A number of studies have reported the association between the use of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) medications and the occurrence or ...severity of coronavirus disease 2019 (COVID-19). Published results are inconclusive, possibly due to differences in participant comorbidities and sociodemographic backgrounds. Since ACEI and ARB are frequently used anti-hypertension medications, we aim to determine whether the use of ACEI and ARB is associated with the occurrence and severity of COVID-19 in a large study of US Veterans with hypertension.
Data were collected from the Department of Veterans Affairs (VA) National Corporate Data Warehouse (VA-COVID-19 Shared Data Resource) between February 28, 2020 and August 18, 2020. Using data from 228,722 Veterans with a history of hypertension who received COVID-19 testing at the VA, we investigated whether the use of ACEI or ARB over the two years prior to the index date was associated with increased odds of (1) a positive COVID-19 test, and (2) a severe outcome (hospitalization, mortality, and use of intensive care unit (ICU) and/or mechanical ventilation) among COVID-19-positive patients. We used logistic regression with and without propensity score weighting (PSW) to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between ACEI/ARB use and a positive COVID-19 test result. The association between medication use and COVID-19 outcome severity was examined using multinomial logistic regression comparing participants who were not hospitalized to participants who were hospitalized, were admitted to the ICU, used a mechanical ventilator, or died. All models were adjusted for relevant covariates, including demographics (age, sex, race, ethnicity), selected comorbidities, and the Charlson Comorbidity Index (CCI).
The use of ACEI significantly decreased the odds of a positive COVID-19 test among Veterans with hypertension (OR = 0.917, (0.887, 0.948) and OR = 0.926, (0.894, 0.958) with PSW). The use of ACEI, but not of ARB, was also associated with significantly increased odds of using mechanical ventilators (OR = 1.265, (1.010, 1.584) and OR = 1.210, (1.053, 1.39) with PSW) among all COVID-19 inpatients compared to outpatients.
In this study of Veterans with hypertension, ACEI was significantly associated with decreased odds of testing positive for COVID-19. With the exception of the association of ACEI with a small non-clinically-important increase in the odds of using mechanical ventilators, neither ACEI nor ARB was found to be associated with clinical severity or mortality among COVID-19-positive Veterans. The results of this study need further corroboration and validation in other cohort samples outside the VA.
Mild cognitive impairment (MCI) is a pre-clinical stage of Alzheimer's disease (AD). Understanding the transition probabilities across the disease continuum of AD, ranging from MCI to AD to Mortality ...is crucial for the economic modeling of AD and effective planning of future interventions and healthcare resource allocation decisions. This study uses the Multi-state Markov model to quantify the transition probabilities along the disease progression and specifically investigates medications as modifiable risk factors of AD associated with accelerated or decelerated transition times from MCI to AD, MCI to mortality, and AD to mortality. Individuals with MCI were identified from the National Alzheimer's Coordinating Center between September 2005 and May 2021. A three-state Markov model was postulated to model the disease progression among three states: MCI, AD, and mortality with adjustment for demographics, genetic characteristics, comorbidities and medications. Transition probabilities, the total length of stay in each state, and the hazard ratios of the use of medications for diabetes, hypertension, and hypercholesterolemia (the known modifiable risk factors of AD) were evaluated for these transitions. 3,324 individuals with MCI were identified. The probability of developing AD after one year since the initial diagnosis of MCI is 14.9%. After approximately 6 years from the initial diagnosis of MCI, the probability of transitioning to AD increases to nearly 41.7% before experiencing a subsequent decline. The expected total lengths of stay were 5.38 (95% CI: 0.002-6.03) years at MCI state and 7.61 (95%CI: 0.002-8.88) years at AD state. Patients with active use of lipid-lowering agents were associated with significantly lower hazards of transitioning from MCI to AD (HR: 0.83, 95%CI:0.71-0.96), MCI to mortality (HR: 0.51, 95%CI:0.34-0.77), and AD to mortality (HR: 0.81, 95%CI:0.66-0.99).
The previously published results of the Systolic Blood Pressure Intervention Trial showed that among participants with hypertension and an increased cardiovascular risk, but without diabetes, the ...rates of cardiovascular events were lower among those who were assigned to a target systolic blood pressure of less than 120 mm Hg (intensive treatment) than among those who were assigned to a target of less than 140 mm Hg (standard treatment). Whether such intensive treatment affected patient-reported outcomes was uncertain; those results from the trial are reported here.
