Background There is marked interindividual variability in metabolism and resulting toxicity and effectiveness of drugs used for tuberculosis treatment. For isoniazid, mutations in the N-acetyltransferase 2 (NAT2) gene explain >88% of pharmacokinetic variability. However, weight-based dosing remains the norm globally. The potential clinical impact and cost-effectiveness of pharmacogenomic-guided therapy (PGT) are unknown. Methods We constructed a decision tree model to project lifetime costs and benefits of isoniazid PGT for drug-susceptible tuberculosis in Brazil, South Africa, and India. PGT was modeled to reduce isoniazid toxicity among slow NAT2 acetylators and reduce treatment failure among rapid acetylators. The genotyping test was assumed to cost the same as the GeneXpert test. The main outcomes were costs (2018 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Results In Brazil, PGT gained 19 discounted life-years (23 QALYs) and cost $11 064 per 1000 patients, a value of $476 per QALY gained. In South Africa, PGT gained 15 life-years (19 QALYs) and cost $33 182 per 1000 patients, a value of $1780 per QALY gained. In India, PGT gained 20 life-years (24 QALYs) and cost $13 195 per 1000 patients, a value of $546 per QALY gained. One-way sensitivity analyses showed the cost-effectiveness to be robust to all input parameters. Probabilistic sensitivity analyses were below per capita gross domestic product in all 3 countries in 99% of simulations. Conclusions Isoniazid PGT improves health outcomes and would be cost-effective in the treatment of drug-susceptible tuberculosis in Brazil, South Africa, and India.
Background Smartphone and wearable-based activity data provide an opportunity to remotely monitor functional capacity in patients. In this study, we assessed the ability of a home-based 6-minute walk test (6MWT) as well as passively collected activity data to supplement or even replace the in-clinic 6MWTs in patients with cardiovascular disease. Methods We enrolled 110 participants who were scheduled for vascular or cardiac procedures. Each participant was supplied with an iPhone and an Apple Watch running the VascTrac research app and was followed for 6 months. Supervised 6MWTs were performed during clinic visits at scheduled intervals. Weekly at-home 6MWTs were performed via the VascTrac app. The app passively collected activity data such as daily step counts. Logistic regression with forward feature selection was used to assess at-home 6MWT and passive data as predictors for “frailty” as measured by the gold-standard supervised 6MWT. Frailty was defined as walking <300m on an in-clinic 6MWT. Results Under a supervised in-clinic setting, the smartphone and Apple Watch with the VascTrac app were able to accurately assess ‘frailty’ with sensitivity of 90% and specificity of 85%. Outside the clinic in an unsupervised setting, the home-based 6MWT is 83% sensitive and 60% specific in assessing “frailty.” Passive data collected at home were nearly as accurate at predicting frailty on a clinic-based 6MWT as was a home-based 6MWT, with area under curve (AUC) of 0.643 and 0.704, respectively. Conclusions In this longitudinal observational study, passive activity data acquired by an iPhone and Apple Watch were an accurate predictor of in-clinic 6MWT performance. This finding suggests that frailty and functional capacity could be monitored and evaluated remotely in patients with cardiovascular disease, enabling safer and higher resolution monitoring of patients.
Background The 6-Mniute-Walk-Test (6MWT) is a validated proxy for frailty and a predictor of clinical outcomes, yet is not widely used due to implementation challenges. This comparative effectiveness study assesses the reliability and repeatability of a home-based 6MWT compared to in-clinic 6MWTs in patients with cardiovascular disease. Methods One hundred and ten (110) patients scheduled for cardiac or vascular surgery were enrolled during a study period from June 2018 to December 2019 at the Palo Alto VA Hospital. Subjects were provided with an Apple iPhone 7 and Apple Watch Series 3 loaded with the VascTrac research study application and performed a supervised in-clinic 6MWT during enrollment, at two weeks, one, three, and six months post-operatively. Subjects also received notifications to perform at-home smartphone-based 6MWTs once a week for a duration of six months. Test-retest reliability of in-clinic measurements and at-home measurements was assessed with an industry standard Cronbach’s alpha reliability test. Results Test-Retest Reliability for in-clinic ground truth 6MWT steps vs. in-clinic iPhone 6MWT steps was 0·99, showing high reliability between the two tested measurements. When comparing for in-clinic ground truth 6MWT steps vs. neighboring at-home iPhone 6MWT steps, reliability was 0·74. Conclusion Running the test-reliability test on both measurements shows that an iPhone 6MWT test is reliable compared to an in-clinic ground truth measurement in patients with cardiovascular disease.
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