Quality of life and cost-effectiveness of convalescent plasma compared to standard care for hospitalized COVID-19 patients in the CONCOR-1 trial.

BACKGROUND: The CONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1) trial was a multicenter randomized controlled trial assessing convalescent plasma in hospitalized COVID-19 patients. This study evaluates the cost-effectiveness of convalescent plasma and its impact on quality-of-life to provide insight into its potential as an alternative treatment in resource-constrained settings. METHODS: Individual patient data on health outcomes and resource utilization from the CONCOR-1 trial were used to conduct the analysis from the Canadian public payer's perspective with a time horizon of 30 days post-randomization. Baseline and 30-day EQ-5D-5L were measured to calculate quality-adjusted survival. All costs are presented in 2021 Canadian dollars. The base case assessed the EQ-5D-5L scores of hospitalized inpatients reporting at both timepoints, and a utility score of 0 was assigned for patients who died within 30 days. Costs for all patients enrolled were used. The sensitivity analysis utilizes EQ-5D-5L scores from the same population but only uses costs from this population. RESULTS: 940 patients were randomized: 627 received CCP and 313 received standard care. The total costs were $28,716 (standard deviation, $25,380) and $24,258 ($22,939) for the convalescent plasma and standard care arms respectively. EQ-5D-5L scores were 0.61 in both arms (p = .85) at baseline. At 30 days, EQ-5D-5L scores were 0.63 and 0.64 for patients in the convalescent plasma and standard care arms, respectively (p = .46). The incremental cost was $4458 and the incremental quality-adjusted life day was -0.078. DISCUSSION: Convalescent plasma was less effective and more costly than standard care in treating hospitalized COVID-19.

Moving from intervention management to disease management: a qualitative study exploring a systems approach to health technology assessment in Canada.

OBJECTIVES: Health technology assessment (HTA) traditionally informs decision making for single health technologies, which could lead to ill-informed decisions, suboptimal care, and system inefficiencies. We explored opportunities for conceptualizing the decision space in HTA as a disease management question versus an intervention management question. METHODS: Semistructured interviews were conducted between April 2022 and October 2022 with purposefully selected individuals from national and provincial HTA agencies and related organizations in Canada. We conducted manual line by line coding of data informed by our interview guide and sensitizing concepts from the literature. One author coded the data, and findings were independently verified by a second author who coded a subset of transcripts. RESULTS: Twenty-four invitations were distributed, and eighteen individuals agreed to participate. A disease management approach to HTA was differentiated from traditional approaches as being disease-based, multi-interventional, and dynamic. There was general support for an explicit care pathway approach to HTA by informing discussions around patient choice and suboptimal care, creating a space where decision makers can collaborate on shared objectives, and in setting up a platform for open dialogue about managing high-cost and high-severity diseases. There are opportunities for a care pathway approach to be implemented that build on the strengths of the existing HTA system in Canada. CONCLUSIONS: A disease management approach may enhance the impact of HTA by supporting dynamic decision making that could better inform a proactive, resilient, and sustainable healthcare system in Canada.

Are we enrolling the right patients? A scoping review of external validity and generalizability of clinical trials in bloodstream infections.

BACKGROUND: Having a representative population in randomized clinical trials (RCTs) improves external validity and generalizability of trial results. There are limited data examining differences between RCT-enrolled and real-world populations in bloodstream infections (BSI). OBJECTIVES: We conducted a scoping review aiming to review studies assessing generalizability of BSI RCT populations, to identify sub-groups that have been systematically under-represented and to explore approaches to improve external validity of future RCTs. SOURCES: MEDLINE, Embase, and Cochrane Library databases were searched for terms related to external validity or generalizability, BSI, and clinical trials in papers published up to 1 August 2023. Studies comparing enrolled versus nonenrolled patients, or papers discussing external validity or generalizability in the context of BSI RCTs were included. CONTENT: Sixteen papers were included in the final review. Five compared RCT-enrolled and nonenrolled participants from the same source population. There were significant differences between the two groups in all studies, with nonenrolled patients having a greater comorbidity burden and consistently worse outcomes including mortality. We identified several barriers to improving generalizability of RCT populations and outlined potential approaches to reduce these barriers, such as alternative/simplified consent processes, streamlining eligibility criteria and follow-up procedures, quota-based sampling techniques, and ensuring diversity in site and study team selection. IMPLICATIONS: Study cohorts in BSI RCTs are not representative of the general BSI patient population. As we increasingly adopt large pragmatic trials in infectious diseases, it is important to recognize the importance of maximizing generalizability to ensure that our research findings are of direct relevance to our patients.

