The Management of Substance Use Disorders: Synopsis of the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Description: In August 2021, leadership within the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of substance use disorders (SUDs). This synopsis summarizes key recommendations. Methods: In March 2020, the VA/DoD Evidence-Based Practice Work Group assembled a team to update the 2015 VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 35 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis presents the recommendations that were believed to be the most clinically impactful. Recommendations: The scope of the CPG is broad; however, this synopsis focuses on key recommendations for the management of alcohol use disorder, use of buprenorphine in opioid use disorder, contingency management, and use of technology and telehealth to manage patients remotely.

Stigma

Impact of Hepatitis C Treatment Uptake on Cirrhosis and Mortality in Persons Who Inject Drugs: A Longitudinal, Community-Based Cohort Study: Annals of Internal Medicine: Vol 175, No 8

Background: Hepatitis C virus (HCV) infection can be cured, and the United States has joined the World Health Organization in calling for HCV elimination by 2030. However, historically low uptake of HCV treatment among people who inject drugs (PWID) threatens HCV elimination and exacerbates social and racial health disparities. Objective: To assess whether all-oral HCV treatments were accessed by PWID and reduced liver disease burden and mortality. Design: Community-based, longitudinal cohort study of persons with a history of injection drug use. Setting: Baltimore, Maryland. Participants: 1323 participants enrolled in the ALIVE (AIDS Linked to the IntraVenous Experience) study from 2006 to 2019 and chronically infected with HCV. Measurements: Liver stiffness measures (LSMs) by transient elastography, HCV RNA, and mortality from the National Death Index. Results: Among 1323 persons with evidence of chronic HCV infection at baseline, the median age was 49 years. Most were Black (82%), male (71%), and HIV-negative (66%). The proportion in whom HCV RNA was detected decreased from 100% (by definition) in 2006 to 48% in 2019. Across 10 350 valid LSMs, cirrhosis was detected in 15% of participants in 2006, 19% in 2015, and 8% in 2019. Undetectable HCV RNA was significantly associated with reduced odds of cirrhosis (adjusted odds ratio, 0.28 [95% CI, 0.17 to 0.45]) and reduced all-cause mortality risk (adjusted hazard ratio, 0.54 [CI, 0.38 to 0.77]). Limitation: Noninvasive markers of liver fibrosis have not been validated in persons with sustained virologic response. Conclusion: Many community-based PWID in Baltimore are receiving HCV treatment, which is associated with sharp decreases in liver disease and mortality. Additional efforts will be needed to reduce residual barriers to treatment and to eliminate HCV as a public health threat for PWID. Primary Funding Source: National Institutes of Health.

Reversing the Tide of Racial and Ethnic Disparities in Excess Deaths During the COVID-19 Pandemic

Historically High Excess Mortality During the COVID-19 Pandemic in Switzerland, Sweden, and Spain

Background: Excess mortality quantifies the overall mortality impact of a pandemic. Mortality data have been accessible for many countries in recent decades, but few continuous data have been available for longer periods. Objective: To assess the historical dimension of the COVID-19 pandemic in 2020 for 3 countries with reliable death count data over an uninterrupted span of more than 100 years. Design: Observational study. Setting: Switzerland, Sweden, and Spain, which were militarily neutral and not involved in combat during either world war and have not been affected by significant changes in their territory since the end of the 19th century. Participants: Complete populations of these 3 countries. Measurements: Continuous series of recorded deaths (from all causes) by month from the earliest available year (1877 for Switzerland, 1851 for Sweden, and 1908 for Spain) were jointly modeled with annual age group–specific death and total population counts using negative binomial and multinomial models, which accounted for temporal trends and seasonal variability of prepandemic years. The aim was to estimate the expected number of deaths in a pandemic year for a nonpandemic scenario and the difference in observed and expected deaths aggregated over the year. Results: In 2020, the number of excess deaths recorded per 100 000 persons was 100 (95% credible interval [CrI], 60 to 135) for Switzerland, 75 (CrI, 40 to 105) for Sweden, and 155 (CrI, 110 to 195) for Spain. In 1918, excess mortality was 6 to 7 times higher. In all 3 countries, the peaks of monthly excess mortality in 2020 were greater than most monthly excess mortality since 1918, including many peaks due to seasonal influenza and heat waves during that period. Limitation: Historical vital statistics might be affected by minor completeness issues before the beginning of the 20th century. Conclusion: In 2020, the COVID-19 pandemic led to the second-largest infection-related mortality disaster in Switzerland, Sweden, and Spain since the beginning of the 20th century. Primary Funding Source: Foundation for Research in Science and the Humanities at the University of Zurich, Swiss National Science Foundation, and National Institute of Allergy and Infectious Diseases.

Human Papillomavirus Vaccine Impact and Effectiveness Through 12 Years After Vaccine Introduction in the United States, 2003 to 2018

