Alcohol Consumption-Related Metabolites in Relation to Colorectal Cancer and Adenoma: Two Case-Control Studies Using Serum Biomarkers

Alcohol is a known carcinogen that may be associated with colorectal cancer. However, most epidemiologic studies assess alcoholic beverage consumption using self-reported data, leading to potential exposure misclassification. Biomarkers of alcohol consumption may provide an alternative, complementary approach that reduces misclassification and incorporates individual differences in alcohol metabolism. Therefore, we evaluated the relationship between previously identified alcohol consumption-related metabolites and colorectal cancer and adenoma using serum metabolomics data from two studies. Data on colorectal cancer were obtained from a nested case-control study of 502 US adults (252 cases, 250 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Data on colorectal adenoma were obtained from a case-control study of 197 US adults (120 cases, 77 controls) from the Navy Colon Adenoma Study. Unconditional multivariable logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) for eight alcohol consumption-related metabolites identified in a previous analysis: ethyl glucuronide; 4-androstene-3beta,17beta-diol disulfate 1; 5-alpha-androstan-3beta,17beta-diol disulfate; 16-hydroxypalmitate; bilirubin (E,Z or Z,E); cyclo (-leu-pro); dihomo-linoleate (20:2n6); and palmitoleate (16:1n7). We found no clear association between these alcohol consumption-related metabolites and either endpoint. However, we did observe an inverse association between cyclo (-leu-pro) and colorectal adenoma that was only observed in the highest metabolite quantile (OR 4th vs. 1st Quantile = 0.30, 95% CI: 0.12–0.78; P-trend = 0.047), but no association for colorectal cancer. In conclusion, there were no adverse associations between alcohol consumption-related metabolites and colorectal cancer or adenoma

Clinical outcomes and cost-effectiveness of COVID-19 vaccination in South Africa

Low- and middle-income countries are implementing COVID-19 vaccination strategies in light of varying vaccine efficacies and costs, supply shortages, and resource constraints. Here, we use a microsimulation model to evaluate clinical outcomes and cost-effectiveness of a COVID-19 vaccination program in South Africa. We varied vaccination coverage, pace, acceptance, effectiveness, and cost as well as epidemic dynamics. Providing vaccines to at least 40% of the population and prioritizing vaccine rollout prevented >9 million infections and >73,000 deaths and reduced costs due to fewer hospitalizations. Model results were most sensitive to assumptions about epidemic growth and prevalence of prior immunity to SARS-CoV-2, though the vaccination program still provided high value and decreased both deaths and health care costs across a wide range of assumptions. Vaccination program implementation factors, including prompt procurement, distribution, and rollout, are likely more influential than characteristics of the vaccine itself in maximizing public health benefits and economic efficiency

Cost-effectiveness of a novel lipoarabinomannan test for tuberculosis in patients with HIV

BACKGROUND: A novel urine lipoarabinomannan assay (FujiLAM) has higher sensitivity and higher cost than the first-generation AlereLAM assay. We evaluated the cost-effectiveness of FujiLAM for tuberculosis testing among hospitalized people with HIV irrespective of symptoms. METHODS: We used a microsimulation model to project clinical and economic outcomes of three testing strategies: 1) sputum Xpert MTB/RIF (Xpert); 2) sputum Xpert plus urine AlereLAM (Xpert+AlereLAM); 3) sputum Xpert plus urine FujiLAM (Xpert+FujiLAM). The modelled cohort matched that of a two-country clinical trial. We applied diagnostic yields from a retrospective study (yields for Xpert/Xpert+AlereLAM/Xpert+FujiLAM among those with CD4<200/µL: 33%/62%/70%; among those with CD4≥200/µL: 33%/35%/47%). Costs of Xpert/AlereLAM/FujiLAM were USD15/3/6 (South Africa) and USD25/3/6 (Malawi). Xpert+FujiLAM was considered cost-effective if its incremental cost-effectiveness ratio (USD/year-of-life saved) was <$940 (South Africa) and <$750 (Malawi). We varied key parameters in sensitivity analysis and performed a budget impact analysis of implementing FujiLAM countrywide. RESULTS: Compared with Xpert+AlereLAM, Xpert+FujiLAM increased life expectancy by 0.2 years for those tested in South Africa and Malawi. Xpert+FujiLAM was cost-effective in both countries. Xpert+FujiLAM for all patients remained cost-effective compared with sequential testing and CD4-stratified testing strategies. FujiLAM use added 3.5% (South Africa) and 4.7% (Malawi) to five-year healthcare costs of tested patients, primarily reflecting ongoing HIV treatment costs among survivors. CONCLUSIONS: FujiLAM with Xpert for tuberculosis testing in hospitalized people with HIV is likely to increase life expectancy and be cost-effective at the currently anticipated price in South Africa and Malawi. Additional studies should evaluate FujiLAM in clinical practice settings