Evaluating the use of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in the workup of Staphylococcus aureus bacteraemia: a cost-utility analysis.

OBJECTIVES: The use of positron emission tomography/computed tomography (PET/CT) in the evaluation of patients with Staphylococcus aureus bacteraemia can improve the diagnosis of infectious foci and guide clinical management. We aimed to evaluate the cost-utility of PET/CT among adults hospitalized with Staphylococcus aureus bacteraemia. METHODS: A cost-utility analysis was conducted from the healthcare payer perspective using a probabilistic Markov cohort model assessing three diagnostic strategies: (a) PET/CT in all patients, (b) PET/CT in high-risk patients only, and (c) routine diagnostic workup. Primary outcomes were quality-adjusted life years (QALYs), costs in Canadian dollars, and an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses were conducted to evaluate parameter uncertainty. RESULTS: Routine workup resulted in an average of 16.64 QALYs from the time of diagnosis at a lifetime cost of $209 060/patient. This was dominated by PET/CT in high-risk patients (i.e. greater effectiveness at lower costs) with average 16.88 QALYs at a cost of $199 552. Compared with PET/CT in high-risk patients only, PET/CT for all patients cost on average $11 960 more but resulted in 0.14 more QALYs, giving an incremental cost-effectiveness ratio of $83 500 (cost per additional QALY gained); however, there was a high degree of uncertainty comparing these two strategies. At a willingness-to-pay threshold of $50 000/QALY, PET/CT in high-risk patients was the most cost-effective strategy in 58.6% of simulations vs. 37.9% for PET/CT in all patients. DISCUSSION: Our findings suggest that a strategy of using PET/CT in high-risk patients is more cost-effective than no PET/CT. Randomized controlled trials should be conducted to evaluate the use of PET/CT in different patient groups.

Herpes zoster in older adults in Ontario, 2002-2016: Investigating incidence and exploring equity.

Older adults are at increased risk of herpes zoster (HZ) and post-herpetic neuralgia (PHN) and HZ vaccines are available to help prevent infection. The objective of our study was to provide updated data on incidence of HZ and PHN related to clinical and demographic factors in older adults to inform immunization practices. We conducted a population-based, retrospective cohort study and included all cases of HZ seen in outpatient, emergency department, and hospital settings for adults aged 65 years and over between April 1, 2002 to August 31, 2016 in Ontario, Canada. We calculated the incidence of HZ and PHN, and estimated the proportion within each subgroup that developed PHN. We also assessed incidence by neighbourhood-level income quintile before and after the availability of vaccine for private purchase. The average annual incidence of HZ in any setting was 59.0 per 10,000 older adults, with higher incidence in outpatient as opposed to hospital settings. Incidence was higher in the oldest age groups, females, and those classified as immunocompromised or frail. Relative to the pre-vaccine era, the disparities in incidence of HZ by neighbourhood-level income increased, with higher rates of HZ and PHN seen in those residing in lower income quintiles. Additional prevention efforts should be targeted toward adults who are immunocompromised, frail, and those living in lower socioeconomic quintiles. Future work should assess the impact of the zoster vaccine program with a particular focus on equity in the publicly-funded era.

Ontario COVID-19 assessment centre practices in patient counselling, education, and follow-up care: A provincial survey.

