Quality of anticoagulant control and patient experience associated with long-term warfarin in Canadian patients with non-valvular atrial fibrillation: A multicentre, prospective study.

BACKGROUND: Despite the fact that direct oral anticoagulants (DOACs) are favoured over warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), physicians need to maintain competence in using and monitoring warfarin since many patients have contraindications or other barriers to using DOACs. Unlike DOACs, warfarin therapy requires regular blood testing to ensure that it is within a target range to ensure efficacy and safety. There is limited real-world data on the adequacy of warfarin control and the cost and burden of monitoring warfarin therapy in Canadian NVAF patients. OBJECTIVES: In a large cohort of Canadian patients with NVAF on warfarin we assessed time in therapeutic range (TTR), determinants of TTR, process of care, direct costs, health related quality of life and loss of work time and productivity related to warfarin therapy. METHODS: Five hundred and fifty one patients with NVAF, either newly initiated or stable on warfarin were prospectively enrolled across 9 Canadian provinces from primary care practices and anticoagulant clinics. Participating physicians provided baseline demographic and medical information. Patients completed diaries for 48 weeks, capturing information about International Normalized Ratio (INR) test results, test locations, process of INR monitoring, direct costs of travel, health-related quality of life and work productivity measures. TTR was estimated using linear interpolation of INR results and linear regression used to investigate associations between TTR and factors (defined a priori). RESULTS: Four hundred and eighty (87.1%) patients had complete follow-up with an overall TTR of 74.4% based on 7,175 physician-reported INR values from 501 patients. 88% of this cohort were monitored through routine medical care (RMC). The average number of INRs per patient during the 48-week period was 14.1 (standard deviation (SD) = 8.3) tests with a mean duration of 23.8 (SD = 11.1) days between tests. We did not find a relationship between TTR and age, sex, presence of major comorbidities, patient's province of residence or rural vs. urban residence. 12% of patients monitored through anticoagulant clinics had significantly better TTR than patients monitored through RMC (82% vs. 74%; 95% confidence interval: -13.8, -1.2; p = 0.02). Health related quality of life utility values were high and remained consistent throughout the study. The majority of patients reported no impact on either work productivity or impairment of regular activities due to being on long-term warfarin treatment. CONCLUSIONS: We showed excellent overall TTR in an observed Canadian cohort, with monitoring through a dedicated anticoagulant clinic being associated with a statistically and clinically significant improvement in TTR. The burden of warfarin therapy on patients' health related quality of life or daily work and activities was low.

The economic burden of patient safety targets in acute care: a systematic review.

BACKGROUND: Our objective was to determine the quality of literature in costing of the economic burden of patient safety. METHODS: We selected 15 types of patient safety targets for our systematic review. We searched the literature published between 2000 and 2010 using the following terms: "costs and cost analysis," "cost-effectiveness," "cost," and "financial management, hospital." We appraised the methodologic quality of potentially relevant studies using standard economic methods. We recorded results in the original currency, adjusted for inflation, and then converted to 2010 US dollars for comparative purposes (2010 US$1.00 = 2010 €0.76). The quality of each costing study per patient safety target was also evaluated. RESULTS: We screened 1948 abstracts, and identified 158 potentially eligible studies, of which only 61 (39%) reported any costing methodology. In these 61 studies, we found wide estimates of the attributable costs of patient safety events ranging from $2830 to $10,074. In general hospital populations, the cost per case of hospital-acquired infection ranged from $2132 to $15,018. Nosocomial bloodstream infection was associated with costs ranging from $2604 to $22,414. CONCLUSION: There are wide variations in the estimates of economic burden due to differences in study methods and methodologic quality. Greater attention to methodologic standards for economic evaluations in patient safety is needed.

Comparative economic analyses of patient safety improvement strategies in acute care: a systematic review.

