Ethical Framework for Assessing Manual and Digital Contact Tracing for COVID-19

The coronavirus disease 2019 (COVID-19) pandemic has challenged the traditional public health balance between benefiting the good of the community through contact tracing and restricting individual liberty. This article first analyzes important technical and ethical issues regarding new smartphone apps that facilitate contact tracing and exposure notification. It then presents a framework for assessing contact tracing, whether manual or digital: the effectiveness at mitigating the pandemic; acceptability of risks, particularly privacy; and equitable distribution of benefits and risks. Both manual and digital contact tracing require public trust, engagement of minority communities, prompt COVID-19 testing and return of results, and high adherence with physical distancing and use of masks.

Cases in Precision Medicine: Genetic Testing to Predict Future Risk for Disease in a Healthy Patient

Genetic testing is performed more routinely in clinical practice, and direct-to-consumer tests are widely available. It has obvious appeal as a preventive health measure. Clinicians and their healthy patients increasingly inquire about genetic testing as a tool for predicting diseases, such as cancer, heart disease, or dementia. Despite demonstrated utility for diagnosis in the setting of many diseases, genetic testing still has many limitations as a predictive tool for healthy persons. This article uses a hypothetical case to review key considerations for predictive genetic testing.

Preventing Hospital Readmission for Patients With Comorbid Substance Use Disorder: A Randomized Trial: Annals of Internal Medicine: Vol 174, No 7

Background: Hospitalized patients with comorbid substance use disorders (SUDs) are at high risk for poor outcomes, including readmission and emergency department (ED) use. Objective: To determine whether patient navigation services reduce hospital readmissions. Design: Randomized controlled trial comparing Navigation Services to Avoid Rehospitalization (NavSTAR) versus treatment as usual (TAU). (ClinicalTrials.gov: NCT02599818) Setting: Urban academic hospital in Baltimore, Maryland, with an SUD consultation service. Participants: 400 hospitalized adults with comorbid SUD (opioid, cocaine, or alcohol). Intervention: NavSTAR used proactive case management, advocacy, service linkage, and motivational support to resolve internal and external barriers to care and address SUD, medical, and basic needs for 3 months after discharge. Measurements: Data on inpatient readmissions (primary outcome) and ED visits for 12 months were obtained for all participants via the regional health information exchange. Entry into SUD treatment, substance use, and related outcomes were assessed at 3-, 6-, and 12-month follow-up. Results: Participants had high levels of acute care use: 69% had an inpatient readmission and 79% visited the ED over the 12-month observation period. Event rates per 1000 person-days were 6.05 (NavSTAR) versus 8.13 (TAU) for inpatient admissions (hazard ratio, 0.74 [95% CI, 0.58 to 0.96]; P = 0.020) and 17.66 (NavSTAR) versus 27.85 (TAU) for ED visits (hazard ratio, 0.66 [CI, 0.49 to 0.89]; P = 0.006). Participants in the NavSTAR group were less likely to have an inpatient readmission within 30 days than those receiving TAU (15.5% vs. 30.0%; P < 0.001) and were more likely to enter community SUD treatment after discharge (P = 0.014; treatment entry within 3 months, 50.3% NavSTAR vs. 35.3% TAU). Limitation: Single-site trial, which limits generalizability. Conclusion: Patient navigation reduced inpatient readmissions and ED visits in this clinically challenging sample of hospitalized patients with comorbid SUDs. Primary Funding Source: National Institute on Drug Abuse.

Midodrine for the Prevention of Vasovagal Syncope: A Randomized Clinical Trial: Annals of Internal Medicine: Vol 174, No 10

Background: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope. Objective: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions. Design: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481) Setting: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom. Patients: Patients with recurrent vasovagal syncope and no serious comorbid conditions. Intervention: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months. Measurements: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up. Results: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups. Limitation: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center. Conclusion: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden. Primary Funding Source: The Canadian Institutes of Health Research.

