Derivation and internal validation of the multivariate toxigenic C. difficile diarrhea model and risk score for emergency room and hospitalized patients with diarrhea.

Background: Many factors have been associated with the risk of toxigenic C. difficile diarrhea (TCdD). This study derived and internally validated a multivariate model for estimating the risk of TCdD in patients with diarrhea using readily available clinical factors. Methods: A random sample of 3,050 symptomatic emergency department or hospitalized patients undergoing testing for toxigenic C. difficile at a single teaching hospital between 2014 and 2018 was created. Unformed stool samples positive for both glutamate dehydrogenase antigen by enzyme immunoassay and tcdB gene by polymerase chain reaction were classified as TCdD positive. The TCdD Model was created using logistic regression and was modified to the TCdD Risk Score to facilitate its use. Results: 8.1% of patients were TCdD positive. TCdD risk increased with abdominal pain (adjusted odds ratio 1.3; 95% CI, 1.0-1.8), previous C. difficile diarrhea (2.5, 1.1-6.1), and prior antibiotic exposure, especially when sampled in the emergency department (4.2, 2.5-7.0) versus the hospital (1.7, 1.3-2.3). TCdD risk also increased when testing occurred earlier during the hospitalization encounter, when age and white cell count increased concurrently, and with decreased eosinophil count. In internal validation, the TCdD Model had moderate discrimination (optimism-corrected C-statistic 0.65, 0.62-0.68) and good calibration (optimism-corrected Integrated Calibration Index [ICI] 0.017, 0.001-0.022). Performance decreased slightly for the TCdD Risk Score (C-statistic 0.63, 0.62-0.63; ICI 0.038, 0.004-0.038). Conclusions: TCdD risk can be predicted using readily available clinical risk factors with modest accuracy.

Development of the multivariate administrative data cystectomy model and its impact on misclassification bias.

BACKGROUND: Misclassification bias (MB) is the deviation of measured from true values due to incorrect case assignment. This study compared MB when cystectomy status was determined using administrative database codes vs. predicted cystectomy probability. METHODS: We identified every primary cystectomy-diversion type at a single hospital 2009-2019. We linked to claims data to measure true association of cystectomy with 30 patient and hospitalization factors. Associations were also measured when cystectomy status was assigned using billing codes and by cystectomy probability from multivariate logistic regression model with covariates from administrative data. MB was the difference between measured and true associations. RESULTS: 500 people underwent cystectomy (0.12% of 428 677 hospitalizations). Sensitivity and positive predictive values for cystectomy codes were 97.1% and 58.6% for incontinent diversions and 100.0% and 48.4% for continent diversions, respectively. The model accurately predicted cystectomy-incontinent diversion (c-statistic [C] 0.999, Integrated Calibration Index [ICI] 0.000) and cystectomy-continent diversion (C:1.000, ICI 0.000) probabilities. MB was significantly lower when model-based predictions was used to impute cystectomy-diversion type status using for both incontinent cystectomy (F = 12.75; p < .0001) and continent cystectomy (F = 11.25; p < .0001). CONCLUSIONS: A model using administrative data accurately returned the probability that cystectomy by diversion type occurred during a hospitalization. Using this model to impute cystectomy status minimized MB. Accuracy of administrative database research can be increased by using probabilistic imputation to determine case status instead of individual codes.

Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing Risks: Evidence From 12 Randomized Trials.

BACKGROUND: Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit. METHODS: We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHA2DS2-VASc) and then again using a competing risk model that uses the same inputs as CHA2DS2-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy. RESULTS: A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHA2DS2-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; P<0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA2DS2-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%). CONCLUSIONS: VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHA2DS2-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.

Introduction of a penicillin allergy de-labelling program with direct oral challenge and its effects on utilization of beta-lactam antimicrobials: a multicenter retrospective parallel cohort study.