Background: Human papillomavirus (HPV) vaccination was introduced in 2006 for females and in 2011 for males. Objective: To estimate vaccine impact and effectiveness against quadrivalent HPV vaccine (4vHPV)–type prevalent infection among sexually experienced U.S. females and vaccine effectiveness for sexually experienced U.S. males. Design: NHANES (National Health and Nutrition Examination Survey) conducted in 2003 to 2006 (prevaccine era) and in 2007 to 2010, 2011 to 2014, and 2015 to 2018 (vaccine eras). Setting: Nationally representative U.S. surveys. Participants: Sexually experienced participants aged 14 to 24 years. Intervention: U.S. HPV vaccination program. Measurements: Participant-collected cervicovaginal and penile specimens were tested for HPV DNA. The prevalences of 4vHPV and non-4vHPV types were estimated in each era for females and in 2013 to 2016 for males. Prevalences among the female population overall, vaccinated females, and unvaccinated females were compared in vaccine eras versus the prevaccine era (vaccine impact). Within each vaccine era, prevalence among vaccinated females was compared with that among unvaccinated females (vaccine effectiveness). Vaccine impact and effectiveness were estimated as (1 − prevalence ratio) · 100. Results: Among sexually experienced females aged 14 to 24 years, the impact on 4vHPV-type prevalence in 2015 to 2018 was 85% overall, 90% among vaccinated females, and 74% among unvaccinated females. No significant declines were found in non–4vHPV-type prevalence. Vaccine effectiveness ranged from 60% to 84% during vaccine eras for females and was 51% during 2013 to 2016 for males. Limitation: Self- or parent-reported vaccination history and small numbers in certain subgroups limited precision. Conclusion: Nationally representative data show increasing impact of the vaccination program and herd protection. Vaccine effectiveness estimates will be increasingly affected by herd effects. Primary Funding Source: Centers for Disease Control and Prevention.

Data: The Lifeblood of the Public Health Response to COVID-19

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.

Adverse Events Associated With Coprescription of Phosphodiesterase Type 5 Inhibitors and Oral Organic Nitrates in Male Patients With Ischemic Heart Disease: A Case-Crossover Study: Annals of Internal Medicine: Vol 175, No 6

Background: Concomitant use of oral organic nitrates (nitrates) and phosphodiesterase type 5 (PDE5) inhibitors is contraindicated. Objective: To measure temporal trends in the coprescription of nitrates and PDE5 inhibitors and to measure the association between cardiovascular outcomes and the coprescription of nitrates with PDE5 inhibitors. Design: Case-crossover design. Setting: Nationwide study of Danish patients from 2000 to 2018. Patients: Male patients with International Classification of Diseases, 10th Revision (ICD-10) codes for ischemic heart disease (IHD), including those who had a continuing prescription for nitrates and a new, filled prescription for PDE5 inhibitors. Measurements: Two composite outcomes were measured: 1) cardiac arrest, shock, myocardial infarction, ischemic stroke, or acute coronary arteriography and 2) syncope, angina pectoris, or drug-related adverse event. Results: From 2000 to 2018, 249 541 male patients with IHD were identified. Of these, 42 073 patients had continuing prescriptions for nitrates. During this period, the prescription rate for PDE5 inhibitors in patients with IHD who were taking nitrates increased from an average of 0.9 prescriptions (95% CI, 0.5 to 1.2 prescriptions) per 100 persons per year in 2000 to 19.5 prescriptions (CI, 18.0 to 21.1 prescriptions) in 2018. No statistically significant association was found between the coprescription of nitrates with PDE5 inhibitors and the risk for either composite outcome (odds ratio [OR], 0.58 [CI, 0.28 to 1.13] for the first outcome and OR, 0.73 [CI, 0.40 to 1.32] for the second outcome). Limitation: An assumption was made that concurrently filled prescriptions for nitrates and PDE5 inhibitors equaled concomitant use. Conclusion: From 2000 to 2018, the use of PDE5 inhibitors increased 20-fold among Danish patients with IHD who were taking nitrates. A statistically significant association between concomitant use of these medications and cardiovascular adverse events could not be identified. Primary Funding Source: Ib Mogens Kristiansens Almene Fond and Helsefonden.

Vitamin D Deficiency Increases Mortality Risk in the UK Biobank: A Nonlinear Mendelian Randomization Study: Annals of Internal Medicine: Vol 175, No 11

Background: Low vitamin D status is associated with increased mortality, but randomized trials on severely deficient participants are lacking. Objective: To assess genetic evidence for the causal role of low vitamin D status in mortality. Design: Nonlinear Mendelian randomization analyses. Setting: UK Biobank, a large-scale, prospective cohort from England, Scotland, and Wales with participants recruited between March 2006 and July 2010. Participants: 307 601 unrelated UK Biobank participants of White European ancestry (aged 37 to 73 years at recruitment) with available measurements of 25-hydroxyvitamin D (25-(OH)D) and genetic data. Measurements: Genetically predicted 25-(OH)D was estimated using 35 confirmed variants of 25-(OH)D. All-cause and cause-specific mortality (cardiovascular disease [CVD], cancer, and respiratory) were recorded up to June 2020. Results: There were 18 700 deaths during the 14 years of follow-up. The association of genetically predicted 25-(OH)D with all-cause mortality was L-shaped (P for nonlinearity < 0.001), and risk for death decreased steeply with increasing concentrations until 50 nmol/L. Evidence for an association was also seen in analyses of mortality from cancer, CVD, and respiratory diseases (P ≤ 0.033 for all outcomes). Odds of all-cause mortality in the genetic analysis were estimated to increase by 25% (odds ratio, 1.25 [95% CI, 1.16 to 1.35]) for participants with a measured 25-(OH)D concentration of 25 nmol/L compared with 50 nmol/L. Limitations: Analyses were restricted to a White European population. A genetic approach is best suited to providing proof of principle on causality, whereas the strength of the association is approximate. Conclusion: Our study supports a causal relationship between vitamin D deficiency and mortality. Additional research needs to identify strategies that meet the National Academy of Medicine's guideline of greater than 50 nmol/L and that reduce the premature risk for death associated with low vitamin D levels. Primary Funding Source: National Health and Medical Research Council.