Cox proportional hazards models. Model performance was evaluated using a cross-validation approach. During follow-up, there were 31,622 deaths and 12,901 CVD deaths. In men, older age, current smoking, atrial fibrillation, heart failure, peripheral artery disease, and lower body mass index were associated with greater risk of death from CVD or all-causes, and statin treatment, hypertension medication, estimated glomerular filtration rate level, and high body mass index were significantly associated with reduced risk of fatal outcomes. Similar associations and slightly different predictors were observed in women. The estimated Harrell's C-statistics of the final model versus the cross-validation estimates were 0.77 versus 0.77 in men and 0.81 versus 0.77 in women for CVD death. Similarly, the C-statistics were 0.75 versus 0.75 in men, 0.78 versus 0.75 in women for all-cause mortality. The predicted risk of death was well calibrated compared with the observed risk. In conclusion, we developed and internally validated risk prediction models of 5-year risk for CVD and all-cause death for outpatient survivors of MI. Traditional risk factors, co-morbidities, and lack of blood pressure or lipid treatment were all associated with greater risk of CVD and all-cause mortality.

Low Blood Pressure, Comorbidities, and Ischemic Stroke Mortality in US Veterans.

BACKGROUND AND PURPOSE: Low blood pressure (BP) is associated with higher stroke mortality, although the factors underlying this association have not been fully explored. We investigated prestroke BP and long-term mortality after ischemic stroke in a national sample of US veterans. METHODS: Using a retrospective cohort study design of veterans hospitalized between 2002 and 2007 with a first ischemic stroke and with ≥1 outpatient BP measurements 1 to 18 months before admission, we defined 6 categories each of average prestroke systolic BP (SBP) and diastolic BP, and 7 categories of pulse pressure. Patients were followed-up to 12 years for primary outcomes of all-cause and cardiovascular mortality. We used Cox models to relate prestroke BP indices to mortality and stratified analyses by the presence of preexisting comorbidities (smoking, myocardial infarction, heart failure, atrial fibrillation/flutter, cancer, and dementia), race and ethnicity. RESULTS: Of 29 690 eligible veterans with stroke (mean±SD age 67±12 years, 98% men, 67% White), 2989 (10%) had average prestroke SBP<120 mm Hg. During a follow-up of 4.1±3.3 years, patients with SBP<120 mm Hg experienced 61% all-cause and 27% cardiovascular mortality. In multivariable analyses, patients with the lowest SBP, lowest diastolic BP, and highest pulse pressure had the highest mortality risk: SBP<120 versus 130 to 139 mm Hg (hazard ratio=1.26 [95% CI, 1.19-1.34]); diastolic BP <60 versus 70 to 79 mm Hg (hazard ratio=1.35 [95% CI, 1.23-1.49]); and pulse pressure ≥90 versus 60 to 69 mm Hg (hazard ratio=1.24 [95% CI, 1.15-1.35]). Patients with average SBP<120 mm Hg and at least one comorbidity (smoking, heart disease, cancer, or dementia) had the highest mortality risk (hazard ratio=1.45 [95% CI, 1.37-1.53]). CONCLUSIONS: Compared with normotension, low prestroke BP was associated with mortality after stroke, particularly among patients with at least one comorbidity.

Estimation of Atherosclerotic Cardiovascular Disease Risk Among Patients in the Veterans Affairs Health Care System.

Importance: Current guidelines recommend statin therapy for millions of US residents for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). It is unclear whether traditional prediction models that do not account for current widespread statin use are sufficient for risk assessment. Objectives: To examine the performance of the Pooled Cohort Equations (PCE) for 5-year ASCVD risk estimation in a contemporary cohort and to test the hypothesis that inclusion of statin therapy improves model performance. Design, Setting, and Participants: This cohort study included adult patients in the Veterans Affairs health care system without baseline ASCVD. Using national electronic health record data, 3 Cox proportional hazards models were developed to estimate 5-year ASCVD risk, as follows: the variables and published ß coefficients from the PCE (model 1), the PCE variables with cohort-derived ß coefficients (model 2), and model 2 plus baseline statin use (model 3). Data were collected from January 2002 to December 2012 and analyzed from June 2016 to March 2020. Exposures: Traditional ASCVD risk factors from the PCE plus baseline statin use. Main Outcomes and Measures: Incident ASCVD and ASCVD mortality. Results: Of 1 672 336 patients in the cohort (mean [SD] baseline age 58.0 [13.8] years, 1 575 163 [94.2%] men, 1 383 993 [82.8%] white), 312 155 (18.7%) were receiving statin therapy at baseline. During 5 years of follow-up, 66 605 (4.0%) experienced an ASCVD event, and 31 878 (1.9%) experienced ASCVD death. Compared with the original PCE, the cohort-derived model did not improve model discrimination in any of the 4 age-sex strata but did improve model calibration. The PCE overestimated ASCVD risk compared with the cohort-derived model; 211 237 of 1 136 161 white men (18.6%), 29 634 of 218 463 black men (13.6%), 1741 of 44 399 white women (3.9%), and 836 of 16 034 black women (5.2%) would be potentially eligible for statin therapy under the PCE but not the cohort-derived model. When added to the cohort-derived model, baseline statin therapy was associated with a 7% (95% CI, 5%-9%) lower relative risk of ASCVD and a 25% (95% CI, 23%-28%) lower relative risk for ASCVD death. Conclusions and Relevance: In this study, lower than expected rates of incident ASCVD events in a contemporary national cohort were observed. The PCE overestimated ASCVD risk, and more than 15% of patients would be potentially eligible for statin therapy based on the PCE but not on a cohort-derived model. In the statin era, health care professionals and systems should base ASCVD risk assessment on models calibrated to their patient populations.