BACKGROUND: Self-reported penicillin allergy labels are common and often inaccurate after assessment. These labels can lead to reduced use of first-line beta-lactam antibiotics and worse outcomes. We measured the impact of a previously performed inpatient proactive systematic penicillin allergy de-labelling program on subsequent antibiotic use. This prior program included assessment, risk-stratification, and low risk direct oral amoxicillin challenge. METHODS: We performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses in Ottawa, Canada across two penicillin de-labelling intervention periods across April 15th to April 30th, 2021, and February 15th to March 8th, 2022. Outcomes, including penicillin allergy labelling and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics and multivariate regression analyses were performed. RESULTS: A total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention groups had sustained penicillin allergy label removal at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p < 0.001). In the 6-months following admission, beta-lactams were prescribed more frequently in the intervention groups vs. the non-intervention groups for all patients (28 [16.1%] vs.15 [7.7%], p = 0.04) and were prescribed more frequently amongst those who received at least one antibiotic (28/46 [60.9%] vs.15/40 [37.5%], p = 0.097). In a multivariate regression analysis, the intervention groups were found to be associated with an increased odds of beta-lactam prescribing in all patients (OR 2.49, 95%CI 1.29-5.02) and in those prescribed at least one antibiotic (OR 2.44, 95%CI 1.00-6.15). No drug-related adverse events were reported. CONCLUSIONS: Proactive penicillin allergy de-labelling for inpatients was associated with a reduction in penicillin allergy labels and increased utilization of beta-lactams in the subsequent 6-months.

Resource utilization and cost assessment of a proactive penicillin allergy de-labeling program for low-risk inpatients.

BACKGROUND: Resource utilization and costs can impede proactive assessment and de-labeling of penicillin allergy among inpatients. METHODS: Our pilot intervention was a proactive penicillin allergy de-labeling program for new inpatients with penicillin allergy. Patients deemed appropriate for a challenge with a low-risk penicillin allergy history were administered 250 mg amoxicillin and monitored for 1 h. We performed an explorative economic evaluation using various healthcare professional wages. RESULTS: Over two separate 2-week periods between April 2021 and March 2022, we screened 126 new inpatients with a penicillin allergy. After exclusions, 55 were appropriate for formal assessment. 19 completed the oral challenge, and 12 were directly de-labeled, resulting in a number needed to screen of 4 and a number needed to assess of 1.8 to effectively de-label one patient. The assessor's median time in the hospital per day de-labeling was 4h08 with a range of (0h05, 6h45). A single-site annual implementation would result in 715 penicillin allergy assessments with 403 patients de-labeled assuming 20,234 annual weekday admissions and an 8.9% penicillin allergy rate. Depending on the assessor used, the annual cost of administration would be between $21,476 ($53.29 per effectively de-labeled patient) for a pharmacy technician and $61,121 ($151.67 per effectively de-labeled patient) for a Nurse Practitioner or Physician Assistant. CONCLUSION: A proactive approach, including a direct oral challenge for low-risk in-patients with penicillin allergy, appears safe and feasible. Similar programs could be implemented at other institutions across Canada to increase access to allergy assessment.

Outcomes following coronary artery bypass grafting with multiple arterial grafting by pump status in men and women.

