Detection of SARS-CoV-2 in saliva by a low-cost LSPR-based sensor.

The SARS-CoV-2 pandemic started more than 3 years ago, but the containment of the spread is still a challenge. Screening is imperative for informed decision making by government authorities to contain the spread of the virus locally. The access to screening tests is disproportional, due to the lack of access to reagents, equipment, finances or because of supply chain disruptions. Low and middle-income countries have especially suffered with the lack of these resources. Here, we propose a low cost and easily constructed biosensor device based on localized surface plasmon resonance, or LSPR, for the screening of SARS-CoV-2. The biosensor device, dubbed "sensor" for simplicity, was constructed in two modalities: (1) viral detection in saliva and (2) antibody against COVID in saliva. Saliva collected from 18 patients were tested in triplicates. Both sensors successfully classified all COVID positive patients (among hospitalized and non-hospitalized). From the COVID negative patients 7/8 patients were correctly classified. For both sensors, sensitivity was determined as 100% (95% CI 79.5-100) and specificity as 87.5% (95% CI 80.5-100). The reagents and equipment used for the construction and deployment of this sensor are ubiquitous and low-cost. This sensor technology can then add to the potential solution for challenges related to screening tests in underserved communities.

Cost-effectiveness of remdesivir plus usual care versus usual care alone for hospitalized patients with COVID-19: an economic evaluation as part of the Canadian Treatments for COVID-19 (CATCO) randomized clinical trial.

BACKGROUND: The role of remdesivir in the treatment of hospitalized patients with COVID-19 remains ill-defined. We conducted a cost-effectiveness analysis alongside the Canadian Treatments for COVID-19 (CATCO) open-label, randomized clinical trial evaluating remdesivir. METHODS: Patients with COVID-19 in Canadian hospitals from Aug. 14, 2020, to Apr. 1, 2021, were randomly assigned to receive remdesivir plus usual care versus usual care alone. Taking a public health care payer's perspective, we collected in-hospital outcomes and health care resource utilization alongside estimated unit costs in 2020 Canadian dollars over a time horizon from randomization to hospital discharge or death. Data from 1281 adults admitted to 52 hospitals in 6 Canadian provinces were analyzed. RESULTS: The total mean cost per patient was $37 918 (standard deviation [SD] $42 413; 95% confidence interval [CI] $34 617 to $41 220) for patients randomly assigned to the remdesivir group and $38 026 (SD $46 021; 95% CI $34 480 to $41 573) for patients receiving usual care (incremental cost -$108 [95% CI -$4953 to $4737], p > 0.9). The difference in proportions of in-hospital deaths between remdesivir and usual care groups was -3.9% (18.7% v. 22.6%, 95% CI -8.3% to 1.0%, p = 0.09). The difference in proportions of incident invasive mechanical ventilation events between groups was -7.0% (8.0% v. 15.0%, 95% CI -10.6% to -3.4%, p = 0.006), whereas the difference in proportions of total mechanical ventilation events between groups was -5.7% (16.4% v. 22.1%, 95% CI -10.0% to -1.4%, p = 0.01). Remdesivir was the dominant intervention (but only marginally less costly, with mildly lower mortality) with an incalculable incremental cost effectiveness ratio; we report results of incremental costs and incremental effects separately. For willingness-to-pay thresholds of $0, $20 000, $50 000 and $100 000 per death averted, a strategy using remdesivir was cost-effective in 60%, 67%, 74% and 79% of simulations, respectively. The remdesivir costs were the fifth highest cost driver, offset by shorter lengths of stay and less mechanical ventilation. INTERPRETATION: From a health care payer perspective, treating patients hospitalized with COVID-19 with remdesivir and usual care appears to be preferrable to treating with usual care alone, albeit with marginal incremental cost and small clinical effects. The added cost of remdesivir was offset by shorter lengths of stay in the intensive care unit and less need for ventilation. STUDY REGISTRATION: ClinicalTrials. gov, no. NCT04330690.

A Systematic Review of Methods Used for Confounding Adjustment in Observational Economic Evaluations in Cardiology Conducted between 2013 and 2017.