We randomly assigned 9361 participants with hypertension to a systolic blood-pressure target of less than 120 mm Hg or a target of less than 140 mm Hg. Patient-reported outcome measures included the scores on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Veterans RAND 12-Item Health Survey, the Patient Health Questionnaire 9-item depression scale (PHQ-9), patient-reported satisfaction with their blood-pressure care and blood-pressure medications, and adherence to blood-pressure medications. We compared the scores in the intensive-treatment group with those in the standard-treatment group among all participants and among participants stratified according to physical and cognitive function.
Participants who received intensive treatment received an average of one additional antihypertensive medication, and the systolic blood pressure was 14.8 mm Hg (95% confidence interval, 14.3 to 15.4) lower in the group that received intensive treatment than in the group that received standard treatment. Mean PCS, MCS, and PHQ-9 scores were relatively stable over a median of 3 years of follow-up, with no significant differences between the two treatment groups. No significant differences between the treatment groups were noted when participants were stratified according to baseline measures of physical or cognitive function. Satisfaction with blood-pressure care was high in both treatment groups, and we found no significant difference in adherence to blood-pressure medications.
Patient-reported outcomes among participants who received intensive treatment, which targeted a systolic blood pressure of less than 120 mm Hg, were similar to those among participants who received standard treatment, including among participants with decreased physical or cognitive function. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062 .).
Abstract
Background and Objectives
The Veterans RAND 12-Item Health Survey (VR-12) is a generic patient-reported outcome measure of physical and mental health status. An adapted version of the VR-12 ...was developed for use with older adults living in long-term residential care (LTRC) homes in Canada: VR-12 (LTRC-C). This study aimed to evaluate the psychometric validity of the VR-12 (LTRC-C).
Research Design and Methods
Data for this validation study were collected via in-person interviews for a province-wide survey of adults living in LTRC homes across British Columbia (N = 8,657). Three analyses were conducted to evaluate validity and reliability: (1) confirmatory factor analyses were conducted to validate the measurement structure; (2) correlations with measures of depression, social engagement, and daily activities were examined to evaluate convergent and discriminant validity; and (3) Cronbach’s alpha (r) statistics were obtained to evaluate internal consistency reliability.
Results
A measurement model with 2 correlated latent factors (representing physical health and mental health), 4 cross-loadings, and 4 correlated items resulted in an acceptable fit (root-mean-square error of approximation = 0.07; comparative fit index = 0.98). Physical and mental health were correlated in expected directions with measures of depression, social engagement, and daily activities, though the magnitudes of the correlations were quite small. Internal consistency reliability was acceptable for physical and mental health (r > 0.70).
Discussion and Implications
This study supports the use of the VR-12 (LTRC-C) to measure perceived physical and mental health among older adults living in LTRC homes.
Abstract
Determining the sustainability of antibodies targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for predicting immune response against the Coronavirus ...disease 2019 (COVID-19). To quantify the antibody decay rates among the varying levels of anti-nucleocapsid (anti-N) Immunoglobulin G (IgG) in convalescent COVID-19 patients and estimate the length of time they maintained SARS-CoV-2 specific antibodies, we have collected longitudinal blood samples from 943 patients over the course of seven months after their initial detection of SARS-CoV-2 virus by RT-PCR. Anti-N IgG levels were then quantified in these blood samples. The primary study outcome was the comparison of antibody decay rates from convalescent patients with high or low initial levels of antibodies using a mixed linear model. Additional measures include the length of time that patients maintain sustainable levels of anti-N IgG. Antibody quantification of blood samples donated by the same subject multiple times shows a gradual decrease of IgG levels to the cutoff index level of 1.4 signal/cut-off (S/C) on the Abbott Architect SARS-CoV-2 IgG test. In addition, this study shows that antibody reduction rate is dependent on initial IgG levels, and patients with initial IgG levels above 3 S/C show a significant 1.68-fold faster reduction rate compared to those with initial IgG levels below 3 S/C. For a majority of the donors naturally occurring anti-N antibodies were detected above the threshold for only four months after infection with SARS-CoV-2. This study is clinically important for the prediction of immune response capacity in COVID-19 patients.