BACKGROUND: Multiple arterial grafting (MAG) and off-pump surgery are strategies proposed to improve outcomes with coronary artery bypass grafting (CABG). This study was conducted to determine the impact of off-pump surgery on outcomes after CABG with MAG in men and women. METHODS: This cohort study used population-based data to identify all Ontarians undergoing isolated CABG with MAG between October 2008 and September 2019. The primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiac and cerebrovascular events (MACCE; hospitalization for stroke, myocardial infarction hospitalization or heart failure, or repeat revascularization). Analysis used propensity-score overlap-weighted cause-specific Cox proportional hazard regression. RESULTS: A total of 2989 women (1188 off-pump, 1801 on-pump) and 16,209 men (6065 off-pump, 10,144 on-pump) underwent MAG with a median follow-up of 5.0 years (interquartile range, 2.7-8.0) years. Compared to the on-pump approach, all-cause mortality was not changed with off-pump status (hazard ratio [HR] in women: 1.25 [95% CI, 0.83-1.88]; in men: 1.08 [95% CI, 0.85-1.37]). In women, the risk of MACCE was significantly higher off-pump (HR, 1.45; 95% CI, 1.04-2.03), with nonsignificantly increased risk observed for all component outcomes. CONCLUSIONS: In patients undergoing CABG with MAG, this population-based analysis found no association between pump status and survival in either men or women. However, it did suggest that off-pump MAG in women may be associated with an increased risk of MACCE.

Derivation and External Validation of the Ottawa Bloodstream Infection Model for Acutely Ill Adults.

BACKGROUND: Knowing the probability that patients have a bloodstream infection (BSI) could influence the ordering of blood cultures and interpretation of their preliminary results. Many previous BSI probability models have limited applicability and accuracy. This study used currently recommended modeling techniques and a large sample to derive and validate the Ottawa BSI Model. METHODS: At a tertiary care teaching hospital, we retrieved a random sample of 4180 adults having blood cultures in our emergency department or during the initial 48 h of the encounter. Variable selection was based on clinical experience and a systematic review of previous model performance. Model performance was measured in a temporal external validation group of 4680 patients. RESULTS: A total of 327 derivation patients had a BSI (8.0%). BSI risk increased with increased number of culture sets (2 sets: adjusted odds ratio [aOR] 1.52 [1.10-2.11]; 3 sets: 1.99 [0.86-4.58]); with indwelling catheter (aOR 2.07 [1.34-3.20); with increasing temperature, heart rate, and neutrophil-lymphocyte ratio; and with decreasing systolic blood pressure, platelet count, urea-creatinine ratio, and estimated glomerular filtration rate. In the temporal external validation group, model discrimination was good (c-statistic 0.71 [0.69-0.74]) and calibration was very good (integrated calibration index .016 [.010-.024]). Exclusion of validation patients with acute SARS-CoV-2 infection improved discrimination slightly (c-statistic 0.73 [0.69-0.76]). CONCLUSIONS: The Ottawa BSI Model uses commonly available data to return an expected BSI probability for acutely ill patients. However, it cannot exclude BSI and its complexity requires computational assistance to use.

Validity of two weight prediction models for community-living patients participating in a weight loss program.

Models predicting individual body weights over time clarify patient expectations in weight loss programs. The accuracy of two commonly used weight prediction models in community living people is unclear. All eligible people entering a weight management program between 1992 and 2015 were included. Patients' diet was 1200 kcal/day for week 0 followed by 900 kcal/day for weeks 1-7 and were excluded from the analysis if they were nonadherent. We generated expected weights using the National Institutes of Health Body Weight Planner (NIH-BWP) and the Pennington Biomedical Research Center Weight Loss Predictor (PBRC-WLP). 3703 adherent people were included (mean age 46 years, 72.6% women, mean [SD] weight 262.3 pounds [54.2], mean [SD] BMI 42.4 [7.6]). Mean (SD) relative body weight differences (100*[observed-expected]/expected) for NIH-BWP and PBRC-WLP models was - 1.5% (3.8) and - 2.9% (3.2), respectively. At week 7, mean squared error with NIH-BWP (98.8, 83%CI 89.7-108.8) was significantly lower than that with PBRC-WLP (117.7, 83%CI 112.4-123.4). Notable variation in relative weight difference were seen (for NIH-BWP, 5th-95th percentile was - 6.2%, + 3.7%; Δ 9.9%). During the first 7 weeks of a weight loss program, both weight prediction models returned expected weights that were very close to observed values with the NIH-BWP being more accurate. However, notable variability between expected and observed weights in individual patients were seen. Clinicians can monitor patients in weight loss programs by comparing their progress with these data.