Background. Observational economic evaluations (i.e., economic evaluations in which treatment allocation is not randomized) are prone to confounding bias. Prior reviews published in 2013 have shown that adjusting for confounding is poorly done, if done at all. Although these reviews raised awareness on the issues, it is unclear if their results improved the methodological quality of future work. We therefore aimed to investigate whether and how confounding was accounted for in recently published observational economic evaluations in the field of cardiology. Methods. We performed a systematic review of PubMed, Embase, Cochrane Library, Web of Science, and PsycInfo databases using a set of Medical Subject Headings and keywords covering topics in "observational economic evaluations in health within humans" and "cardiovascular diseases." Any study published in either English or French between January 1, 2013, and December 31, 2017, addressing our search criteria was eligible for inclusion in our review. Our protocol was registered with PROSPERO (CRD42018112391). Results. Forty-two (0.6%) out of 7523 unique citations met our inclusion criteria. Fewer than half of the selected studies adjusted for confounding (n = 19 [45.2%]). Of those that adjusted for confounding, propensity score matching (n = 8 [42.1%]) and other matching-based approaches were favored (n = 8 [42.1%]). Our results also highlighted that most authors who adjusted for confounding rarely justified their methodological choices. Conclusion. Our results indicate that adjustment for confounding is often ignored when conducting an observational economic evaluation. Continued knowledge translation efforts aimed at improving researchers' knowledge regarding confounding bias and methods aimed at addressing this issue are required and should be supported by journal editors.

A network perspective of engaging patients in specialist and chronic illness care: The 2014 International Health Policy Survey.

BACKGROUND: Patient engagement helps to improve health outcomes and health care quality. However, the overall relationships among patient engagement measures and health outcomes remain unclear. This study aims to integrate expert knowledge and survey data for the identification of measures that have extensive associations with other variables and can be prioritized to engage patients. METHODS: We used the 2014 International Health Policy Survey (IHPS), which provided information on elder adults in 11 countries with details in patient characteristics, healthcare experiences, and patient-physician communication. Patient engagement or support was measured with eight variables including patients' treatment choices, involvement, and treatment priority setting. Three types of care were identified: primary, specialist and chronic illness care. Specialists were doctors specializing in one area of health care. Chronic illness included eight chronic conditions surveyed. Expert knowledge was used to assist variable selection. We used Bayesian network models consisting of nodes that represented variables of interest and arcs that represented their relationships. RESULTS: Among 25,530 participants, the mean age was 68.51 years and 57.40% were females. The distributions of age, sex, education, and patient engagement were significantly different across countries. For chronic illness care, written plans provided by professionals were linked to treatment feasibility and helpfulness. Whether professionals contacted patients was associated with the availability of professionals they could reach for chronic illness care. For specialist care, if specialists provided treatment choices, patients were more likely to be involved and discuss about what mattered to them. CONCLUSION: The strategies to engage patients may depend on the types of care, specialist or chronic illness care. For the study on the observational IHPS data, network modeling is useful to integrate expert knowledge. We suggest considering other theory-based patient engagement in major surveys, as well as engaging patients in their healthcare by providing written plans and actively communicating with patients for chronic illnesses, and encouraging specialists to discuss and provide treatment options.

Methodological challenges in assessment of current use of warfarin among patients with atrial fibrillation using dispensation data from administrative health care databases.

PURPOSE: Algorithms to define current exposure to warfarin using administrative data may be imprecise. Study objectives were to characterize dispensation patterns, to measure gaps between expected and observed refill dates for warfarin and direct oral anticoagulants (DOACs). METHODS: Retrospective cohort study using administrative health care databases of the Régie de l'assurance-maladie du Québec. We identified every dispensation of warfarin, dabigatran, rivaroxaban, or apixaban for patients with AF initiating oral anticoagulants between 2010 and 2015. For each dispensation, we extracted date and duration. Refill gaps were calculated as difference between expected and observed dates of successive dispensation. Refill gaps were summarized using descriptive statistics. To account for repeated observations nested within patients and to assess the components of variance of refill gaps, we used unconditional multilevel linear models. RESULTS: We identified 61 516 new users. Majority were prescribed warfarin (60.3%), followed by rivaroxaban (16.4%), dabigatran (14.5%), apixaban (8.8%). Most frequent recorded duration of dispensation was 7 days, suggesting use of pharmacist-prepared weekly pillboxes. The average refill gap from multilevel model was higher for warfarin (9.28 days, 95%CI:8.97-9.59) compared with DOACs (apixaban 3.08 days, 95%CI: 2.96-3.20, dabigatran 3.70, 95%CI: 3.56-3.84, rivaroxaban 3.15, 95%CI: 3.03-3.27). The variance of refill gaps was greater among warfarin users than among DOAC users. CONCLUSIONS: Greater refill gaps for warfarin may reflect inadequate capture of the period covered by the number of dispensed pills recorded in administrative data. A time-dependent definition of exposure using dispensation data would lead to greater misclassification of warfarin than DOACs use.

Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study.

Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism.Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016.Setting Community based, using healthcare data from six jurisdictions in Canada and the United States.Participants 59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis.Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites.Results Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients.Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment.Trial registration Clinical trials NCT02833987.

A network perspective on patient experiences and health status: the Medical Expenditure Panel Survey 2004 to 2011.

BACKGROUND: There is a growing emphasis on the need to engage patients in order to improve the quality of health care and improve health outcomes. However, we are still lacking a comprehensive understanding on how different measures of patient experiences interact with one another or relate to health status. This study takes a network perspective to 1) study the associations between patient characteristics and patient experience in health care and 2) identify factors that could be prioritized to improve health status. METHODS: This study uses data from the two-year panels from the Medical Expenditure Panel Survey (MEPS) initiated between 2004 and 2011 in the United States. The 88 variables regarding patient health and experience with health care were identified through the MEPS documentation. Sex, age, race/ethnicity, and years of education were also included for analysis. The bnlearn package within R (v3.20) was used to 1) identify the structure of the network of variables, 2) assess the model fit of candidate algorithms, 3) cross-validate the network, and 4) fit conditional probabilities with the given structure. RESULTS: There were 51,023 MEPS interviewees aged 18 to 85 years (mean = 44, 95% CI = 43.9 to 44.2), with years of education ranging from 1 to 19 (mean = 7.4, 95% CI = 7.40 to 7.46). Among all, 55% and 74% were female and white, respectively. There were nine networks identified and 17 variables not linked to others, including death in the second years, sex, entry years to the MEPS, and relations of proxies. The health status in the second years was directly linked to that in the first years. The health care ratings were associated with how often professionals listened to them and whether professionals' explanation was understandable. CONCLUSIONS: It is feasible to construct Bayesian networks with information on patient characteristics and experiences in health care. Network models help to identify significant predictors of health care quality ratings. With temporal relationships established, the structure of the variables can be meaningful for health policy researchers, who search for one or a few key priorities to initiate interventions or health care quality improvement programs.

In vivo coronary artery plaque assessment with computed tomography angiography: is there an impact of iterative reconstruction on plaque volume and attenuation metrics?

Background Coronary computed tomography angiography (CTA) allows the evaluation of coronary plaque volume and low attenuation (lipid-rich) component, for plaque vulnerability assessment. Purpose To determine the effect of iterative reconstruction (IR) on coronary plaque volume and composition. Material and Methods Consecutive patients without coronary artery disease were prospectively enrolled for 256-slice CT. Images were reconstructed with both filtered back projection (FBP) and a hybrid IR algorithm (iDose4, Philips) levels 1, 3, 5, and 7. Coronary plaques were assessed according to predefined Hounsfield unit (HU) attenuation intervals, for total plaque and HU-interval volumes. Results Fifty-three patients (mean age, 53.6 years) were included. Noise was significantly decreased and signal-to-noise ratio (SNR) / contrast-to-noise (CNR) were both significantly improved at all IR levels in comparison to FBP. Plaque characterization was performed in 41 patients for a total of 125 plaques. Total plaque volume ranged from 104.4 ± 120.7 to 107.4 ± 128.9 mm3 and low attenuation plaque component from 40.5 ± 54.7 to 43.5 ± 58.9 mm3, with no statistically significant differences between all IR levels and FBP ( P = 0.786 and P ≥ 0.078, respectively). Conclusion IR improved image quality. Total and low attenuation plaque volumes were similar using either IR or FBP.