Background: In March 2020, COVID-19 assessment centres were launched across the province of Ontario to facilitate COVID-19 testing outside of emergency departments. We aimed to study the degree to which assessment centres provide education and follow-up care for patients with suspected COVID-19. Methods: We conducted an online survey of Ontario COVID-19 assessment centre directors between September 15 and October 15, 2020. The primary outcomes studied were the types of educational modalities employed and information conveyed, methods and frequency of test result communication, and any follow-up care that was offered. Survey respondents were also asked to provide descriptions of barriers to patient education and test communication. Results: A total of 56 directors (representing 73 assessment centres) completed the survey. The most frequent educational modalities employed were educational handouts (92%), direct in-person counselling (89%), and referral to website (72%). Seventy-one percent of respondents indicated patients with positive test results would be notified, and 61% of respondents indicated that follow-up care would be offered. The most frequently reported barriers to patient education were insufficient time and high volume of tests, while the most frequently reported barriers to communication of test results were difficulty accessing online health portals and high volume of tests. Conclusion: The ability of many assessment centres to provide patient education is limited by both individual patient and system-level factors. Assessment centres may benefit from standardization of educational materials, improved accessibility to test results for patients in marginalized groups, and virtual pathways to facilitate additional counselling and care for individuals who test positive.

Historique : En mars 2020, des centres d'évaluation de la COVID-19 ont été lancés dans la province de l'Ontario afin de favoriser le dépistage de la COVID-19 hors des services d'urgence. Les chercheurs visaient à étudier dans quelle mesure ces centres transmettent de l'information et des soins de suivi aux patients chez qui on présume une COVID-19. Méthodologie : Les chercheurs ont réalisé un sondage en ligne auprès des directeurs des centres d'évaluation de la COVID-19 de l'Ontario entre le 15 septembre et le 15 octobre 2020. Le type de modalités pédagogiques utilisé et d'information transmise, les modes et la fréquence de communication des résultats des tests et les soins de suivi offerts étaient les résultats cliniques primaires à l'étude. Les répondants au sondage ont également été invités à décrire les obstacles à la transmission d'information aux patients et à la communication des résultats. Résultats : Au total, 56 directeurs (représentant 73 centres d'évaluation) ont rempli le sondage. Les principales modalités pédagogiques étaient la remise de document d'information (92 %), des conseils individuels directs (89 %) et l'orientation vers un site Web (72 %). Ainsi, 71 % des répondants ont indiqué que les patients obtenant un résultat positif en étaient avisés, et 61 %, que des soins de suivi seraient offerts. Les principaux obstacles à la transmission d'information aux patients étaient le manque de temps et le volume élevé de tests, tandis que les principaux obstacles à la transmission des résultats étaient la difficulté d'accès aux portails santé en ligne et le volume élevé de tests. Conclusion : La capacité de nombreux centres d'évaluation à transmettre de l'information aux patients est limitée à la fois par des facteurs liés aux patients eux-mêmes et par des facteurs systémiques. Les centres d'évaluation pourraient tirer profit de la standardisation des documents pédagogiques, d'un meilleur accès aux résultats des tests pour les patients de groupes marginalisés et de trajectoires virtuelles pour favoriser la transmission de conseils et de soins supplémentaires aux personnes dont les résultats sont positifs.

Influencing duration of antibiotic therapy: A behavior change analysis in long-term care.

BACKGROUND: Prolonged antibiotic duration of therapy is common in long-term care (LTC) settings and associated with increased risk of harm for residents. To identify potential antibiotic stewardship opportunities aimed at prolonged duration of therapy, this study examined barriers and enablers to using shorter courses of antibiotic therapy in the LTC setting. METHODS: Semistructured interviews were conducted with prescribers in LTC home settings, and a total of 8 LTC clinicians participated in the study. Questions and clinical scenarios explored the factors influencing the decisions of prescribers about duration of therapy. Using the Theoretical Domains Framework, interview data were analyzed deductively. RESULTS: The themes identified that influence duration of antibiotic therapy in LTC were environmental context and resources, knowledge, beliefs about consequences, social influences, and behavioral regulation. Specific concerns described by participants included the perceived lack of evidence to support shorter courses in LTC residents, the misconception that shorter courses could lead to greater rates of resistance, and the strong role of habit and prior experience in selecting antibiotic duration. DISCUSSION: There are several factors affecting antimicrobial duration prescribing behavior aside from the clinical scenario itself. Tackling misconceptions and providing educational support may be helpful approaches. CONCLUSIONS: These findings provide theory-informed evidence to support the development of antimicrobial stewardship interventions aimed at improving duration of antibiotic therapy.