Barriers and facilitators to participation in exercise prehabilitation before cancer surgery for older adults with frailty: a qualitative study.

BACKGROUND: Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. METHODS: This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. RESULTS: Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. CONCLUSIONS: Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions.

The Independent Association of Plasma and Red Blood Cell Zinc Concentrations with Long-Term Outcomes of Hospitalized Patients.

Background: Plasma and RBC zinc values are unrelated in hospitalized patients. The independent association of these values with important patient outcomes is unknown. Objectives: Measure the independent association of plasma and RBC zinc with outcomes in hospitalized patients. Methods: Plasma and RBC zinc concentrations were prospectively measured within 48 h of hospitalization in consenting patients. Data were linked deterministically with population-based health administrative data to measure each association of zinc measures with 2 outcomes (time to death from any cause and likelihood of death or urgent readmission to hospital within 30-d of discharge) after adjusting for validated outcome risk scores. Results: In total, 250 people admitted to medical services were studied. Patients were ill with a 1-y baseline expected death risk (IQR) of 19.9% (6.3%-37.2%). The observed 1-y and 2-y all-cause death risks were 24.5% (95% CI: 19.6%, 30.3%) and 33.2% (95% CI: 27.3%, 39.9%), respectively. Death risk increased significantly as plasma zinc concentrations decreased (P = 0.0001). This association persisted even after adjusting for the baseline expected death risk (P = 0.02) with every 2-µmol/L decrease in plasma zinc concentrations being independently associated with, on average, a 35% increase in the death risk. RBC zinc concentrations were not associated with the death risk. Neither plasma nor RBC zinc concentrations were significantly associated with the 30-d death or urgent readmission rate. Conclusions: Plasma, but not RBC, zinc concentrations are independently associated with the all-cause death risk in hospitalized medical patients. Further study is required to determine whether this association is causal and identify its potential causal pathways. Curr Dev Nutr 2023;x:xx.

Predictive Models for Kidney Recovery and Death in Patients Continuing Dialysis as Outpatients after Starting in Hospital.

BACKGROUND: For patients who initiate dialysis during a hospital admission and continue to require dialysis after discharge, outpatient dialysis management could be improved by better understanding the future likelihood of recovery to dialysis independence and the competing risk of death. METHODS: We derived and validated linked models to predict the subsequent recovery to dialysis independence and death within 1 year of hospital discharge using a population-based cohort of 7657 patients in Ontario, Canada. Predictive variables included age, comorbidities, length of hospital admission, intensive care status, discharge disposition, and prehospital admission eGFR and random urine albumin-to-creatinine ratio. Models were externally validated in 1503 contemporaneous patients from Alberta, Canada. Both models were created using proportional hazards survival analysis, with the "Recovery Model" using Fine-Gray methods. Probabilities generated from both models were used to develop 16 distinct "Recovery and Death in Outpatients" (ReDO) risk groups. RESULTS: ReDO risk groups in the derivation group had significantly distinct 1-year probabilities for recovery to dialysis independence (first quartile: 10% [95% confidence interval (CI), 9% to 11%]; fourth quartile: 73% [70% to 77%]) and for death (first quartile: 12% [11% to 13%]; fourth quartile: 46% [43% to 50%]). In the validation group, model discrimination was modest (c-statistics [95% CI] for recovery and for death quartiles were 0.70 [0.67 to 0.73] and 0.66 [0.62 to 0.69], respectively), but calibration was excellent (integrated calibration index [95% CI] was 7% [5% to 9%] and 4% [2% to 6%] for recovery and death, respectively). CONCLUSIONS: The ReDO models generated accurate expected probabilities of recovery to dialysis independence and death in patients who continued outpatient dialysis after initiating dialysis in hospital. An online tool on the basis of the models is available at https://qxmd.com/calculate/calculator_874 .

