Population-based outpatient antimicrobial use in Newfoundland and Labrador: a retrospective descriptive study.

BACKGROUND: Data that have been reported on antimicrobial use in Newfoundland and Labrador (NL) do not appear to be representative of use at the population level. We sought to use pharmacy network data on prescriptions to describe outpatient antimicrobial use in NL. METHODS: We analyzed all outpatient antimicrobial prescriptions dispensed between June 1, 2017, and June 8, 2021, from the provincial pharmacy network database and translated deidentified data into SPSS. We excluded prescriptions for parenteral and topical antimicrobials, antivirals and antifungals. We described antimicrobial use using the prescription rate and defined daily dose (DDD) rate. RESULTS: Overall, we analyzed 1 586 534 prescriptions dispensed to 394 708 people by 3431 prescribers. The rate of antimicrobial use was 741 prescriptions per 1000 population per year (7161 DDD/1000 population/yr). The median duration of prescriptions was 7 (interquartile range 7-10) days. The prescription rate decreased from 867 to 546 per 1000 population per year (-37%) over the study period, and the mean DDD rate decreased from 8387 to 5356 DDD per 1000 population per year (-36.1%). Antimicrobials with the highest DDD rate were amoxicillin (1568 DDD/1000/yr), doxycycline (864 DDD/1000/yr) and ciprofloxacin (633 DDD/1000/yr). Prescribers wrote a mean of 102 (standard deviation 248) prescriptions per year; 3 prescribers wrote more than 2500 prescriptions per year. Overall, 9203 (2.3%) of the 394 708 people in the study population received 4 or more prescriptions per year. INTERPRETATION: The rate of antimicrobial use in NL is lower than previously described in national surveillance data. Potential targets for stewardship intervention include prolonged duration of prescriptions, high-rate prescribers and high-rate patients, but further research is needed to assess the appropriateness of prescriptions according to diagnosis.

The 2018 Global Point Prevalence Survey of antimicrobial consumption and resistance in 47 Canadian hospitals: a cross-sectional survey.

BACKGROUND: Patient-level surveillance of antimicrobial use (AMU) in Canadian hospitals empowers the reduction of inappropriate AMU and was piloted in 2017 among 14 hospitals in Canada. We aimed to describe AMU on the basis of patient-level data in Canadian hospitals in 2018 in terms of antimicrobial prescribing prevalence and proportions, antimicrobial indications, and agent selection in medical, surgical and intensive care wards. METHODS: Canadian adult, pediatric and neonatal hospitals were invited to participate in the standardized web-based cross-sectional Global Point Prevalence Survey of Antimicrobial Consumption and Resistance (Global-PPS) conducted in 2018. An identified site administrator assigned all wards admitting inpatients to specific surveyors. A physician, pharmacist or nurse with infectious disease training performed the survey. The primary outcomes were point prevalence rates for AMU over the study period regarding prescriptions, indications and agent selection in medical, surgical and intensive care wards. The secondary outcomes were AMU for resistant organisms and practice appropriateness evaluated on the basis of quality indicators. Antimicrobial consumption is presented in terms of prevalence and proportions. RESULTS: Forty-seven of 118 (39.8%) hospitals participated in the survey; 9 hospitals were primary care centres, 15 were secondary care centres and 23 were tertiary or specialized care centres. Of 13 272 patients included, 33.5% (n = 4447) received a total of 6525 antimicrobials. Overall, 74.1% (4832/6525) of antimicrobials were for therapeutic use, 12.6% (n = 825) were for medical prophylaxis, 8.9% (n = 578) were for surgical prophylaxis, 2.2% (n = 143) were for other use and 2.3% (n = 147) were for unidentified reasons. A diagnosis or indication was documented in the patient's file at the initiation for 87.3% (n = 5699) of antimicrobials; 62.9% (n = 4106) of antimicrobials had a stop or review date; and 72.0% (n = 4697) of prescriptions were guided by local guidelines. INTERPRETATION: Overall, three-quarters of AMU was for therapeutic use across participating hospitals. Canadian hospitals should be further incentivized to create and adapt local guidelines on the basis of recent antimicrobial resistance data.

Impact of a mobile decision support tool on antimicrobial stewardship indicators in St. John's, Canada.

