Association of Preoperative Anticholinergic Medication Exposure With Postoperative Healthcare Resource Use and Outcomes: A Population-based Cohort Study.

OBJECTIVE: The aim of this study was to measure the association of preoperative anticholinergic exposure with length of stay (LOS) and other outcomes in older people having elective noncardiac surgery. SUMMARY BACKGROUND DATA: Anticholinergic medications are associated with adverse events in nonsurgical populations; the association of anticholinergic medications with outcomes in elective surgery patients is poorly described. METHODS: We conducted a retrospective, population-based cohort study using linked administrative data in Ontario, Canada. We identified all people >65 years old, from 2003 to 2014, having major, elective noncardiac surgery. Anticholinergic medication exposure was quantified using the Anticholinergic Risk Scale (ARS). Multilevel, multivariable modeling measured the adjusted association of ARS with LOS (primary outcome), institutional discharge, readmissions, costs, and survival (secondary outcomes). RESULTS: Of 245,410 individuals, 71,569 had anticholinergic exposure (ARS 1-2, 15.6%; ARS ≥3, 13.6%). Median LOS was 5 days (interquartile range 3-7). Using proportional hazards analysis to model time to discharge, adjusting for in-hospital death as a competing risk, and surgical risk, demographic characteristics, and comorbidities, higher ARS scores were associated with longer LOS [smaller hazard ratios (HRs) mean longer LOS; ARS 1-2: adjusted HR 0.94, 95% confidence interval (CI), 0.93-0.95, P < 0.0001; ARS ≥3: adjusted HR 0.93, 95% CI, 0.91-0.95, P < 0.0001]. Similar associations were observed for all secondary outcomes. CONCLUSIONS: Increasing ARS scores were associated with increased LOS, decreased survival, higher rates of institutional discharge and readmission, and higher costs of care. Perioperative interventional research to reduce the anticholinergic exposure in older surgical patients is likely warranted.

Derivation and Validation of a Generalizable Preoperative Frailty Index Using Population-based Health Administrative Data.

OBJECTIVE: To develop and validate a preoperative frailty index (pFI) for use in population-based health administrative (HA) data. SUMMARY BACKGROUND DATA: Frailty is a robust predictor of adverse postoperative outcomes. Population-level frailty measures used in surgical studies have significant methodological limitations. Frailty indices (FIs) are a well-defined approach to measuring frailty with well-described methods for development and evaluation. An appropriate preoperative FI in HA data has not been derived or evaluated. METHODS: Retrospective cohort study using linked HA data in Canada. We identified people >65 years (2002-2015) who had major elective or emergency surgery. Standardized methods were used to construct a 30-variable pFI. Unadjusted and multilevel, multivariable adjusted models were used to measure the association of the pFI with 1-year mortality and institutional discharge. Elective patients were the derivation cohort, emergency patients were the validation cohort. Prespecified sensitivity analyses were performed. RESULTS: We identified 415,704 elective, and 95,581 emergency patients. The elective 1-year mortality rate was 4.7%. Thirty percent of population-level deaths occurred in people with frailty. Every 0.1-unit increase in the pFI was associated with a 2.20-fold increase in the adjusted odds of mortality (95% CI 2.15-2.26; c-statistic 0.81), and a 1.70-fold increase in institutional discharge (95% CI 1.59-1.80; c-statistic 0.71). pFI performance was similar in emergency patients, and was robust to changes in index composition. CONCLUSIONS: A preoperative FI derived from HA data is a robust method to measure frailty in elective and emergency patients. Generalizable FIs should be considered a standard approach to population-level study of surgical frailty.

Association of Polypharmacy with Survival, Complications, and Healthcare Resource Use after Elective Noncardiac Surgery: A Population-based Cohort Study.

BACKGROUND: Polypharmacy is increasingly prevalent in older patients and is associated with adverse events among medical patients. The impact of polypharmacy on outcomes after elective surgery is poorly described. The authors' objective was to measure the association of polypharmacy with survival, complications, and resource use among older patients undergoing elective surgery. METHODS: After registration (NCT03133182), the authors identified all individuals older than 65 yr old having their first elective noncardiac surgery in Ontario, Canada, between 2002 and 2014. Using linked administrative data, the authors identified all prescriptions dispensed in the 90 days before surgery and classified people receiving five or more unique medications with polypharmacy. The associations of polypharmacy with 90-day survival (primary outcome), complications, length of stay, costs, discharge location, and readmissions were estimated after multilevel, multivariable adjustment for demographics, comorbidities, previous healthcare use, and surgical factors. Prespecified and post hoc sensitivity analyses were also performed. RESULTS: Of 266,499 patients identified, 146,026 (54.8%) had polypharmacy. Death within 90 days occurred in 4,356 (3.0%) patients with polypharmacy and 1,919 (1.6%) without (adjusted hazard ratio = 1.21; 95% CI, 1.14 to 1.27). Sensitivity analyses demonstrated no increase in effect when only high-risk medications were considered and attenuation of the effect when only prescriptions filled in the 30 preoperative days were considered (hazard ratio = 1.07). Associations were attenuated or not significant in patients with frailty and higher comorbidity scores. CONCLUSIONS: Older patients with polypharmacy represent a high-risk stratum of the perioperative population. However, the authors' findings call into question the causality and generalizability of the polypharmacy-adverse outcome association that is well documented in nonsurgical patients.