Overestimation of anticoagulant benefit in patients with atrial fibrillation and low life expectancy: evidence from 12 randomized trials.

Background: Patients with atrial fibrillation (AF) have a high rate of all-cause mortality that is only partially attributable to vascular outcomes. While the competing risk of death may affect expected anticoagulant benefit, guidelines do not account for it. We sought to determine if using a competing risks framework materially affects the guideline-endorsed estimate of absolute risk reduction attributable to anticoagulants. Methods: We conducted a secondary analysis of 12 RCTs that randomized patients with AF to oral anticoagulants or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of anticoagulants to prevent stroke or systemic embolism using two methods. First, we estimated the ARR using a guideline-endorsed model (CHA 2 DS 2 -VASc) and then again using a Competing Risk Model that uses the same inputs as CHA 2 DS 2 -VASc but accounts for the competing risk of death and allows for non-linear growth in benefit over time. We compared the absolute and relative differences in estimated benefit and whether the differences in estimated benefit varied by life expectancy. Results: 7933 participants had a median life expectancy of 8 years (IQR 6, 12), determined by comorbidity-adjusted life tables. 43% were randomized to oral anticoagulation (median age 73 years, 36% women). The guideline-endorsed CHA 2 DS 2 -VASc model estimated a larger ARR than the Competing Risk Model (median ARR at 3 years, 6.9% vs. 5.2%). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA 2 DS 2 -VASc model - Competing Risk Model 3-year risk) was -1.2% (42% relative underestimation); for those with life expectancies in the lowest decile, 3-year ARR difference was 5.9% (91% relative overestimation). Conclusion: Anticoagulants were exceptionally effective at reduced stroke risk. However, anticoagulant benefits were misestimated with CHA 2 DS 2 -VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced in patients with the lowest life expectancy and when benefit was estimated over a multi-year horizon.

Frequency and Type of Outpatient Visits for Patients With Cardiovascular Ambulatory-Care Sensitive Conditions During the COVID-19 Pandemic and Subsequent Outcomes: A Retrospective Cohort Study.

Background Because the impact of changes in how outpatient care was delivered during the COVID-19 pandemic is uncertain, we designed this study to examine the frequency and type of outpatient visits between March 1, 2019 to February 29, 2020 (prepandemic) and from March 1, 2020 to February 28, 2021 (pandemic) and specifically compared outcomes after virtual versus in-person outpatient visits during the pandemic. Methods and Results Population-based retrospective cohort study of all 3.8 million adults in Alberta, Canada. We examined all physician visits and 30- and 90-day outcomes, with a focus on those adults with the cardiovascular ambulatory-care sensitive conditions heart failure, hypertension, and diabetes. Our primary outcome was emergency department visit or hospitalization, evaluated using survival analysis accounting for competing risk of death. Although in-person outpatient visits decreased by 38.9% in the year after March 1, 2020 (10 142 184 versus 16 592 599 in the prior year), the introduction of virtual visits (7 152 147; 41.4% of total) meant that total outpatient visits increased by 4.1% in the first year of the pandemic for Albertan adults. Outpatient visit frequency (albeit 41.4% virtual, 58.6% in-person) and prescribing patterns were stable in the first year after pandemic onset for patients with the cardiovascular ambulatory-care sensitive conditions we examined, but laboratory test frequency declined by 20% (serum creatinine) to 47% (glycosylated hemoglobin). In the first year of the pandemic, virtual outpatient visits were associated with fewer subsequent emergency department visits or hospitalizations (compared with in-person visits) for patients with heart failure (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.85-0.96] at 30 days and 0.96 [95% CI, 0.92-1.00] at 90 days), hypertension (aHR, 0.88 [95% CI, 0.85-0.91] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days), or diabetes (aHR, 0.90 [95% CI, 0.87-0.93] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days). Conclusions The adoption and rapid uptake of virtual outpatient care during the COVID-19 pandemic did not negatively impact frequency of follow-up, prescribing, or short-term outcomes, and could have potentially positively impacted some of these for adults with heart failure, diabetes, or hypertension in a setting where there was an active reimbursement policy for virtual visits. Given declines in laboratory monitoring and screening activities, further research is needed to evaluate whether long-term outcomes will differ.