Cost effectiveness of 'on demand' HIV pre-exposure prophylaxis for non-injection drug-using men who have sex with men in Canada.

BACKGROUND: Recent trials report the efficacy of continuous tenofovir-based pre-exposure prophylaxis (PrEP) for prevention of HIV infection. The cost effectiveness of 'on demand' PrEP for non-injection drug-using men who have sex with men at high risk of HIV acquisition has not been evaluated. OBJECTIVE: To conduct an economic evaluation of the societal costs of HIV in Canada and evaluate the potential benefits of this PrEP strategy. METHODS: Direct HIV costs comprised outpatient, inpatient and emergency department costs, psychosocial costs and antiretroviral costs. Resource consumption estimates were derived from the Centre Hospitalier de l'Université de Montréal HIV cohort. Estimates of indirect costs included employment rate and work absenteeism. Costs for 'on demand' PrEP were modelled after an ongoing clinical trial. Cost-effectiveness analysis compared costs of 'on demand' PrEP to prevent one infection with lifetime costs of one HIV infection. Benefits were presented in terms of life-years and quality-adjusted life-years. RESULTS: The average annual direct cost of one HIV infection was $16,109 in the least expensive antiretroviral regimen scenario and $24,056 in the most expensive scenario. The total indirect cost was $11,550 per year. Total costs for the first year of HIV infection ranged from $27,410 to $35,358. Undiscounted lifetime costs ranged from $1,439,984 ($662,295 discounted at 3% and $448,901 at 5%) to $1,482,502 ($690,075 at 3% and $485,806 at 5%). The annual cost of PrEP was $12,001 per participant, and $621,390 per infection prevented. The PrEP strategy was cost-saving in all scenarios for undiscounted and 3% discounting rates. At 5% discounting rates, the strategy is largely cost-effective: according to least and most expensive scenarios, incremental cost-effectiveness ratios ranged from $60,311 to $47,407 per quality-adjusted life-year. CONCLUSION: This 'on demand' PrEP strategy ranges from cost-saving to largely cost-effective. The authors believe it represents an important public health strategy for the prevention of HIV transmission.

HISTORIQUE: De récents essais rendent compte de l'efficacité d'une prophylaxie préexposition continue à base de ténofovir (PrEP) pour prévenir l'infection par le VIH. La rentabilité de la PrEP sur demande n'a pas été évaluée chez les hommes qui ne consomment pas de drogues injectables, mais qui ont des relations sexuelles avec d'autres hommes très susceptibles de contracter le VIH. OBJECTIF: Réaliser une évaluation économique des coûts du VIH pour la société au Canada et évaluer les avantages potentiels de cette stratégie de PrEP. MÉTHODOLOGIE: Les coûts directs du VIH incluaient les coûts des rendez-vous ambulatoires, des séjours hospitaliers et des visites à l'urgence, les coûts psychosociaux et les coûts des antirétroviraux. L'évaluation de la consommation des ressources était dérivée de la cohorte de VIH du Centre hospitalier de l'Université de Montréal. Les évaluations des coûts indirects incluaient le taux d'emploi et l'absentéisme au travail. Les coûts de la PrEP sur demande reprenaient le modèle d'un essai clinique en cours. L'analyse de rentabilité reposait sur une comparaison des coûts de la PrEP sur demande pour prévenir une infection avec les coûts de traitement à vie d'une infection par le VIH. Les avantages étaient présentés d'après les années de vie et les années de vie pondérées par la qualité. RÉSULTATS: Le coût direct annuel moyen d'une infection par le VIH s'élevait à 16 109 $ d'après le scénario de posologie antirétrovirale le moins coûteux, et à 24 056 $ d'après le scénario le plus coûteux. Le coût indirect total s'élevait à 11 550 $ par année. Les coûts totaux pour la première année d'infection par le VIH oscillaient entre 27 410 $ et 35 358 $. Les coûts de traitement à vie non actualisés variaient entre 1 439 984 $ (662 295 $ actualisés à 3 % et 448 901 $, à 5 %) et 1 482 502 $ (690 075 $ à 3 % et 485 806 $ à 5 %). Le coût annuel de la PrEP était de 12 001 $ par participant, et de 621 390 $ par infection prévenue. La stratégie de PrEP était économique dans tous les scénarios non actualisés et actualisés à 3 %. Dans les scénarios actualisés à 5 %, la stratégie était largement rentable. En effet, selon les scénarios le moins et le plus coûteux, le rapport coût-efficacité différentiel se situait entre 60 311 $ et 47 407 $ par année de vie pondérée par la qualité. CONCLUSION: Cette stratégie de PrEP sur demande se situe quelque part entre la production d'économies et une rentabilité substantielle. Les auteurs sont d'avis qu'elle représente une importante stratégie de santé publique pour prévenir la transmission du VIH.