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a multisystem chronic disease estimated to affect 836,000-2.5 million individuals in the United States. Persons with ME/CFS have a ...substantial reduction in their ability to engage in pre-illness levels of activity. Multiple symptoms include profound fatigue, post-exertional malaise, unrefreshing sleep, cognitive impairment, orthostatic intolerance, pain, and other symptoms persisting for more than 6 months. Diagnosis is challenging due to fluctuating and complex symptoms. ME/CFS Common Data Elements (CDEs) were identified in the National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke (NINDS) Common Data Element Repository. This study reviewed ME/CFS CDEs item content. Inclusion criteria for CDEs (measures recommended for ME/CFS) analysis: 1) assesses symptoms; 2) developed for adults; 3) appropriate for patient reported outcome measure (PROM); 4) does not use visual or pictographic responses. Team members independently reviewed CDEs item content using the World Health Organization International Classification of Functioning, Disability and Health (ICF) framework to link meaningful concepts. 119 ME/CFS CDEs (measures) were reviewed and 38 met inclusion criteria, yielding 944 items linked to 1503 ICF meaningful concepts. Most concepts linked to ICF Body Functions component (b-codes; n = 1107, 73.65%) as follows: Fatiguability (n = 220, 14.64%), Energy Level (n = 166, 11.04%), Sleep Functions (n = 137, 9.12%), Emotional Functions (n = 131, 8.72%) and Pain (n = 120, 7.98%). Activities and Participation concepts (d codes) accounted for a smaller percentage of codes (n = 385, 25.62%). Most d codes were linked to the Mobility category (n = 69, 4.59%) and few items linked to Environmental Factors (e codes; n = 11, 0.73%). Relatively few items assess the impact of ME/CFS symptoms on Activities and Participation. Findings support development of ME/CFS-specific PROMs, including items that assess activity limitations and participation restrictions. Development of psychometrically-sound, symptom-based item banks administered as computerized adaptive tests can provide robust assessments to assist primary care providers in the diagnosis and care of patients with ME/CFS.
Statins are a class of medications that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Whether statins can benefit patients with dementia remains unclear because of ...conflicting results. We hypothesized that some of the confusion in the literature might arise from differences in efficacy of different statins. We used a large database to compare the action of several different statins to investigate whether some statins might be differentially associated with a reduction in the incidence of dementia and Parkinson's disease.
We analyzed data from the decision support system of the US Veterans Affairs database, which contains diagnostic, medication and demographic information on 4.5 million subjects. The association of lovastatin, simvastatin and atorvastatin with dementia was examined with Cox proportional hazard models for subjects taking statins compared with subjects taking cardiovascular medications other than statins, after adjusting for covariates associated with dementia or Parkinson's disease.
We observed that simvastatin is associated with a significant reduction in the incidence of dementia in subjects > or =65 years, using any of three models. The first model incorporated adjustment for age, the second model included adjusted for three known risk factors for dementia, hypertension, cardiovascular disease or diabetes, and the third model incorporated adjustment for the Charlson index, which is an index that provides a broad assessment of chronic disease. Data were obtained for over 700,000 subjects taking simvastatin and over 50,000 subjects taking atorvastatin who were aged >64 years. Using model 3, the hazard ratio for incident dementia for simvastatin and atorvastatin are 0.46 (CI 0.44-0.48, p < 0.0001) and 0.91 (CI 0.80-1.02, p = 0.11), respectively. Lovastatin was not associated with a reduction in the incidence of dementia. Simvastatin also exhibited a reduced hazard ratio for newly acquired Parkinson's disease (HR 0.51, CI 0.4-0.55, p < 0.0001).
Simvastatin is associated with a strong reduction in the incidence of dementia and Parkinson's disease, whereas atorvastatin is associated with a modest reduction in incident dementia and Parkinson's disease, which shows only a trend towards significance.
Introduction
Alzheimer's disease (AD) and COVID‐19 share common risk factors including hypertension. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) are ...frequently prescribed antihypertension medications.
Methods
This study analyzed 436,823 veterans tested for SARS‐CoV‐2 infection. We conducted both classical and propensity score weighted logistic models to compare COVID‐19 outcomes between patients with AD or mild cognitive impairment (MCI) to those without cognitive impairment, and examined effect of ACEI/ARB prescription.