BACKGROUND: The objective was to systematically review comparative economic analyses of patient safety improvements in the acute care setting. METHODS: A systematic review of 15 patient safety target conditions and six improvement strategies was conducted. The authors searched the published literature through Medline (2000-November 2011) using the following search terms for costs: 'costs and cost analysis', 'cost-effectiveness', 'cost' and 'financial management, hospital'. The methodological quality of potentially relevant studies was appraised using Cochrane rules of evidence for clinical effectiveness in quality improvement, and standard economic methods. RESULTS: The authors screened 2151 abstracts, reviewed 212 potentially eligible studies, and identified five comparative economic analyses that reported a total of seven comparisons based on at least one clinical effectiveness study of adequate methodological quality. Pharmacist-led medication reconciliation to prevent potential adverse drug events dominated (lower costs, better safety) a strategy of no reconciliation. Chlorhexidine for vascular catheter site care to prevent catheter-related bloodstream infections dominated a strategy of povidone-iodine for catheter site care. The Keystone ICU initiative to prevent central line-associated bloodstream infections was economically dominant over usual care. Detecting surgical foreign bodies using standard counting compared with a strategy of no counting had an incremental cost of US$1500 (CAN$1676) for each surgical foreign body detected. Several safety improvement strategies were less economically attractive, such as bar-coded sponges for reducing retained surgical sponges compared with standard surgical counting, and giving erythropoietin to reduce transfusion requirements in critically ill patients to avoid one transfusion-related adverse event. CONCLUSIONS: Five comparative economic analyses were found that reported a total of seven comparisons based on at least one effectiveness study of adequate methodological quality. On the basis of these limited studies, pharmacist-led medication reconciliation, the Keystone ICU intervention for central line-associated bloodstream infections, chlorhexidine for vascular catheter site care, and standard surgical sponge counts were economically attractive strategies for improving patient safety. More comparative economic analyses of such strategies are needed.

Incidence of toxic epidermal necrolysis and Stevens-Johnson Syndrome in an HIV cohort: an observational, retrospective case series study.

BACKGROUND: The incidence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) has been reported to be between 0.95 and 1 per 1000 individuals with AIDS. Accessibility to a cohort of individuals with HIV with known drug exposure (including drug, dose, and time of exposure) and collection of adverse-event information may provide an opportunity to determine an incidence rate of SJS and TEN. OBJECTIVE: The primary objective of this analysis was to determine the incidence of confirmed SJS and TEN in a cohort of Canadian HIV patients who were receiving HIV and HIV-related medications. STUDY DESIGN: This was a retrospective analysis of an HIV cohort. PATIENT POPULATION: The Ontario HIV Treatment Network (OHTN) cohort population was eligible for this analysis. METHODS: A search of the OHTN database was conducted to determine whether cases with a diagnosis of SJS or TEN were included. Search terms included 'TEN,' 'SJS,' 'epidermal necrolysis,' and 'erythema multiforme.' All SJS and TEN cases recorded in the OHTN database between January 1995 and August 2008 were obtained. Diagnostic criteria for SJS and TEN were established and two reviewers examined the medical records to confirm the SJS or TEN diagnosis. Drug exposure and utilization were documented. Incidence rates for the entire cohort were calculated. RESULTS: Seventeen cases over seven OHTN study sites were identified from an approximate cohort sample size of 3700. There were 15 men (88%). The mean ± SD age was 51.6 ± 11.3 years and time since HIV diagnosis was 16.1 ± 4.4 years. Only one patient reported experiencing a previous SJS or TEN episode. Of the 17 cases, clinical experts diagnosed five cases as true SJS and/or TEN, two cases were labeled as indeterminant, and the remaining cases were considered not SJS or TEN. Among the confirmed cases, drugs taken included nevirapine, trimethoprim/sulfamethoxazole (cotrimoxazole), stavudine (d4T), and clarithromycin. CONCLUSIONS: The incidence of SJS and/or TEN was 5-7 per 3710 or approximately 1-2 per 1000 individuals in this cohort with HIV. Careful diagnosis of this adverse event is required for an accurate measure of incidence and to avoid false inflation of the incidence.