Predictors and variability of antibiotic prescribing amongst family physicians.

BACKGROUND: Rising rates of antimicrobial resistance are driven by overuse of antibiotics. Characterizing physician antibiotic prescribing variability can inform interventions to optimize antibiotic use. OBJECTIVES: To describe predictors of overall antibiotic prescribing as well as the inter-physician variability in antibiotic prescribing amongst family physicians. METHODS: We conducted a 5 year cohort study of antibiotic prescribing rates by family physicians in Ontario, Canada using a repository of electronic medical records. Using multilevel logistic regression models fitted with random intercepts for physicians, we evaluated the association of patient-, physician- and clinic-level characteristics with antibiotic prescribing rates. RESULTS: We included 3956921 physician-patient encounters, 322129 unique patients and 313 physicians from 41 family medicine clinics. Physicians prescribed a median of 54 (interdecile range 28-95) antibiotics per 1000 encounters. Female children aged 3-5 years were most likely to receive antibiotics compared with men ≥65 years (OR 4.01, 95% CI 3.89-4.13). The only significant physician-level predictor was median daily patient visits of ≥20 compared with <10 (OR 1.28, 95% CI 1.06-1.55). The median ORs without and with patient characteristics were 1.68 and 1.69, respectively. Thus, the odds of receiving an antibiotic varied by 1.7-fold for the same patient simply by virtue of encountering two different physicians. CONCLUSIONS: We observed substantial inter-physician variability in antibiotic prescribing that could not be explained by sociodemographic and clinical patient differences, suggesting that risk adjustment of antibiotic prescribing practices may not be required for audit and feedback of family physicians working in similar practice settings.

Comparing prescribing and dispensing databases to study antibiotic use: a validation study of the Electronic Medical Record Administrative data Linked Database (EMRALD).

BACKGROUND: Monitoring and studying community antibiotic use is a critical component in combating rising antimicrobial resistance. OBJECTIVES: To validate an electronic medical record dataset containing antibiotic prescriptions and to quantify some important differences between prescribing and dispensing databases. METHODS: We evaluated antibiotics prescribed and dispensed to patients ≥65 years of age during 2011-15. We compared the EMRALD prescribing database with the validated Ontario Drug Benefit (ODB) dispensing database. Using ODB as the gold standard and limiting to EMRALD physicians, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% CIs. We also compared the relative change in antibiotic use prescribed by all physicians to this population over time between the databases using Poisson regression models. RESULTS: In this population, 74% of all antibiotics dispensed were from non-EMRALD physicians. Trends in use were discordant over time. When we limited ODB to EMRALD prescribers only to assess the validity of EMRALD data, we observed good sensitivity and excellent specificity for correctly identifying antibiotics at 85% (95% CI 84%-85%) and 98% (95% CI 98%-98%), respectively. The PPV was 78% (95% CI 78%-78%) and the NPV was 99% (95% CI 99%-99%). All performance measures were higher among the highest prescribing physicians. CONCLUSIONS: We demonstrated EMRALD is well suited for studying antibiotic prescribing by EMRALD physicians. However, due to the frequency with which patients receive antibiotic prescriptions from their non-primary care physicians, we caution against the use of non-population-based prescribing databases to infer antibiotic use rates or trends over time.

A population-based matched cohort study examining the mortality and costs of patients with community-onset Clostridium difficile infection identified using emergency department visits and hospital admissions.

