Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease

Background: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. Objective: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). Design: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. Setting: Population-based cohort study in Ontario, Canada. Participants: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. Measurements: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. Results: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, −0.01 [95% CI, −0.03 to 0.01]) or men (change in c-statistic, −0.01 [CI, −0.04 to 0.02]). Limitation: Medication use was not available at the population level. Conclusion: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. Primary Funding Source: Canadian Institutes of Health Research.

Testing for Primary Aldosteronism and Mineralocorticoid Receptor Antagonist Use Among U.S. Veterans: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 174, No 3

Background: Primary aldosteronism is a common cause of treatment-resistant hypertension. However, evidence from local health systems suggests low rates of testing for primary aldosteronism. Objective: To evaluate testing rates for primary aldosteronism and evidence-based hypertension management in patients with treatment-resistant hypertension. Design: Retrospective cohort study. Setting: U.S. Veterans Health Administration. Participants: Veterans with apparent treatment-resistant hypertension (n = 269 010) from 2000 to 2017, defined as either 2 blood pressures (BPs) of at least 140 mm Hg (systolic) or 90 mm Hg (diastolic) at least 1 month apart during use of 3 antihypertensive agents (including a diuretic), or hypertension requiring 4 antihypertensive classes. Measurements: Rates of primary aldosteronism testing (plasma aldosterone–renin) and the association of testing with evidence-based treatment using a mineralocorticoid receptor antagonist (MRA) and with longitudinal systolic BP. Results: 4277 (1.6%) patients who were tested for primary aldosteronism were identified. An index visit with a nephrologist (hazard ratio [HR], 2.05 [95% CI, 1.66 to 2.52]) or an endocrinologist (HR, 2.48 [CI, 1.69 to 3.63]) was associated with a higher likelihood of testing compared with primary care. Testing was associated with a 4-fold higher likelihood of initiating MRA therapy (HR, 4.10 [CI, 3.68 to 4.55]) and with better BP control over time. Limitations: Predominantly male cohort, retrospective design, susceptibility of office BPs to misclassification, and lack of confirmatory testing for primary aldosteronism. Conclusion: In a nationally distributed cohort of veterans with apparent treatment-resistant hypertension, testing for primary aldosteronism was rare and was associated with higher rates of evidence-based treatment with MRAs and better longitudinal BP control. The findings reinforce prior observations of low adherence to guideline-recommended practices in smaller health systems and underscore the urgent need for improved management of patients with treatment-resistant hypertension. Primary Funding Source: National Institutes of Health.

Tecovirimat Resistance in an Immunocompromised Patient With Mpox and Prolonged Viral Shedding

COVID-19

COVID-19, the illness caused by SARS-CoV-2, became a worldwide pandemic in 2020. Initial clinical manifestations range from asymptomatic infection to mild upper respiratory illness but may progress to pulmonary involvement with hypoxemia and, in some cases, multiorgan involvement, shock, and death. Older adults, pregnant persons, those with common comorbidities, and those with immunosuppression are at greatest risk for progression. Vaccination is effective in preventing symptomatic infection and reducing risk for severe disease, hospitalization, and death. Antiviral treatment and immunomodulators have been shown to benefit certain patients. This article summarizes current recommendations on prevention, diagnosis, management, and treatment of COVID-19.

The Management of Chronic Insomnia Disorder and Obstructive Sleep Apnea: Synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines

Description: In September 2019, the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients with chronic insomnia disorder and obstructive sleep apnea (OSA). This guideline is intended to give health care teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients with either of these conditions. Methods: In October 2017, the VA/DoD Evidence-Based Practice Work Group initiated a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, created three 1-page algorithms, and advanced 41 recommendations using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Recommendations: This synopsis summarizes the key recommendations of the guideline in 3 areas: diagnosis and assessment of OSA and chronic insomnia disorder, treatment and management of OSA, and treatment and management of chronic insomnia disorder. Three clinical practice algorithms are also included.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C Virus Infection in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2018 Clinical Practice Guideline

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2018 clinical practice guideline for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in chronic kidney disease (CKD) is an extensive update of KDIGO's 2008 guideline on HCV infection in CKD. This update reflects the major advances since the introduction of direct-acting antivirals (DAAs) in the management of HCV infection in the CKD population. Methods: The KDIGO work group tasked with developing the HCV and CKD guideline defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence previously summarized by the evidence review team. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to appraise the quality of evidence and rate the strength of the recommendations. Searches of the English-language literature were conducted through May 2017 and were supplemented with targeted searches for studies of DAA treatment and with abstracts from nephrology, hepatology, and transplantation conferences. A review process involving many stakeholders, subject matter experts, and industry and national organizations informed the guideline's final modification. Recommendation: The updated guideline comprises 66 recommendations. This synopsis focuses on 32 key recommendations pertinent to the prevention, diagnosis, treatment, and management of HCV infection in adult CKD populations.

Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain

Background: Unintentional overdose involving opioid analgesics is a leading cause of injury-related death in the United States. Objective: To evaluate the feasibility and effect of implementing naloxone prescription to patients prescribed opioids for chronic pain. Design: 2-year nonrandomized intervention study. Setting: 6 safety-net primary care clinics in San Francisco, California. Participants: 1985 adults receiving long-term opioid therapy for pain. Intervention: Providers and clinic staff were trained and supported in naloxone prescribing. Measurements: Outcomes were proportion of patients prescribed naloxone, opioid-related emergency department (ED) visits, and prescribed opioid dose based on chart review. Results: 38.2% of 1985 patients receiving long-term opioids were prescribed naloxone. Patients prescribed higher doses of opioids and with an opioid-related ED visit in the past 12 months were independently more likely to be prescribed naloxone. Patients who received a naloxone prescription had 47% fewer opioid-related ED visits per month in the 6 months after receipt of the prescription (incidence rate ratio [IRR], 0.53 [95% CI, 0.34 to 0.83]; P  = 0.005) and 63% fewer visits after 1 year (IRR, 0.37 [CI, 0.22 to 0.64]; P < 0.001) compared with patients who did not receive naloxone. There was no net change over time in opioid dose among those who received naloxone and those who did not (IRR, 1.03 [CI, 0.91 to 1.27]; P = 0.61). Limitation: Results are observational and may not be generalizable beyond safety-net settings. Conclusion: Naloxone can be coprescribed to primary care patients prescribed opioids for pain. When advised to offer naloxone to all patients receiving opioids, providers may prioritize those with established risk factors. Providing naloxone in primary care settings may have ancillary benefits, such as reducing opioid-related adverse events. Primary Funding Source: National Institutes of Health.

Cardiology: What You May Have Missed in 2023

Cardiology and all its subspecialties continue to push the envelope in developing new treatment strategies for a wide variety of diseases. After screening more than 1300 articles, we highlight a selection of important cardiology articles published in 2023. Starting with prevention, we note articles that look at the effect of semaglutide in patients with obesity as well as a first-in-class drug, bempedoic acid, on cardiovascular outcomes. We have also examined new evidence comparing conservative management with invasive management of frail, older patients with non–ST-segment elevation myocardial infarction (NSTEMI). In patients with cardiac arrest secondary to NSTEMI, another article examines the rationale for expedited transfer to a cardiac arrest center. The STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) trial builds on looking at half-dose thrombolysis in older populations with STEMI. Emphasis is placed on guideline-directed medical therapy before hospital discharge in those with heart failure. In addition, in patients with stable symptomatic coronary artery disease, initial noninvasive testing using coronary computed tomography angiography may be a viable option compared with invasive strategies. More details have emerged on anticoagulation strategies in those with device-detected atrial fibrillation. Finally, transcatheter approaches to treat both mitral and tricuspid regurgitation have also been included.

Video Teleconferencing for Disease Prevention, Diagnosis, and Treatment: A Rapid Review: Annals of Internal Medicine: Vol 175, No 2

Background: Video teleconferencing (VTC) as a substitute for in-person health care or as an adjunct to usual care has increased in recent years. Purpose: To assess the benefits and harms of VTC visits for disease prevention, diagnosis, and treatment and to develop an evidence map describing gaps in the evidence. Data Sources: Systematically searched PubMed, EMBASE, Web of Science, and the Cochrane Library from 1 January 2013 to 3 March 2021. Study Selection: Two investigators independently screened the literature and identified 38 randomized controlled trials (RCTs) meeting inclusion criteria. Data Extraction: Data abstraction by a single investigator was confirmed by a second investigator; 2 investigators independently rated risk of bias. Data Synthesis: Results from 20 RCTs rated low risk of bias or some concerns of bias show that the use of VTC for the treatment and management of specific diseases produces largely similar outcomes when used to replace or augment usual care. Nine of 12 studies where VTC was intended to replace usual care and 5 of 8 studies where VTC was intended to augment usual care found similar effects between the intervention and control groups. The remaining 6 included studies (3 intended to replace usual care and 3 intended to augment usual care) found 1 or more primary outcomes that favored the VTC group over the usual care group. Studies comparing VTC with usual care that did not involve in-person care were more likely to favor the VTC group. No studies evaluated the use of VTC for diagnosis or prevention of disease. Studies that reported harms found no differences between the intervention and control groups; however, many studies did not report harms. No studies evaluated the effect of VTC on health equity or disparities. Limitations: Studies that focused on mental health, substance use disorders, maternal care, and weight management were excluded. Included studies were limited to RCTs with sample sizes of 50 patients or greater. Component analyses were not conducted in the studies. Conclusion: Replacing or augmenting aspects of usual care with VTC generally results in similar clinical effectiveness, health care use, patient satisfaction, and quality of life as usual care for areas studied. However, included trials were limited to a handful of disease categories, with patients seeking care for a limited set of purposes. Primary Funding Source: Patient-Centered Outcomes Research Institute.

Defining, Estimating, and Communicating Overdiagnosis in Cancer Screening

The toll of inadequate health care is well-substantiated, but recognition is mounting that “too much” is also possible. Overdiagnosis represents one harm of too much medicine, but the concept can be confusing: It is often conflated with related harms (such as overtreatment, misclassification, false-positive results, and overdetection) and is difficult to measure because it cannot be directly observed. Because the U.S. Preventive Services Task Force (USPSTF) issues screening recommendations aimed largely at healthy persons, it has a particular interest in understanding harms related to screening, especially but not limited to overdiagnosis. In support of the USPSTF, the authors summarize the knowledge and provide guidance on defining, estimating, and communicating overdiagnosis in cancer screening. To improve consistency, thinking, and reporting about overdiagnosis, they suggest a specific definition. The authors articulate how variation in estimates of overdiagnosis can arise, identify approaches to estimating overdiagnosis, and describe best practices for communicating the potential for harm due to overdiagnosis.