Memantine in the Treatment of Executive Function Deficits in Adults With ADHD.

OBJECTIVE: To evaluate the efficacy and safety of memantine hydrochloride as an adjunct to stimulant pharmacotherapy for treating executive function deficits (EFDs) in adults with ADHD. METHOD: This was a 12-week, double-blind, placebo-controlled, randomized clinical trial of memantine added to open-label treatment with stimulant medication. Because of the small sample size, we considered a standardized mean difference (equivalent to effect size) of ≥0.5 and odds ratios ≥2 as indicators of trend improvements. RESULTS: Twelve participants received memantine and 14 received a placebo. Trend improvements favoring memantine were observed on Behavior Rating Inventory of Executive Functions-Adult Inhibition and Self-Monitor subscales when compared with Placebo. No significant changes were noted on the Cambridge Neuropsychological Test Automated Battery. CONCLUSION: Among adults with ADHD and EFDs, adjunct treatment with memantine to osmotic release oral system-methylphenidate (OROS-MPH) was associated with improvements in selective areas of executive functioning, supporting the need for further research.

Symptom Profile of ADHD in Youth With High-Functioning Autism Spectrum Disorder: A Comparative Study in Psychiatrically Referred Populations.

OBJECTIVE: To compare the clinical presentation of ADHD between youth with autism spectrum disorder (ASD) and ADHD and a sample of youth with ADHD only. METHOD: A psychiatrically referred sample of autism spectrum disorder (ASD) youth with ADHD attending a specialized ambulatory program for ASD ( n = 107) and a sample of youth with ADHD attending a general child psychiatry ambulatory clinic ( n = 74) were compared. RESULTS: Seventy-six percent of youth with ASD met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ADHD. The clinical presentation of ADHD in youth with ASD was predominantly similar to its typical presentation including age at onset (3.5 ± 1.7 vs. 4.0 ± 1.9; p = .12), distribution of diagnostic subtypes, the qualitative and quantitative symptom profile, and symptom severity. Combined subtype was the most frequent presentation of ADHD in ASD youth. CONCLUSION: Despite the robust presentation of ADHD, a significant majority of ASD youth with ADHD failed to receive appropriate ADHD treatment (41% vs. 24%; p = .02). A high rate of comorbidity with ADHD was observed in psychiatrically referred youth with ASD, with a clinical presentation typical of the disorder.

Correction: A Randomized Clinical Trial of High Eicosapentaenoic Acid Omega-3 Fatty Acids and Inositol as Monotherapy and in Combination in the Treatment of Pediatric Bipolar Spectrum Disorders: A Pilot Study.

This corrects the article DOI: 10.4088/JCP.14m09267.

Long-term Natural History of Dry Eye Disease from the Patient's Perspective.