Few studies have evaluated the mortality or quantified the economic burden of community-onset Clostridium difficile infection (CDI). We estimated the attributable mortality and costs of community-onset CDI. We conducted a population-based matched cohort study. We identified incident subjects with community-onset CDI using health administrative data (emergency department visits and hospital admissions) in Ontario, Canada between January 1, 2003 and December 31, 2010. We propensity-score matched each infected subject to one uninfected subject and followed subjects in the cohort until December 31, 2011. We evaluated all-cause mortality and costs (unadjusted and adjusted for survival) from the healthcare payer perspective (2014 Canadian dollars). During our study period, we identified 7,950 infected subjects. The mean age was 63.5 years (standard deviation = 22.0), 62.7% were female, and 45.0% were very high users of the healthcare system. The relative risk for 30-day, 180-day, and 1-year mortality were 7.32 (95% confidence interval [CI], 5.94-9.02), 3.55 (95%CI, 3.17-3.97), and 2.59 (95%CI, 2.37-2.83), respectively. Mean attributable cumulative 30-day, 180-day, and 1-year costs (unadjusted for survival) were $7,434 (95%CI, $7,122-$7,762), $12,517 (95%CI, $11,687-$13,366), and $13,217 (95%CI, $12,062-$14,388). Mean attributable cumulative 1-, 2-, and 3-year costs (adjusted for survival) were $10,700 (95%CI, $9,811-$11,645), $13,312 (95%CI, $12,024-$14,682), and $15,812 (95%CI, $14,159-$17,571). Infected subjects had considerably higher risk of all-cause mortality and costs compared with uninfected subjects. This study provides insight on an understudied patient group. Our study findings will facilitate assessment of interventions to prevent community-onset CDI.

Influenza A (H1N1pdm09)-Related Critical Illness and Mortality in Mexico and Canada, 2014.

OBJECTIVES: The 2009-2010 influenza A (H1N1pdm09) pandemic caused substantial morbidity and mortality among young patients; however, mortality estimates have been confounded by regional differences in eligibility criteria and inclusion of selected populations. In 2013-2014, H1N1pdm09 became North America's dominant seasonal influenza strain. Our objective was to compare the baseline characteristics, resources, and treatments with outcomes among critically ill patients with influenza A (H1N1pdm09) in Mexican and Canadian hospitals in 2014 using consistent eligibility criteria. DESIGN: Observational study and a survey of available healthcare setting resources. SETTING: Twenty-one hospitals, 13 in Mexico and eight in Canada. PATIENTS: Critically ill patients with confirmed H1N1pdm09 during 2013-2014 influenza season. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were 90-day mortality and independent predictors of mortality. Among 165 adult patients with H1N1pdm09-related critical illness between September 2013 and March 2014, mean age was 48.3 years, 64% were males, and nearly all influenza was community acquired. Patients were severely hypoxic (median PaO2-to-FIO2 ratio, 83 mm Hg), 97% received mechanical ventilation, with mean positive end-expiratory pressure of 14 cm H2O at the onset of critical illness and 26.7% received rescue oxygenation therapy with prone ventilation, extracorporeal life support, high-frequency oscillatory ventilation, or inhaled nitric oxide. At 90 days, mortality was 34.6% (13.9% in Canada vs 50.5% in Mexico, p < 0.0001). Independent predictors of mortality included lower presenting PaO2-to-FIO2 ratio (odds ratio, 0.89 per 10-point increase [95% CI, 0.80-0.99]), age (odds ratio, 1.49 per 10 yr increment [95% CI, 1.10-2.02]), and requiring critical care in Mexico (odds ratio, 7.76 [95% CI, 2.02-27.35]). ICUs in Canada generally had more beds, ventilators, healthcare personnel, and rescue oxygenation therapies. CONCLUSIONS: Influenza A (H1N1pdm09)-related critical illness still predominantly affects relatively young to middle-aged patients and is associated with severe hypoxemic respiratory failure. The local critical care system and available resources may be influential determinants of patient outcome.