Clinical Outcomes, Costs, and Cost-effectiveness of Strategies for Adults Experiencing Sheltered Homelessness During the COVID-19 Pandemic

Importance: Approximately 356 000 people stay in homeless shelters nightly in the United States. They have high risk of contracting coronavirus disease 2019 (COVID-19). / Objective: To assess the estimated clinical outcomes, costs, and cost-effectiveness associated with strategies for COVID-19 management among adults experiencing sheltered homelessness. / Design, Setting, and Participants: This decision analytic model used a simulated cohort of 2258 adults residing in homeless shelters in Boston, Massachusetts. Cohort characteristics and costs were adapted from Boston Health Care for the Homeless Program. Disease progression, transmission, and outcomes data were taken from published literature and national databases. Surging, growing, and slowing epidemics (effective reproduction numbers [Re], 2.6, 1.3, and 0.9, respectively) were examined. Costs were from a health care sector perspective, and the time horizon was 4 months, from April to August 2020. / Exposures: Daily symptom screening with polymerase chain reaction (PCR) testing of individuals with positive symptom screening results, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternative care sites (ACSs) for mild or moderate COVID-19, and temporary housing were each compared with no intervention. / Main Outcomes and Measures: Cumulative infections and hospital-days, costs to the health care sector (US dollars), and cost-effectiveness, as incremental cost per case of COVID-19 prevented. / Results: The simulated population of 2258 sheltered homeless adults had a mean (SD) age of 42.6 (9.04) years. Compared with no intervention, daily symptom screening with ACSs for pending tests or confirmed COVID-19 and mild or moderate disease was associated with 37% fewer infections (1954 vs 1239) and 46% lower costs ($6.10 million vs$3.27 million) at an Re of 2.6, 75% fewer infections (538 vs 137) and 72% lower costs ($1.46 million vs$0.41 million) at an Re of 1.3, and 51% fewer infections (174 vs 85) and 51% lower costs ($0.54 million vs$0.26 million) at an Re of 0.9. Adding PCR testing every 2 weeks was associated with a further decrease in infections; incremental cost per case prevented was $1000 at an Re of 2.6,$27 000 at an Re of 1.3, and $71 000 at an Re of 0.9. Temporary housing with PCR every 2 weeks was most effective but substantially more expensive than other options. Compared with no intervention, temporary housing with PCR every 2 weeks was associated with 81$39.12 million) at an Re of 2.6, 82% fewer infections (95) and 2568% higher costs ($38.97 million) at an Re of 1.3, and 59$38.94 million) at an Re of 0.9. Results were sensitive to cost and sensitivity of PCR and ACS efficacy in preventing transmission. / Conclusions and Relevance: In this modeling study of simulated adults living in homeless shelters, daily symptom screening and ACSs were associated with fewer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decreased costs compared with no intervention. In a modeled surging epidemic, adding universal PCR testing every 2 weeks was associated with further decrease in SARS-CoV-2 infections at modest incremental cost and should be considered during future surges