COVID-19 Mortality Risk in Down Syndrome: Results From a Cohort Study of 8 Million Adults

Race and the False Precision of Glomerular Filtration Rate Estimates

The Value of Total Knee Replacement in Patients With Knee Osteoarthritis and a Body Mass Index of 40 kg/m2 or Greater: A Cost-Effectiveness Analysis: Annals of Internal Medicine: Vol 174, No 6

Background: Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population. Objective: To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis. Design: Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater. Data Sources: Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data. Target Population: Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States. Time Horizon: Lifetime. Perspective: Health care sector. Intervention: Total knee replacement. Outcome Measures: Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. Results of Base-Case Analysis: Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100. Results of Sensitivity Analysis: In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively. Limitation: Data are derived from several sources. Conclusion: From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

Racism and Health in the United States: A Policy Statement From the American College of Physicians

Racial minorities in the United States have reported experiencing widespread racism throughout all aspects of life, from housing to education to employment. Existing research has examined the role of racism, discrimination, and violence in one's interaction with the health care system and their association with poorer mental and physical health. Systemic racism that underlies the fabric of society often manifests itself in prominent institutions, such as law enforcement agencies, regardless of individual intent. Overt and covert racist laws and policies, personal implicit biases, and other factors result in Black individuals and other people of color being the subject of law enforcement violence and criminal justice system interactions at disproportionately high rates. The demonstrated association between discriminatory law enforcement practices and violence and personal and community health necessitates treating these issues as public health issues worthy of a public policy intervention. Addressing some of the sources of institutional racism and harm through transparency and accountability measures is the first of many steps required to begin correcting historical racial injustices.

Spatial Inequities in COVID-19 Testing, Positivity, Confirmed Cases, and Mortality in 3 U.S. Cities: An Ecological Study: Annals of Internal Medicine: Vol 174, No 7

Background: Preliminary evidence has shown inequities in coronavirus disease 2019 (COVID-19)–related cases and deaths in the United States. Objective: To explore the emergence of spatial inequities in COVID-19 testing, positivity, confirmed cases, and mortality in New York, Philadelphia, and Chicago during the first 6 months of the pandemic. Design: Ecological, observational study at the ZIP code tabulation area (ZCTA) level from March to September 2020. Setting: Chicago, New York, and Philadelphia. Participants: All populated ZCTAs in the 3 cities. Measurements: Outcomes were ZCTA-level COVID-19 testing, positivity, confirmed cases, and mortality cumulatively through the end of September 2020. Predictors were the Centers for Disease Control and Prevention Social Vulnerability Index and its 4 domains, obtained from the 2014–2018 American Community Survey. The spatial autocorrelation of COVID-19 outcomes was examined by using global and local Moran I statistics, and estimated associations were examined by using spatial conditional autoregressive negative binomial models. Results: Spatial clusters of high and low positivity, confirmed cases, and mortality were found, co-located with clusters of low and high social vulnerability in the 3 cities. Evidence was also found for spatial inequities in testing, positivity, confirmed cases, and mortality. Specifically, neighborhoods with higher social vulnerability had lower testing rates and higher positivity ratios, confirmed case rates, and mortality rates. Limitations: The ZCTAs are imperfect and heterogeneous geographic units of analysis. Surveillance data were used, which may be incomplete. Conclusion: Spatial inequities exist in COVID-19 testing, positivity, confirmed cases, and mortality in 3 large U.S. cities. Primary Funding Source: National Institutes of Health.

The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults: A Response-Adaptive, Randomized Clinical Trial: Annals of Internal Medicine: Vol 174, No 2

Background: Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences. Objective: To compare the effects of 4 doses of vitamin D3 supplements on falls. Design: 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333) Setting: 2 community-based research units. Participants: 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L. Intervention: 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose. Measurements: Time to first fall or death over 2 years (primary outcome). Results: During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n = 308) and those randomly assigned to receive 200 IU/d (n = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]). Limitations: The control group received 200 IU of vitamin D3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached. Conclusion: In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/d or higher. Primary Funding Source: National Institute on Aging.