The Economic Burden of Hospital-Acquired Clostridium difficile Infection: A Population-Based Matched Cohort Study.

BACKGROUND High-quality cost estimates for hospital-acquired Clostridium difficile infection (CDI) are vital evidence for healthcare policy and decision-making. OBJECTIVE To evaluate the costs attributable to hospital-acquired CDI from the healthcare payer perspective. METHODS We conducted a population-based propensity-score matched cohort study of incident hospitalized subjects diagnosed with CDI (those with the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada code A04.7) from January 1, 2003, through December 31, 2010, in Ontario, Canada. Infected subjects were matched to uninfected subjects (those without the code A04.7) on age, sex, comorbidities, geography, and other variables, and followed up through December 31, 2011. We stratified results by elective and nonelective admissions. The main study outcomes were up-to-3-year costs, which were evaluated in 2014 Canadian dollars. RESULTS We identified 28,308 infected subjects (mean annual incidence, 27.9 per 100,000 population, 3.3 per 1,000 admissions), with a mean age of 71.5 years (range, 0-107 years), 54.0% female, and 8.0% elective admissions. For elective admission subjects, cumulative mean attributable 1-, 2-, and 3-year costs adjusted for survival (undiscounted) were $32,151 (95% CI, $28,192-$36,005), $34,843 ($29,298-$40,027), and $37,171 ($30,364-$43,415), respectively. For nonelective admission subjects, the corresponding costs were $21,909 ($21,221-$22,609), $26,074 ($25,180-$27,014), and $29,944 ($28,873-$31,086), respectively. CONCLUSIONS Hospital-acquired CDI is associated with substantial healthcare costs. To the best of our knowledge, this study is the first CDI costing study to present longitudinal costs. New strategies may be warranted to mitigate this costly infectious disease. Infect Control Hosp Epidemiol 2016;37:1068-1078.

Differential outcome of an antimicrobial stewardship audit and feedback program in two intensive care units: a controlled interrupted time series study.

BACKGROUND: Antimicrobial decision making in intensive care units (ICUs) is challenging. Unnecessary antimicrobials contribute to the development of resistant pathogens, Clostridium difficile infection and drug related adverse events. However, inadequate antimicrobial therapy is associated with mortality in critically ill patients. Antimicrobial stewardship programs are increasingly being implemented to improve antimicrobial prescribing, but the optimal approach in the ICU setting is unknown. We assessed the impact of an audit and feedback antimicrobial stewardship intervention on antimicrobial use, antimicrobial costs, clinical outcomes and microbiologic outcomes in two ICUs with different patient populations. METHODS: The audit and feedback intervention was implemented in a trauma and neurosurgery ICU (TNICU) and a medical surgical ICU (MSICU) at a 465-bed teaching hospital in Toronto, Canada. ICU patients were reviewed Monday to Friday by a physician and pharmacist with infectious diseases training. Recommendations related to appropriate antimicrobial use were presented to ICU teams during a dedicated daily meeting. A controlled interrupted time series analysis was used to compare outcomes in the 12 months before and after the intervention. Cardiovascular and coronary care ICUs served as control units. RESULTS: Mean total monthly antimicrobial use in defined daily doses (DDD) per 1000 patient days was reduced 28% in the TNICU (1433 vs. 1037) but increased 14% in the MSICU (1705 vs. 1936). In the time series analysis, total monthly antimicrobial use in the TNICU decreased by 375 DDD per 1000 patient days (p < 0.0009) immediately following the intervention, followed by a non-significant downward trend in use of -9 DDD per 1000 patient days (p = 0.56). No significant changes in antimicrobial use were identified in the MSICU. Antimicrobial use temporarily increased in one control unit and remained unchanged in the other. There were no changes in mortality, length of stay, readmission rate, incidence of C. difficile infection or resistance patterns of E. coli and P. aeruginosa in either intervention unit. CONCLUSIONS: Audit and feedback antimicrobial stewardship programs can lead to significant reductions in total antimicrobial use in the ICU setting. However, this effect may be context-dependent and further work is needed to determine the ingredients necessary for success.