OBJECTIVES: Inappropriate antibiotic use contributes to antimicrobial resistance. The SpectrumTM app provides antibiotic decision support, based on local antimicrobial resistance rates. We determined the impact of regional implementation of the app on inpatient antimicrobial appropriateness, inpatient antimicrobial usage (AMU), population-based Clostridioides difficile infection (CDI) rates and cost, using a retrospective, before and after quasi-experimental design, including a one-year study period. METHODS: The SpectrumTM app was released to prescribers in February, 2019. We performed two one-day inpatient point prevalence surveys using the National Antimicrobial Prescribing Survey tool, six months before (June 25, 2018) and six months after (June 25, 2019) app dissemination. Inpatient AMU in Defined Daily Dose/1000 patient days and CDI incidence were compared, before and after app dissemination. RESULTS: The pre-survey included 184 prescriptions, and the post-survey included 197 prescriptions. Appropriateness was 97/176 (55.1%) pre, and 126/192 (65.6%) post (+10.5%, p = 0.051). Inpatient AMU declined by 6.6 DDD/1000 patient days per month, and CDI declined by 0.3 cases per month. Cost savings associated with reduced AMU were $403.98/bed/year and associated with reduced CDI were $82,078/year. CONCLUSION: We observed improvement in antimicrobial stewardship indicators following SpectrumTM implementation. We cannot determine the cause of these improvements.

Impact of lipid-lowering medications and low-density lipoprotein levels on 1-year clinical outcomes after coronary artery bypass grafting.

BACKGROUND: Studies investigating lipid-lowering medication (LLM) use and LDL levels in coronary artery bypass grafting patients are limited. STUDY DESIGN: The Veterans Affairs Randomized On/Off Bypass Trial's patient records were analyzed for LLM use and 1-year LDL levels. Mortality, acute MI (AMI), and repeat revascularization rates were compared at 1 year between patients with and without LLM at discharge. In addition, AMI, repeat revascularization, and graft patency were compared between patients that did and did not achieve a 1-year LDL target level of <100 mg/dL. RESULTS: The LLM data were available for 86.4% (1,904 of 2,203) of patients. Rates of LLM use were 83.4% (1,316 of 1,577) at discharge and 90.0% (1,713 of 1,904) at 1 year. Patients discharged after coronary artery bypass grafting on LLMs had a significantly lower 1-year mortality rate (1.9% vs 5.4%; p < 0.01) than those not discharged on LLM, and 1-year AMI and repeat revascularization rates were not significantly different. Of the patients with 1-year LDL measurements, 69.4% (1,200 of 1,729) achieved an LDL target level of <100 mg/dL. No differences were seen in AMI, revascularization, or graft occlusion rates between patients who achieved target LDL levels and those who did not. CONCLUSIONS: Rates of LLM use among veterans post-coronary artery bypass grafting are high. Discharge on LLM might be associated with improved intermediate-term survival. Patients who achieved an LDL target of <100 mg/dL at 1-year did not experience improved 1-year clinical outcomes or graft patency. Longer-term follow-up might reveal differences in cardiac outcomes related to achievement of target LDL levels.

On-pump versus off-pump coronary-artery bypass surgery.

BACKGROUND: Coronary-artery bypass grafting (CABG) has traditionally been performed with the use of cardiopulmonary bypass (on-pump CABG). CABG without cardiopulmonary bypass (off-pump CABG) might reduce the number of complications related to the heart-lung machine. METHODS: We randomly assigned 2203 patients scheduled for urgent or elective CABG to either on-pump or off-pump procedures. The primary short-term end point was a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) before discharge or within 30 days after surgery. The primary long-term end point was a composite of death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction within 1 year after surgery. Secondary end points included the completeness of revascularization, graft patency at 1 year, neuropsychological outcomes, and the use of major resources. RESULTS: There was no significant difference between off-pump and on-pump CABG in the rate of the 30-day composite outcome (7.0% and 5.6%, respectively; P=0.19). The rate of the 1-year composite outcome was higher for off-pump than for on-pump CABG (9.9% vs. 7.4%, P=0.04). The proportion of patients with fewer grafts completed than originally planned was higher with off-pump CABG than with on-pump CABG (17.8% vs. 11.1%, P<0.001). Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group (82.6% vs. 87.8%, P<0.01). There were no treatment-based differences in neuropsychological outcomes or short-term use of major resources. CONCLUSIONS: At 1 year of follow-up, patients in the off-pump group had worse composite outcomes and poorer graft patency than did patients in the on-pump group. No significant differences between the techniques were found in neuropsychological outcomes or use of major resources. (ClinicalTrials.gov number, NCT00032630.).

Does preoperative hemoglobin independently predict short-term outcomes after coronary artery bypass graft surgery?

