Factors associated with COVID-19 viral and antibody test positivity and assessment of test concordance: a retrospective cohort study using electronic health records from the USA.

OBJECTIVES: To identify factors associated with COVID-19 test positivity and assess viral and antibody test concordance. DESIGN: Observational retrospective cohort study. SETTING: Optum de-identified electronic health records including over 700 hospitals and 7000 clinics in the USA. PARTICIPANTS: There were 891 754 patients who had a COVID-19 test identified in their electronic health record between 20 February 2020 and 10 July 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Per cent of viral and antibody tests positive for COVID-19 ('positivity rate'); adjusted ORs for factors associated with COVID-19 viral and antibody test positivity; and per cent concordance between positive viral and subsequent antibody test results. RESULTS: Overall positivity rate was 9% (70 472 of 771 278) and 12% (11 094 of 91 741) for viral and antibody tests, respectively. Positivity rate was inversely associated with the number of individuals tested and decreased over time across regions and race/ethnicities. Antibody test concordance among patients with an initial positive viral test was 91% (71%-95% depending on time between tests). Among tests separated by at least 2 weeks, discordant results occurred in 7% of patients and 9% of immunocompromised patients. Factors associated with increased odds of viral and antibody positivity in multivariable models included: male sex, Hispanic or non-Hispanic black or Asian race/ethnicity, uninsured or Medicaid insurance and Northeast residence. We identified a negative dose effect between the number of comorbidities and viral and antibody test positivity. Paediatric patients had reduced odds (OR=0.60, 95% CI 0.57 to 0.64) of a positive viral test but increased odds (OR=1.90, 95% CI 1.62 to 2.23) of a positive antibody test compared with those aged 18-34 years old. CONCLUSIONS: This study identified sociodemographic and clinical factors associated with COVID-19 test positivity and provided real-world evidence demonstrating high antibody test concordance among viral-positive patients.

Antiviral use is associated with a decrease in the rate of influenza-related complications, health care resource utilization, and costs.

AIMS: To determine the effect of antiviral agents on influenza-related complications, health care resource utilization (HRU), and costs over three influenza seasons (2014-2016). METHODS: This retrospective cohort study used claims data from the U.S. MarketScan Research Databases. Patients with a diagnosis code for influenza during the 2014-2016 seasons in an outpatient setting, with continuous enrollment from 1 year before to 91 d after diagnosis, were included. Patients who received an antiviral within 48 h of diagnosis were identified and propensity score-matched to a comparator cohort of untreated patients on baseline demographics, comorbid conditions, and HRU. Outcomes were assessed at days 30 and 90 after diagnosis and included respiratory-related complications (all respiratory-related and selected respiratory-related conditions [influenza, asthma, chronic obstructive pulmonary disease, or infection]), HRU, and costs. RESULTS: Treated and matched untreated cohorts each consisted of 362,818 patients. HRU was significantly lower in the treated cohort compared with the untreated cohort at 30 and 90 d after diagnosis, respectively (hospitalizations: 0.6% vs. 0.8% and 1.2% vs. 1.6%; emergency department [ED] visits: 4.1% vs. 4.9% and 7.9% vs. 9.2%; intensive care unit/critical care unit (ICU/CCU) admissions: 0.2% vs. 0.4% and 0.4% vs. 0.6%). Respiratory-related HRU was lower in the treated cohort at both 30 and 90 d after diagnosis (p < .0001 for both periods). Mean all-cause total costs (including prescription costs) were significantly reduced in the treated group (day 30: $633 vs. $778; day 90: $1778 vs. $2119), despite higher prescription costs in the treated group. LIMITATIONS: The study was retrospective and subject to residual selection bias, despite propensity score matching. Additionally, despite its potential relevance to influenza severity, vaccination status was not available in our data. CONCLUSIONS: Antiviral influenza treatment is associated with a significant reduction in complications, HRU, and costs at 30 and 90 d after diagnosis.

Regional variations in adverse event reporting rates and ACR responses in placebo/standard-of-care arms of rheumatoid arthritis trials.

OBJECTIVE: Clinical trials are increasingly globalized, and adverse event (AE) rates and treatment responses may differ by geographical region. This study assessed regional differences in AE reporting rates and ACR response rates (ACR20/50) in patients with RA who received placebo/standard-of-care treatment in clinical trials. METHODS: Patients from the placebo arms of 7 RA trials in the TransCelerate Biopharma Inc database were grouped into 5 geographical regions (Asia, Latin America, Russian Federation and Eastern Europe [RFEE], USA, and Western Europe). Differences in demographics, AE reporting rates and ACR response were evaluated using descriptive statistics and omnibus tests for significance; pairwise comparisons were made between regions, with false discovery rate correction for multiple comparisons. RESULTS: Among 970 patients included, week 12 AE rates were significantly lower in the RFEE than in Asia, Latin America and the USA (22% vs 51%, 49% and 53%, respectively; P < 0.05 after false discovery rate correction). Similar differences in AE rates across geographical regions were seen at week 52. Among 747 patients with ACR data, the lowest response rates were observed in the USA (ACR20, 22%) and RFEE (ACR50, 3%); the highest response rates were seen in Western Europe (ACR20, 43%) and Latin America (ACR50, 15%). Only the differences in ACR50 response between the RFEE and Latin America remained significant after false discovery rate correction. CONCLUSION: These placebo/standard-of-care arm data revealed significant regional differences in AE reporting rates and ACR50 response rates. Regional distribution of patients should be considered when conducting RA clinical trials, particularly during recruitment.

Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical models.

BACKGROUND: WHO's 2013 revisions to its Consolidated Guidelines on antiretroviral drugs recommend routine viral load monitoring, rather than clinical or immunological monitoring, as the preferred monitoring approach on the basis of clinical evidence. However, HIV programmes in resource-limited settings require guidance on the most cost-effective use of resources in view of other competing priorities such as expansion of antiretroviral therapy coverage. We assessed the cost-effectiveness of alternative patient monitoring strategies. METHODS: We evaluated a range of monitoring strategies, including clinical, CD4 cell count, and viral load monitoring, alone and together, at different frequencies and with different criteria for switching to second-line therapies. We used three independently constructed and validated models simultaneously. We estimated costs on the basis of resource use projected in the models and associated unit costs; we quantified impact as disability-adjusted life years (DALYs) averted. We compared alternatives using incremental cost-effectiveness analysis. FINDINGS: All models show that clinical monitoring delivers significant benefit compared with a hypothetical baseline scenario with no monitoring or switching. Regular CD4 cell count monitoring confers a benefit over clinical monitoring alone, at an incremental cost that makes it affordable in more settings than viral load monitoring, which is currently more expensive. Viral load monitoring without CD4 cell count every 6-12 months provides the greatest reductions in morbidity and mortality, but incurs a high cost per DALY averted, resulting in lost opportunities to generate health gains if implemented instead of increasing antiretroviral therapy coverage or expanding antiretroviral therapy eligibility. INTERPRETATION: The priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per µL, and then at a CD4 cell count lower than 500 cells per µL, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future. FUNDING: Bill & Melinda Gates Foundation, WHO.

How do different eligibility guidelines for antiretroviral therapy affect the cost-effectiveness of routine viral load testing in sub-Saharan Africa?

BACKGROUND: Increased eligibility guidelines of antiretroviral therapy (ART) may lead to greater routine viral load monitoring. However, in resource-constrained settings, the additional resources required by greater routine viral load monitoring may impair ability to comply with expanded eligibility guidelines for ART. OBJECTIVE: We use a published validated computer simulation of the HIV epidemic in East African countries (expanded to include transmission as well as disease progression) to evaluate the cost-effectiveness of routine viral load monitoring. METHODS: We explored alternative scenarios regarding cost, frequency, and switching threshold of routine viral load monitoring (including every 6 or every 12 months; and switching thresholds of 1000, or 10 000 copies/ml), as well as alternative scenarios regarding ART initiation (200, 350, 500  cells/µl, and no CD4 cell threshold). For each ART initiation strategy, we sought to identify the viral load monitoring strategy at which the incremental cost-effectiveness ratio (ICER) of more frequent routine viral load testing became more favorable than the ICER of more expansive ART eligibility. Cost inputs were based on data provided by the Academic Model Providing Access to Healthcare (AMPATH), and disease progression inputs were based on prior published work. We used a discount rate of 3%, a time horizon of 20 years, and a payer perspective. RESULTS: Across a wide range of scenarios, and even when considering the beneficial effect of virological monitoring at reducing HIV transmission, earlier ART initiation conferred far greater health benefits for resources spent than routine virological testing, with ICERs of approximately $1000 to $2000 for earlier ART initiation, versus ICERs of approximately $5000 to $25 000 for routine virological monitoring. ICERs of viral load testing were insensitive to the cost of the viral load test, because most of the costs originated from the downstream higher costs of later regimens. ICERs of viral load testing were very sensitive to the relative cost of second-line compared with first-line regimens, assuming favorable value when the costs of these regimens were equal. CONCLUSION: If all HIV patients are not yet treated with ART starting at 500  cells/µl and costs of second regimens remain substantially more expensive than first-line regimens, resources would buy more population health if they are spent on earlier ART rather than being spent on routine virological testing.

Biology as population dynamics: heuristics for transmission risk.

Population-type models, accounting for phenomena such as population lifetimes, mixing patterns, recruitment patterns, genetic evolution and environmental conditions, can be usefully applied to the biology of HIV infection and viral replication. A simple dynamic model can explore the effect of a vaccine-like stimulus on the mortality and infectiousness, which formally looks like fertility, of invading virions; the mortality of freshly infected cells; and the availability of target cells, all of which impact on the probability of infection. Variations on this model could capture the importance of the timing and duration of different key events in viral transmission, and hence be applied to questions of mucosal immunology. The dynamical insights and assumptions of such models are compatible with the continuum of between- and within-individual risks in sexual violence and may be helpful in making sense of the sparse data available on the association between HIV transmission and sexual violence.

Rural immersion as an instructional method in northern community health.

In 2004, a class of six students traveled with three faculty mentors to seven Alaska communities as part of a course designed to ground young researchers' aspirations in the pragmatics of collaborative, community-based research. This paper, authored by the students involved, discusses the process from start to finish. Beginning researchers in rural health are often daunted not by a lack of ability or ideas, but by basic issues of logistics, trust and respect. Unfortunately, they tend to remain unacquainted with these considerations until something goes wrong, and come to frame the research process as a succession of hindrances to be overcome rather than a fluid and collaborative endeavor. By placing students in working relationships with rural residents and Native elders at an early stage, the project aims to minimize common missteps and shorten the learning curve. It is hoped that our experiences can point the way toward similar efforts.