The economic impact of Clostridium difficile infection: a systematic review.

OBJECTIVES: With Clostridium difficile infection (CDI) on the rise, knowledge of the current economic burden of CDI can inform decisions on interventions related to CDI. We systematically reviewed CDI cost-of-illness (COI) studies. METHODS: We performed literature searches in six databases: MEDLINE, Embase, the Health Technology Assessment Database, the National Health Service Economic Evaluation Database, the Cost-Effectiveness Analysis Registry, and EconLit. We also searched gray literature and conducted reference list searches. Two reviewers screened articles independently. One reviewer abstracted data and assessed quality using a modified guideline for economic evaluations. The second reviewer validated the abstraction and assessment. RESULTS: We identified 45 COI studies between 1988 and June 2014. Most (84%) of the studies were from the United States, calculating costs of hospital stays (87%), and focusing on direct costs (100%). Attributable mean CDI costs ranged from $8,911 to $30,049 for hospitalized patients. Few studies stated resource quantification methods (0%), an epidemiological approach (0%), or a justified study perspective (16%) in their cost analyses. In addition, few studies conducted sensitivity analyses (7%). CONCLUSIONS: Forty-five COI studies quantified and confirmed the economic impact of CDI. Costing methods across studies were heterogeneous. Future studies should follow standard COI methodology, expand study perspectives (e.g., patient), and explore populations least studied (e.g., community-acquired CDI).

Hospital-wide rollout of antimicrobial stewardship: a stepped-wedge randomized trial.

Our objective was to rigorously evaluate the impact of an antimicrobial stewardship audit-and-feedback intervention, via a stepped-wedge randomized trial. An effective intensive care unit (ICU) audit-and-feedback program was rolled out to 6 non-ICU services in a randomized sequence. The primary outcome was targeted antimicrobial utilization, using a negative binomial regression model to assess the impact of the intervention while accounting for secular and seasonal trends. The intervention was successfully transitioned, with high volumes of orders reviewed, suggestions made, and recommendations accepted. Among patients meeting stewardship review criteria, the intervention was associated with a large reduction in targeted antimicrobial utilization (-21%, P = .004); however, there was no significant change in targeted antibiotic use among all admitted patients (-1.2%, P = .9), and no reductions in overall costs and microbiologic outcomes. An ICU day 3 audit-and-feedback program can be successfully expanded hospital-wide, but broader benefits on non-ICU wards may require interventions earlier in the course of treatment.

Determination of tobramycin pharmacokinetics in burn patients to evaluate the potential utility of once-daily dosing in this population.

The objective was to determine the pharmacokinetics of tobramycin in critically ill adult burn patients and evaluate a variety of milligram per kilogram (mg/kg) total body weight (TBW) regimens to determine whether practical initial once-daily administration recommendations to attain desired plasma levels could be identified. A retrospective study was conducted in 58 eligible patients who received tobramycin and had at least one set of steady-state levels from which pharmacokinetic parameters could be determined using standard first-order pharmacokinetic equations. Classification and Regression Tree analysis was used to identify whether tobramycin clearance changed with time postburn. Monte Carlo Simulation was used to evaluate initial mg/kg TBW dosing regimens to determine whether a clinically useful once-daily tobramycin recommendation could be made. Tobramycin clearance was significantly greater for patients ≤45 days postburn vs patients >45 days postburn. Once-daily tobramycin dosing for patients ≤45 days postburn of 10 to 13 mg/kg TBW and for patients >45 days postburn of 8 to 10 mg/kg TBW provided levels similar to those known to be effective in nonburn injury patients. Once-daily tobramycin dosing recommendations for burn patients were determined. Variability in pharmacokinetics in this population and change in pharmacokinetics with time postburn injury necessitate monitoring of tobramycin levels to ensure targets are met and maintained.

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.

The impact of infection on population health: results of the Ontario burden of infectious diseases study.

BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

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.