Guideline-Concordant Antibiotic Therapy for the Hospital Treatment of Community-Acquired Pneumonia and 1-Year All-Cause and Cardiovascular Mortality in Older Adult Patients Surviving to Discharge.

BACKGROUND: Selection of empiric antibiotic treatment for community-acquired pneumonia (CAP) that is concordant with clinical practice guidelines has been associated with improved short-term outcomes of this infection, but whether it is also associated with longer-term outcomes is unknown. RESEARCH QUESTION: Is guideline-concordance of the initial antibiotic treatment given to older adult patients hospitalized with CAP associated with the 1-year all-cause and cardiovascular mortality risk of those patients who survive hospitalization for this infection? STUDY DESIGN AND METHODS: A total of 1,909 older (> 65 years of age) patients were identified who survived hospitalization for CAP at The Ottawa Hospital (Ontario, Canada) between 2004 and 2015. Linking patients' information to hospital and provincial data sets, this study analyzed whether the selection of the initial antibiotic therapy for their CAP was concordant with current clinical practice guidelines, and whether guideline-concordance was associated with 1-year all-cause and cardiovascular mortality following their index CAP hospitalization. Adjustments were made for the patients' overall 1-year expected death risk; CAP severity; and history of previous pneumonia admissions, myocardial infarction, heart failure, or cerebrovascular disease. RESULTS: Selection of guideline-concordant antibiotic therapy was associated with a trend towards lower all-cause mortality at 1 year post-CAP (hazard ratio, 0.82; 95% CI, 0.65-1.04; P = .099). Furthermore, the use of guideline-concordant antibiotic therapy was associated with a significant almost 50% reduction in cardiovascular death risk 1 year following CAP admission (hazard ratio, 0.53; 95% CI, 0.34-0.80; P = .003). INTERPRETATION: Use of guideline-concordant antibiotic therapy for CAP treatment in older hospitalized patients is associated with a significant reduction in the risk of cardiovascular death at 1 year post-CAP. This finding further supports current clinical practice guideline recommendations for CAP treatment.

Imputing missing laboratory results may return erroneous values because they are not missing at random.

BACKGROUND AND OBJECTIVES: Regression models incorporating laboratory tests treat unordered tests as missing and are often imputed. Imputation typically assumes that data are "missing at random" (MAR, test's order status is unrelated to its result after accounting for other variables). This study examined the validity of this assumption. METHODS: We included 14 biochemistry tests. All tests were measured regardless of test order status. Test-stratified multiple linear regression determined the independent association between test result and order status after adjusting for patient age, sex, comorbidities, and patient location. Testing likelihood models were created for all tests using hospital-wide data. RESULTS: Four hundred thirty-four patients were included (mean age [standard deviation] 60.7 [19.1], 50.5% female). In 9 of 14 tests (64.2%), test results were significantly associated with order status after adjustment. Results were significantly more abnormal when tests were ordered for 6 tests and significantly more normal for 3 tests. Test abnormality increased as testing likelihood decreased. CONCLUSIONS: These data suggest that laboratory data are often not MAR. The direction and extent of differences in missing laboratory test values varies between tests. Overall the abnormality of ordered tests increased as testing likelihood decreased. These results suggest that imputating missing laboratory data may return biased values.

The Network Relative Model Accuracy (NeRMA) Score can quantify the relative accuracy of prediction models in concurrent external validations.