BACKGROUND: The role of preoperative hemoglobin in predicting short-term coronary artery bypass graft (CABG) surgery outcomes has not been well established. This study investigated the association between preoperative hemoglobin level with 30-day operative mortality and perioperative complications. METHODS: For the period from 1997 to 2005, the Department of Veterans Affairs Continuous Improvement in Cardiac Surgery Program database was used to extract 36,658 CABG-only deidentified records for patients undergoing cardiopulmonary bypass. Univariate and multivariate statistical models were used to predict both mortality and morbidity outcomes for varying levels of hemoglobin. RESULTS: Unadjusted odds of 30-day operative mortality for patients with preoperative hemoglobin level less than 10 g/dL were 2.37 times higher than for patients with hemoglobin levels of 10 g/dL or greater (95% confidence interval: 1.84 to 3.05; p < 0.0001). Multivariable effect upon 30-day operative mortality decreased considerably (odds ratio = 1.29, 95% confidence interval: 0.99 to 1.68; p = 0.064). CONCLUSIONS: As several risk factors may occur concurrently with low hemoglobin, preoperative hemoglobin level less than 10 g/dL was not a strong independent predictor of 30-day operative mortality or perioperative morbidity in multivariate models for on-pump CABG-only patients. Hemoglobin and serum creatinine were correlated, with creatinine exhibiting the stronger association with mortality. These findings suggest that moderate or severe anemia may be intertwined with other risk factors, such as serum creatinine or congestive heart failure. For a CABG patient subgroup presenting with a complex clinical preoperative profile, therefore, risk-model approaches may be inherently limited in separately identifying the predictors of anemic patients' outcomes.

Improving quality of care in cardiac surgery: evaluating risk factors, processes of care, structures of care, and outcomes.

The 1985 release of hospital report cards by the Health Care Financing Administration awakened the public's awareness of variations in outcomes following patient treatment. In 1972, the Department of Veterans Affairs initiated an oversight process for all VA-based cardiac surgery programs. In response to Public Law 99-166, the Continuous Improvement in Cardiac Surgery Program (CICSP) national database was developed in 1987. This CICSP effort reported variations in outcomes across VA cardiac programs. In 1997, the CICSP expanded (CICSP-X) to identify the interrelationships of risk factors with processes and structures of care, as well as clinical outcomes. Based on VA findings to date, these quality improvement endeavors appear to have positively affected short-term and longer-term cardiac surgical outcomes. To advance a new patient-focused paradigm for continuous improvement in cardiac surgical care quality for all US citizens, an integrated data-driven reporting approach with broad-based participation should be implemented to optimally improve patient care.

A study design to assess the safety and efficacy of on-pump versus off-pump coronary bypass grafting: the ROOBY trial.

BACKGROUND: Since the late 1960s, coronary artery bypass graft (CABG-only) procedures were traditionally performed using a heart-lung machine on an arrested heart (on-pump). Over the past decade, an increasing number CABG-only procedures were performed on a beating heart (off-pump). Advocates of the off-pump approach expect to reduce many of the adverse side effects related to using the heart-lung machine, while advocates for the on-pump procedure raise concerns related to graft patency rates and long-term event-free survival for the off-pump technique. PURPOSE: The U.S. Department of Veteran Affairs (VA) Cooperative Studies Program funded a randomized, multicenter clinical trial comparing the clinical and resource-related outcomes following on-pump versus off-pump techniques for veterans undergoing a non-emergent CABG-only procedure. The planning committee was faced with several critically important challenges to assure feasibility of study costs and required sample size; generalizability to non-VA surgical practices; and comparability of clinically meaningful results. These challenges are discussed. METHODS: This study is a prospective, randomized, multicenter, single blinded (patient) clinical trial that compares on-pump and off-pump techniques for veterans requiring non-emergent CABG-only procedures. There will be 2200 patients randomized at 17 VA Medical Centers when the five-year recruitment period ends on 15 April 2007. There are two primary objectives: a short-term objective to assess the immediate impact of the two techniques on 30-day mortality/morbidity and a long-term objective to assess one-year mortality/morbidity. Major secondary outcomes are one-year graft patency rates and change in neuropsychological assessments from baseline to one year. All patients are assessed at 30 days post-surgery or discharge from the hospital, whichever is latest, and at one-year post-surgery. RESULTS: During planning, several key issues had to be decided. These included 1) choosing primary objectives: a short-term (30-day) and a long-term (one-year) objective were chosen; 2) choosing primary outcome measures: composite measures were selected to ensure sufficient end-points; 3) standardization of surgical techniques: minimal standardization required but guidelines and continuing discussions on both techniques provided; 4) establishing criteria for surgeons and residents for participation: surgeons required to have completed 20 off-pump procedures prior to doing study procedures and residents, in presence of study surgeon, capable of doing either procedure; 5) identifying metrics of cognitive dysfunction sensitive to treatment: a neuropshychologist hired who centrally monitors cognitive functioning testing; and 6) blinding participants of surgical procedure: attempt to blind participants. LIMITATIONS: Areas of concern are whether all surgeons sufficiently experienced on the off-pump procedure, should residents have been allowed to do study surgeries, should techniques have been standardized more and were the best neurocognitive tests selected. CONCLUSION: The study design presented allows for a balanced and fair assessment of the on-pump and off-pump CABG procedures across a diversity of clinical outcomes and resource use metrics. Its results have the potential to influence clinical cardiac surgical practice in the future.