Impact of a restrictive drug access program on the risk of cardiovascular encounters in children exposed to ADHD medications.

BACKGROUND: ADHD medications increase clinical encounters for cardiovascular symptoms. Uncertain are the roles of differences in ADHD medications and restrictive practices by drug programs. METHODS: We conducted two nested case-control studies. The first was nested within a cohort of children de novo users of methylphenidate, amphetamines or atomoxetine and the second case-control study was nested within a subcohort of de novo amphetamine or atomoxetine users with no cardiovascular events prior to the first dispensing of either drug. The outcome for both studies was the composite of physician visits, emergency room visits or hospitalizations for cardiovascular reasons. Cases were matched on sex, age and date of entry within the cohorts, with up to 10 controls. Patients with an active dispensation of ADHD medications at the index date (and up to 90 days previously) were considered exposed. Conditional logistic regression was used to calculate odd ratios (OR). RESULTS: The full cohort comprised 38,495 patients. Among these patients, 3595 (9.3%) had no prior cardiovascular events (the subcohort). In the full cohort, an association was demonstrated with exposure to amphetamine and atomoxetine (but not methylphenidate) and the cardiovascular encounter outcomes. When the sub-cohort was analyzed the associations with amphetamine or atomoxetine were no longer evident. CONCLUSION: Reimbursement policies need to be considered when conducting observational studies. Had the analysis been conducted without consideration of these policies the results would have incorrectly identified amphetamine and atomoxetine as important risk factors for cardiovascular encounters.

Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: a cohort and nested case-control study using Québec's public health insurance database.

BACKGROUND: Morbidity associated with cardiovascular disease is increasing in the HIV-infected population. We aimed to study the impact of HIV and of antiretrovirals on acute myocardial infarction (AMI). METHODS: We performed a cohort and a nested case-control study using the dataset of the Régie de l'Assurance Maladie du Québec. HIV-positive patients were identified using ICD-9 diagnostic codes and matched to HIV-negative patients. Within the HIV-positive cohort, cases of AMI were identified and matched to HIV-positive patients without AMI. The coprimary outcomes were the risk of AMI associated with HIV exposure in the cohort study and that associated with exposure to antiretrovirals in the case-control study. Data were analysed using Poisson and conditional logistic regression. RESULTS: About 7053 HIV-positive patients were matched to 27,681 HIV-negative patients. Incidence rates of AMI in the HIV+ cohort was 3.88 95% confidence interval (CI) (3.26 to 4.58) per 1000 patient-years, compared to 2.21 95% CI (1.93 to 2.52) per 1000 patient-years in the HIV cohort. The adjusted incidence ratio of AMI for HIV-infected patients was 2.11 95%CI (1.69 to 2.63). Among HIV+ patients, 125 AMI cases were matched with 1084 HIV+ patients. We found increased odds ratio (95% CI) of AMI associated with any exposure to abacavir 1.79 (1.16 to 2.76), P = 0.02, efavirenz 1.83 (1.21 to 2.76) P = 0.004, lopinavir 1.98 (1.24 to 3.16) P = 0.004, and ritonavir 2.29 (1.48 to 3.54) P < 0.001. CONCLUSIONS: HIV+ individuals were at higher risk of AMI than the general population, and several antiretrovirals were associated with an increased risk of AMI. Results should be interpreted with caution in absence of data on smoking and HIV clinical status.