BACKGROUND: Network meta-analysis (NMA) quantifies the relative efficacy of three or more interventions from trials evaluating some, but usually not all, treatments. This study applied the analytical approach of NMA to quantify the relative accuracy of prediction models with distinct patient applicability that are evaluated on the same population ('concurrent external validation'). METHODS: We simulated binary events in 5000 patients using a known risk function. We biased the risk function and modified its precision by pre-specified amounts to create 15 prediction models with varying accuracy and distinct patient applicability. Prediction model accuracy was measured using the Scaled Brier Score (SBS). Overall prediction model accuracy was measured using fixed-effects methods accounting for distinct model applicability patterns. Prediction model accuracy was summarized as the Network Relative Model Accuracy (NeRMA) Score which increases as models become more accurate and ranges from <0 (model less accurate than random guessing) through 0 (accuracy of random guessing) to 1 (most accurate model in concurrent external validation). RESULTS: The unbiased prediction model had the highest SBS. The NeRMA score correctly ranked all simulated prediction models by the extent of bias from the known risk function. A SAS macro and R-function was created and available to implement the NeRMA Score. CONCLUSIONS: The NeRMA Score makes it possible to quantify the relative accuracy of binomial prediction models with distinct applicability in a concurrent external validation.

Concurrent external validation of bloodstream infection probability models.

OBJECTIVE: Accurately estimating the likelihood of bloodstream infection (BSI) can help clinicians make diagnostic and therapeutic decisions. Many multivariate models predicting BSI probability have been published. This study measured the performance of BSI probability models within the same patient sample. METHODS: We retrieved validated BSI probability models included in a recently published systematic review that returned a patient-level BSI probability for adults. Model applicability, discrimination, and accuracy was measured in a simple random sample of 4485 admitted adults having blood cultures ordered in the emergency department or the initial 48 hours of hospitalization. RESULTS: Ten models were included (publication years 1991-2015). Common methodological threats to model performance included overfitting and continuous variable categorization. Restrictive inclusion criteria caused seven models to apply to <15% of validation patients. Model discrimination was less than originally reported in derivation groups (median c-statistic 60%, range 48-69). The observed BSI risk frequently deviated from expected (median integrated calibration index 4.0%, range 0.8-12.4). Notable disagreement in expected BSI probabilities was seen between models (median (25th-75th percentile) relative difference between expected risks 68.0% (28.6-113.6%)). DISCUSSION: In a large randomly selected external validation population, many published BSI probability models had restricted applicability, limited discrimination and calibration, and extensive inter-model disagreement. Direct comparison of model performance is hampered by dissimilarities between model-specific validation groups.

Primary Preventive Care of Hematopoietic Stem Cell Transplantation Survivors: Time to Educate and Empower Recipients and Providers.

Increasing use of hematopoietic stem cell transplantation (HCT) and improvements in recipient outcomes have led to a steady increase in the number of allogeneic HCT survivors. In addition to complications specific to the transplantation process, HCT recipients are at increased risk of developing cardiovascular disease (CVD) and subsequent neoplasm (SN). Strict surveillance of risk factors for CVD and cancer in the general population is recommended as an essential component of long-term follow-up (LTFU) care of HCT survivors, but implementation of this has been suboptimal. Various models for improving the provision of survivorship care have been proposed, including a hybrid/combined care approach wherein the HCT provider manages transplantation-specific complications and the primary care physician (PCP) provides general medical care, including surveillance and aggressive management of CVD risk factors and screening for SN. This model also offers a practical approach to LTFU care for HCT survivors who live at a distance from the HCT center, which is a reality for many recipients of HCT at The Ottawa Hospital (TOH). As the success of such a hybrid approach to survivorship care depends on the engagement of HCT recipients with their PCP and compliance with recommended general population surveillance, the aim of the present study was to assess the rates of PCP attendance and adherence to recommended preventive medicine interventions in the years immediately before and after HCT. We hypothesized that rates would be suboptimal and planned to use these results as a baseline for an educational initiative aimed at increasing awareness of HCT recipients and their PCPs about embracing preventive survivorship care. This was a single-center cohort study of allogeneic HCT recipients who underwent transplantation at TOH with linkage to population-based health administrative data. Published clinical practice guidelines were used to define recommended screening for CVD risk factors and cancer. The rates of annual PCP visits and utilization of recommended preventive care interventions in the 5 years before and after HCT were calculated for all eligible patients. Between 2014 and 2020, 409 patients with provincial health care coverage underwent allogeneic HCT at TOH. The median patient age was 51 years (range, 15 to 73 years), with a male predominance (60.9%). Approximately one-quarter of recipients did not attend a PCP visit in the 5 years before and after transplantation, and this proportion increased to one- third in the fifth year post-HCT. Among those recipients who were eligible, only 20% to 25% underwent recommended screening for dyslipidemia and diabetes. Cancer screening rates were also low, at 16% to 18% for cervical cancer, 18% to 22% for colon cancer, and 30% to 31% for breast cancer. These results highlight the need to increase awareness of HCT recipients and their PCPs about the risk of developing CVD and SN post-transplantation and to emphasize the potential to mitigate this risk by adhering to recommendations for surveillance to enable prompt intervention. Patient education should incorporate this information and empower HCT survivors to actively engage in their follow-up care and optimize their long-term outcomes.