PURPOSE: To describe the natural history of dry eye disease (DED), which chronically affects millions of people in the United States. DESIGN: This study is based on the Women's Health Study and Physicians' Health Studies, and uses questionnaires and medical records. PARTICIPANTS: A total of 398 men and 386 women who reported a diagnosis of DED and responded to a questionnaire about change in disease since diagnosis. METHODS: Three subscales were developed using factor analysis of questionnaire responses: ocular surface symptoms, vision-related symptoms, and social impact. We examined correlates of worsening on each subscale, obtained medical records from a subset of 261 study participants, and examined changes in clinical signs of DED over time. MAIN OUTCOME MEASURES: Worsening in ocular surface symptoms, vision-related symptoms, and social impact plus clinical signs. RESULTS: The average duration of DED of 10.5 years (standard deviation, 9.5 years). Worsening was reported by 24% for ocular surface symptoms, 29% for vision-related symptoms, and 10% for social impact. Factors associated with worsening on at least 2 of 3 subscales included a previous report of severe DED symptoms (odds ratio [OR], 2.17 for ocular surface symptoms; OR, 2.35 for vision-related symptoms), spending >$20 per month on DED treatments (OR, 1.80 for ocular surface symptoms; OR, 1.99 for vision-related symptoms), history of blepharitis or meibomian gland dysfunction (MGD) (OR, 1.57 for vision-related symptoms; OR, 2.12 for social impact), and use of systemic beta-blockers (OR, 1.62 for ocular surface symptoms; OR, 1.84 for vision-related symptoms; OR, 1.86 for the social impact of DED). Presence of corneal staining based on review of medical records was associated with use of level 2 or higher DED treatments (OR, 1.54; confidence interval [CI], 1.01-2.36), a previous report of severe DED symptoms (OR, 1.79; CI, 1.07-3.00), having a tear break-up test performed (OR, 2.73; CI, 1.72-4.36), and having blepharitis or MGD (OR, 0.59; CI, 0.35-0.98). CONCLUSIONS: A proportion of patients with DED experience worsening over time, tending to report with more severe symptoms earlier in the disease. Forthcoming data on the natural history of DED from prospective studies should help clarify some of the limitations of this retrospective study.

A randomized clinical trial of high eicosapentaenoic acid omega-3 fatty acids and inositol as monotherapy and in combination in the treatment of pediatric bipolar spectrum disorders: a pilot study.

OBJECTIVE: We conducted a 12-week, randomized, double-blind, controlled clinical trial to evaluate the effectiveness and tolerability of high eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) omega-3 fatty acids and inositol as monotherapy and in combination in children with bipolar spectrum disorders. METHOD: Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms. Subjects with severe illness were excluded. Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol. Data were collected from February 2012 to November 2013. RESULTS: Twenty-four subjects were exposed to treatment (≥ 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n =10]). Fifty-four percent of the subjects completed the study. Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05). Similar results were found for the Children's Depression Rating Scale (P < .05) and the Brief Psychiatric Rating Scale (P <.05). CONCLUSION: Results of this pilot randomized, double-blind, controlled trial suggest that the combined treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders. Results should be interpreted in light of limitations, which include exclusion of severely ill subjects, 54% completion rate, and small sample size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01396486.

Attention-deficit/hyperactivity disorder and adverse health outcomes in adults.

Whereas the adverse impact of attention-deficit/hyperactivity disorder (ADHD) on emotional and psychosocial well-being has been well investigated, its impact on physical health has not. The main aim of this study was to assess the impact of ADHD on lifestyle behaviors and measures of adverse health risk indicators. Subjects were 100 untreated adults with ADHD and 100 adults without ADHD of similar age and sex. Unhealthy lifestyle indicators included assessments of bad health habits, frequency of visits to healthcare providers, and follow through with recommended prophylactic tests. Assessments of adverse health risk indicators included measurements of cardiovascular and metabolic parameters, weight, body mass index, and waist circumference. No differences were identified in health habits between subjects with and without ADHD, but robust differences were found in a wide range of adverse health risk indicators. ADHD is associated with an adverse impact in health risk indicators well known to be associated with high morbidity and mortality.

Re-examining the risk for switch from unipolar to bipolar major depressive disorder in youth with ADHD: a long term prospective longitudinal controlled study.

BACKGROUND: Recent studies have identified subthreshold forms of bipolar (BP)-I disorder and deficits in emotional regulation as risk factors for bipolar disorder in youth. The primary aim of this study was to investigate whether emotional dysregulation and subthreshold forms of BP-I disorder increase the risk for BP switches in ADHD youth with non-bipolar MDD. METHODS: We used data from two large controlled longitudinal family studies of boys and girls with and without ADHD. Subjects (N=522) were followed prospectively and blindly over an average follow up period of 11.4 years. Comparisons were made between ADHD youth with unipolar major depression (MDD) who did (N=24) and did not (N=79) switch to BP-I disorder at follow-up. RESULTS: The rate of conversion to BP-I disorder at follow up was higher in MDD subjects with subthreshold BP-I disorder at baseline compared to those without (57% vs. 21%; OR=9.57, 95% CI=1.62-56.56, p=0.013) and in MDD subjects with deficient emotional self-regulation (OR=3.54, 95% CI=1.08-11.60, p=0.037). LIMITATIONS: The sample was largely Caucasian, so these results may not generalize to minority groups. The sample of youth with SED was small, which limited the statistical power for some analyses. CONCLUSIONS: Switches from unipolar MDD to BP-I disorder in children with ADHD and MDD were predicted by baseline subthreshold BP-I disorder symptoms and baseline deficits in emotional regulation. More work is needed to assess whether these risk factors are operant outside the context of ADHD.