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa

Background Healthcare resource constraints in low and middle-income countries necessitate selection of cost-effective public health interventions to address COVID-19. Methods We developed a dynamic COVID-19 microsimulation model to evaluate clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal, South Africa. Interventions assessed were Healthcare Testing (HT), where diagnostic testing is performed only for those presenting to healthcare centres; Contact Tracing (CT) in households of cases; Isolation Centres (IC), for cases not requiring hospitalisation; community health worker-led Mass Symptom Screening and diagnostic testing for symptomatic individuals (MS); and Quarantine Centres (QC), for contacts who test negative. Given uncertainties about epidemic dynamics in South Africa, we evaluated two main epidemic scenarios over 360 days, with effective reproduction numbers (R e ) of 1.5 and 1.2. We compared HT, HT+CT, HT+CT+IC, HT+CT+IC+MS, HT+CT+IC+QC, and HT+CT+IC+MS+QC, considering strategies with incremental cost-effectiveness ratio (ICER) <US$1,290/year-of-life saved (YLS) to be cost-effective. Findings With R e 1.5, HT resulted in the most COVID-19 deaths and lowest costs over 360 days. Compared with HT, HT+CT+IC+MS reduced mortality by 76$350/YLS). HT+CT+IC+MS+QC provided the greatest reduction in mortality, but increased costs by 95% compared with HT+CT+IC+MS and was not cost-effective (ICER $8,000/YLS). With R e 1.2, HT+CT+IC+MS was the least costly strategy, and HT+CT+IC+MS+QC was not cost-effective (ICER$294,320/YLS). Interpretation In South Africa, a strategy of household contact tracing, isolation, and mass symptom screening would substantially reduce COVID-19 mortality and be cost-effective. Adding quarantine centres for COVID-19 contacts is not cost-effective

Cost-effectiveness of public health strategies for COVID-19 epidemic control in South Africa: a microsimulation modelling study

Background: Health-care resource constraints in low-income and middle-income countries necessitate the identification of cost-effective public health interventions to address COVID-19. We aimed to develop a dynamic COVID-19 microsimulation model to assess clinical and economic outcomes and cost-effectiveness of epidemic control strategies in KwaZulu-Natal province, South Africa. Methods: We compared different combinations of five public health interventions: health-care testing alone, where diagnostic testing is done only for individuals presenting to health-care centres; contact tracing in households of cases; isolation centres, for cases not requiring hospital admission; mass symptom screening and molecular testing for symptomatic individuals by community health-care workers; and quarantine centres, for household contacts who test negative. We calibrated infection transmission rates to match effective reproduction number (Re) estimates reported in South Africa. We assessed two main epidemic scenarios for a period of 360 days, with an Re of 1·5 and 1·2. Strategies with incremental cost-effectiveness ratio (ICER) of less than US$3250 per year of life saved were considered cost-effective. We also did sensitivity analyses by varying key parameters (Re values, molecular testing sensitivity, and efficacies and costs of interventions) to determine the effect on clinical and cost projections. Findings: When Re was 1·5, health-care testing alone resulted in the highest number of COVID-19 deaths during the 360-day period. Compared with health-care testing alone, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres reduced mortality by 94$340 per year of life saved). In settings where quarantine centres were not feasible, a combination of health-care testing, contact tracing, use of isolation centres, and mass symptom screening was cost-effective compared with health-care testing alone (ICER $590 per year of life saved). When Re was 1·2, health-care testing, contact tracing, use of isolation centres, and use of quarantine centres was the least costly strategy, and no other strategies were cost-effective. In sensitivity analyses, a combination of health-care testing, contact tracing, use of isolation centres, mass symptom screening, and use of quarantine centres was generally cost-effective, with the exception of scenarios in which Re was 2·6 and when efficacies of isolation centres and quarantine centres for transmission reduction were reduced. Interpretation: In South Africa, strategies involving household contact tracing, isolation, mass symptom screening, and quarantining household contacts who test negative would substantially reduce COVID-19 mortality and would be cost-effective. The optimal combination of interventions depends on epidemic growth characteristics and practical implementation considerations