Positive Predictive Value of Primary Subarachnoid Hemorrhage Diagnoses on Death Certificates.

PURPOSE: Epidemiological studies of primary subarachnoid hemorrhage (pSAH) frequently include population-based death registries for case finding. The positive predictive value of pSAH diagnoses in death registries is unknown. METHODS: This cross-sectional study identified all people in Ontario, Canada with pSAH listed as a cause of death between 2013 and 2017. pSAH was classified as "very likely" if diagnosis of pSAH was confirmed by autopsy, there was a previous hospitalization where pSAH probability exceeded 85% or death was preceded within a week by an emergency room visit where pSAH probability exceeded 25%. pSAH was classified as "very unlikely" if previous cerebrovascular imaging had never been done. Remaining cases were classified as "pSAH status unknown". RESULTS: 1,613 deaths attributed to pSAH were identified (mean 322/year). pSAH classification frequencies were as follows: very likely 528 (32.7%); very unlikely 433 (26.8%); and status unknown 652 (40.4%). CONCLUSION: We found that a quarter of pSAH cases in our province's death registry were very unlikely to be true pSAH while 40% had unknown veracity. These data should be considered when using death registries for pSAH case finding.

Relationship between Plasma Zinc and Red Blood Cell Zinc Levels in Hospitalized Patients.

BACKGROUND: Patient zinc stores are quantified with plasma or red blood cell (RBC) measures. The relationship between these 2 measures of zinc status has not been determined in a broad population of hospitalized patients. METHODS: Both plasma zinc and RBC zinc were prospectively collected and measured in 252 consenting patients admitted urgently to hospital. Plasma and RBC zinc levels were measured within 48 h of admission. We collected demographic, vitals, and laboratory data for use in multivariate regression models that included markers of acute disease severity and systemic inflammation. RESULTS: Plasma zinc and RBC zinc levels were low in 63% and 10% of hospitalized patients, respectively. Categorized zinc levels based on normal intervals for plasma and RBC zinc values were not related (χ2 0.47 [2 df] P = 0.79). The Pearson correlation coefficient between plasma zinc and RBC zinc was -0.09 (P = 0.15). After adjustments for multiple clinical covariates, the correlation coefficient remained insignificant (r = -0.11, P = 0.08). Plasma zinc was inversely associated with markers of inflammation including the neutrophil-to-lymphocyte ratio and temperature. CONCLUSIONS: Patient-specific plasma and RBC zinc are unrelated in hospitalized patients, possibly due to decreased values with acute illness seen in the former but not the latter. Future studies are required to determine which of these measures best predicts outcomes in hospitalized patients.