Results
There was a statistically significant association between AD and increased odds of infection and mortality. MCI was not found to be a risk factor for infection. Subjects with MCI exhibited poor clinical outcomes. Prescribing ARBs but not ACEIs was significantly associated with a lower risk of COVID‐19 occurrence among AD and MCI patients.
Discussion
Exploring beneficial effects of existing medications to reduce the impact of COVID‐19 on patients with AD or MCI is highly significant.
Highlights
There is significant association between Alzheimer's disease (AD) and increased risk of COVID‐19 infection and odds of mortality.
Subjects with mild cognitive impairment (MCI) defined by claims data exhibit poor clinical outcomes, but MCI was not found to be a risk factor for severe acute respiratory syndrome coronavirus 2 infection.
Prescribing angiotensin II receptor blockers was significantly associated with a lower risk of COVID‐19 occurrence among AD/MCI patients.
In the Systolic Blood Pressure Intervention Trial (SPRINT), adults at high risk for cardiovascular disease who received intensive systolic blood-pressure control (target, <120 mm Hg) had ...significantly lower rates of death and cardiovascular disease events than did those who received standard control (target, <140 mm Hg). On the basis of these data, we wanted to determine the lifetime health benefits and health care costs associated with intensive control versus standard control.
We used a microsimulation model to apply SPRINT treatment effects and health care costs from national sources to a hypothetical cohort of SPRINT-eligible adults. The model projected lifetime costs of treatment and monitoring in patients with hypertension, cardiovascular disease events and subsequent treatment costs, treatment-related risks of serious adverse events and subsequent costs, and quality-adjusted life-years (QALYs) for intensive control versus standard control of systolic blood pressure.
We determined that the mean number of QALYs would be 0.27 higher among patients who received intensive control than among those who received standard control and would cost approximately $47,000 more per QALY gained if there were a reduction in adherence and treatment effects after 5 years; the cost would be approximately $28,000 more per QALY gained if the treatment effects persisted for the remaining lifetime of the patient. Most simulation results indicated that intensive treatment would be cost-effective (51 to 79% below the willingness-to-pay threshold of $50,000 per QALY and 76 to 93% below the threshold of $100,000 per QALY), regardless of whether treatment effects were reduced after 5 years or persisted for the remaining lifetime.
In this simulation study, intensive systolic blood-pressure control prevented cardiovascular disease events and prolonged life and did so at levels below common willingness-to-pay thresholds per QALY, regardless of whether benefits were reduced after 5 years or persisted for the patient's remaining lifetime. (Funded by the National Heart, Lung, and Blood Institute and others; SPRINT ClinicalTrials.gov number, NCT01206062 .).
ObjectiveThis study examined the association of initial provider treatment with early and long-term opioid use in a national sample of patients with new-onset low back pain (LBP).DesignA ...retrospective cohort study of patients with new-onset LBP from 2008 to 2013.SettingThe study evaluated outpatient and inpatient claims from patient visits, pharmacy claims and inpatient and outpatient procedures with initial providers seen for new-onset LBP.Participants216 504 individuals aged 18 years or older across the USA who were diagnosed with new-onset LBP and were opioid-naïve were included. Participants had commercial or Medicare Advantage insurance.ExposuresThe primary independent variable is type of initial healthcare provider including physicians and conservative therapists (physical therapists, chiropractors, acupuncturists).Main outcome measuresShort-term opioid use (within 30 days of the index visit) following new LBP visit and long-term opioid use (starting within 60 days of the index date and either 120 or more days’ supply of opioids over 12 months, or 90 days or more supply of opioids and 10 or more opioid prescriptions over 12 months).ResultsShort-term use of opioids was 22%. Patients who received initial treatment from chiropractors or physical therapists had decreased odds of short-term and long-term opioid use compared with those who received initial treatment from primary care physicians (PCPs) (adjusted OR (AOR) (95% CI) 0.10 (0.09 to 0.10) and 0.15 (0.13 to 0.17), respectively). Compared with PCP visits, initial chiropractic and physical therapy also were associated with decreased odds of long-term opioid use in a propensity score matched sample (AOR (95% CI) 0.21 (0.16 to 0.27) and 0.29 (0.12 to 0.69), respectively).ConclusionsInitial visits to chiropractors or physical therapists is associated with substantially decreased early and long-term use of opioids. Incentivising use of conservative therapists may be a strategy to reduce risks of early and long-term opioid use.
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