Exploring the volume-outcome relationship for off-pump coronary artery bypass graft procedures.

BACKGROUND: The relationship between the surgical case volume and risk-adjusted clinical outcomes has been examined for different surgical specialties. The purpose of this study was to explore the relationship between the off-pump coronary artery bypass graft procedure volumes (OPCABG) with risk-adjusted outcomes within the Department of Veterans Affairs (VA) 44 cardiac surgery programs. METHODS: Based on VA Continuous Improvement in Cardiac Surgery Program data, the results of 5,076 OPCABG surgical procedures performed between October 1998 and September 2003 were analyzed. Hierarchical logistic regression models evaluated the relationship between OPCABG procedure volume with risk-adjusted 30-day operative mortality, perioperative morbidity, and 180-day mortality. Both a hospital's average OPCABG volume per 6-month period and the hospital's most recent 6-month OPCABG volume were examined. RESULTS: Hospital OPCABG average volume in a 6-month period ranged from 0.2 to 47.4 procedures; whereas the most recent 6-month OPCABG hospital volume ranged from 0 to 76 OPCABG per site. No relationship between the volume measures and the outcome variables was found. CONCLUSIONS: We did not find an association between OPCABG volume with short-term mortality, perioperative morbidity, or intermediate-term (180-day) mortality.

Cardiovascular medication use after coronary bypass surgery in patients with renal dysfunction: a national Veterans Administration study.

BACKGROUND: Chronic kidney disease is now recognized as an independent risk factor for cardiovascular events. We sought to determine if cardiovascular medications were utilized less in patients with renal dysfunction following coronary artery bypass grafting (CABG) and if the association of decreased medication use was independent of comorbid conditions. We also examined associations between cardiovascular medication use and mortality at 6 months. METHODS: Data from the National Veterans Adminstration (VA) Continuous Improvement in Cardiac Surgery Program were merged with the national VA pharmacy database. Prescription rates within 6 months of discharge for CABG were obtained for four classes of medicines: beta blockers, lipid-lowering agents, antiplatelet agents, and angiotensin antagonists. Utilization of medications in patients with estimated glomerular filtration rate (GFR) 60 to 90, 30 to 60, and <30 were compared with the reference group of GFR >90. RESULTS: In a retrospective analysis of 19,411 patients, the frequency of nonprescription increased with declining GFR. Decreased utilization for patients with GFR 30 to 60 and <30 remained highly significant after adjustment for age, race, hypertension, diabetes, and prior myocardial infarction. In patients with more advanced renal dysfunction (GFR <60), cardiovascular medication use for all medication classes was associated with survival at 6 months after adjusting for demographic and clinical variables. Cumulative protection was seen with use of medication from each additional class. CONCLUSION: In a large VA population undergoing CABG, renal disease is associated with highly significant decreases in utilization of cardiovascular medications. Nonprescription of medications was associated with adverse outcomes in those with renal dysfunction.

Prescription-filling rates for key medications in Veterans Affairs patients after coronary artery bypass grafting.

PURPOSE: The six-month prescription-filling rates for key secondary-prevention drugs in Department of Veterans Affairs (VA) patients who had undergone coronary artery bypass grafting (CABG) were studied. METHODS: Patient records for elective CABG from April 2000 through March 2002 (divided into four six-month periods) were analyzed. The study population included 8925 CABG-only patients surviving to hospital discharge. For each six-month period and in aggregate, the primary study endpoint was the six-month prescription-filling rate. RESULTS: Across the four six-month periods, prescription-filling rates increased for all categories of medications studied. There were modest progressive increases for lipid-lowering agents, statins, -blockers, angiotensin-converting-enzyme Inhibitors, and angiotensin-receptor blockers. The antithrombotic-filling rate averaged 88.5%. Filling rates for aspirin were much higher than for aspirin alternatives. CONCLUSION: Prescription-filling rates for post-CABG medications in VA facilities were generally high and suggested compliance with guidelines for the prevention of cardiovascular events.

Comparison of short-term mortality risk factors for valve replacement versus coronary artery bypass graft surgery.

BACKGROUND: Risk factors for 30-day operative (short-term) mortality following coronary artery bypass graft (CABG only) procedures are well established. However, little is known about how the risk factors for short-term mortality following valve replacement procedures (with or without a CABG procedure performed) compare with CABG only risk factors. METHODS: Department of Veterans Affairs (VA) records (65,585 records) were collected from October 1991 through March 2001 and analyzed. Risk factors for short-term mortality were compared across three subgroups of patients: CABG only surgery (n = 56,318), aortic valve replacement (AVR) with or without CABG (n = 7450), and mitral valve replacement (MVR) with or without CABG (n = 1817). Multivariable logistic regression analyses were used to compare the relative magnitude of risk for 19 candidate predictor variables across subgroups. RESULTS: Only three patient baseline characteristics differed significantly in magnitude of risk between the procedure groups. Partially or totally dependent functional status significantly increased the risk of short-term mortality for AVR patients (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.29-2.09) and MVR patients (OR 2.21, 95% CI 1.48-3.30), but not for CABG only patients (OR 1.04, 95% CI 0.93-1.16). Conversely, previous heart surgery and New York Heart Association functional class III or IV symptoms conferred greater magnitude of risk for CABG only patients compared with the valve subgroups. CONCLUSIONS: Overall, the risk factors for short-term mortality following valve replacement and CABG surgery appear to be relatively consistent. However, clinicians should be aware of the importance of preoperative functional status as a unique predictor of mortality following valve surgery.

Predictors of cognitive decline following coronary artery bypass graft surgery.

BACKGROUND: A significant number of patients develop cognitive impairment that persists for months following coronary artery bypass grafting (CABG) surgery. Our objectives were to identify patient-related risk factors, processes of care, and the occurrence of any perioperative complications associated with cognitive decline. METHODS: Nine hundred thirty-nine patients enrolled in the Processes, Structures, and Outcomes of Care in Cardiac Surgery study undergoing CABG-only surgery at 14 Veterans Administration medical centers between 1992 and 1996 completed a short battery of cognitive tests at baseline and 6-months post-CABG. The composite cognitive score was based on the sum of errors for each individual item in the battery. Multiple linear regression analyses were used to identify independent predictors of the 6-month composite cognitive score. RESULTS: In multivariable analyses, patient characteristics associated with cognitive decline included cerebrovascular disease (p = 0.009), peripheral vascular disease (p = 0.007), history of chronic disabling neurologic illness (p = 0.016), and living alone (p = 0.049), while the number of years of education (p = 0.001) was inversely related to cognitive decline. After adjustment for baseline patient risk factors, the presence of any postoperative complication(s) (p = 0.001) was also associated with cognitive decline while cardiopulmonary bypass time (p = 0.008) was inversely related to cognitive decline. CONCLUSIONS: Patients with noncoronary manifestations of atherosclerosis, chronic disabling neurologic illness, or limited social support are at risk for cognitive decline after CABG surgery. In contrast, more years of education were associated with less cognitive decline. Preoperative assessment of risk factors identified in this study may be useful when counseling patients about the risk for cognitive decline following CABG surgery.

Variation in mortality risk factors with time after coronary artery bypass graft operation.

BACKGROUND: Differences in mortality risk factor sets during different time periods (eg, short-term versus intermediate-term) after coronary artery bypass grafting have been reported. However, little is known about the time-varying effects of mortality risk factors after the operation. METHODS: We analyzed 11,815 veterans who had coronary artery bypass grafting at any of the 43 Veterans Affairs cardiac surgery centers from October 1997 to September 1999. Time-varying effects of 14 mortality risk factors during the 210 days after coronary artery bypass grafting were evaluated using Cox B-spline regression, which provides an estimate of risk for each variable for each day after operation. RESULTS: Eight variables showed significant time-varying effects after operation. The effect of prior heart operation was very high immediately after operation, but disappeared within 1 week. Three other cardiac variables (prior myocardial infarction, preoperative intraaortic balloon pump, and Canadian Cardiovascular Society anginal class III or IV) also conferred the highest risk on the day of operation and decreased thereafter. In contrast, the four time-varying noncardiac risk variables (age, impaired functional status, chronic obstructive pulmonary disease, and renal dysfunction) showed little or no association with mortality immediately after operation, but had increasing impact during the several months after operation. CONCLUSIONS: A sizable number of mortality risk factors have time-varying effects after coronary artery bypass grafting. Several cardiac risk factors have peak impact immediately after operation but dissipate thereafter. Several noncardiac risk factors confer little risk immediately after operation, but these risks increase during several months. This information may help clinicians focus management strategies for patients during the 7 months after operation.