Long-term survival and resource use in critically ill cardiac surgery patients: a population-based study.

PURPOSE: Most cardiac surgery patients recover well; a substantial minority become critically ill after surgery. The epidemiology of critical illness after cardiac surgery is poorly described. We measured the association of prolonged critical illness with long-term survival and resource use after cardiac surgery. METHODS: This was a historical population-based cohort study in Ontario, Canada (2002-2013), of adult cardiac surgery patients. Validated methods were used to measure postoperative intensive care unit (ICU) length of stay (LOS). We categorized patients into short (0-2 day), moderate (3-9 day), and long (10+ day) ICU LOS groups. The adjusted associations of ICU LOS with one-year survival (primary outcome) and costs, hospital readmissions, and institutional discharge were measured using multilevel, multivariable regression. Pre-specified sensitivity analyses were performed. RESULTS: We included 111,740 patients having their first cardiac surgery during the study period who survived ≥ ten postoperative days. Most patients had a short ICU LOS (75.9%); 20.9% and 3.3% had moderate or long ICU LOS, respectively. The short-stay one-year mortality rate was 2.1%. Longer ICU LOS was independently associated with decreased one-year survival (moderate LOS: hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.6 to 1.94; long LOS: HR, 8.66; 95% CI, 7.93 to 9.44). Sensitivity analyses supported the findings of the primary analysis. Secondary outcomes were independently associated with longer ICU LOS. Long ICU LOS patients occupied 30% of all ICU bed days, and 55% died or were discharged to an institution. CONCLUSION: Prolonged ICU LOS after cardiac surgery is associated with decreased 1-year survival and increased healthcare resource use.

Long-term Outcomes of Patients Surgically Treated for Hirschsprung Disease.

BACKGROUND: The only curative treatment for Hirschsprung disease (HD) is surgical repair. However, some patients experience poor postoperative outcomes. We determined long-term outcomes of all HD patients in Ontario, Canada's most populous province. METHODS: We conducted a retrospective cohort study including all children with HD born between April 1, 1991 and March 31, 2014 in Ontario using linked health administrative data. Each HD case was matched to five non-HD controls on sex, date of birth, region of residence and income and followed to March 31, 2016. Chronic diarrhea and constipation were identified using combinations of outpatient physician billing codes in both HD patients and non-HD residents of the province. We determined risk factors associated with diarrhea and constipation, including surgery type and sociodemographic characteristics, using multivariable conditional logistic regression, and reported adjusted odds ratios (aORs). RESULTS: There were 3,265,172 children born in the study period, of whom 673 had HD. Compared to controls, chronic constipation was more common in HD patients (27.5% versus 2.1%; aOR 17.2, 95% CI 12.6 to 23.4), as was chronic diarrhea (29.9% versus 6.9%, aOR 5.22, 95% CI 4.19 to 6.50). In HD patients, older age at surgery was associated with increased risk of chronic constipation (OR 2.71, 95% CI 1.75 to 4.20). Surgery type, sex, rural/urban residence and income were not associated with risk of chronic constipation or diarrhea. CONCLUSION: Chronic constipation and diarrhea were common following surgery for HD. Older age at surgery was associated with subsequent risk of chronic constipation. Surgery type was not associated with increased risk of chronic constipation or diarrhea.

Association between newborn screening analytes and hypoxic ischemic encephalopathy.

Hypoxic ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. Our study sought to examine whether patterns of newborn screening analytes differed between infants with and without neonatal HIE in order to identify opportunities for potential use of these analytes for diagnosis in routine clinical practice. We linked a population-based newborn screening registry with health databases to identify cases of HIE among term infants (≥37 weeks' gestation) in Ontario from 2010-2015. Correlations between HIE and screening analytes were examined using multivariable logistic regression models containing clinical factors and individual screening analytes (acyl-carnitines, amino acids, fetal-to-adult hemoglobin ratio, endocrine markers, and enzymes). Among 731,841 term infants, 3,010 were diagnosed with HIE during the neonatal period. Multivariable models indicated that clinical variables alone or in combination with hemoglobin values were not associated with HIE diagnosis. Although the model was improved after adding acyl-carnitines and amino acids, the ability of the model to identify infants with HIE was moderate. Our findings indicate that analytes associated with catabolic stress were altered in infants with HIE; however, future research is required to determine whether amino acid and acyl-carnitine profiles could hold clinical utility in the early diagnosis or clinical management of HIE. In particular, further research should examine whether cord blood analyses can be used to identify HIE within a clinically useful timeframe or to guide treatment and predict long-term health outcomes.

Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease.

INTRODUCTION: Metabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors. METHODS: We conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD) or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured. RESULTS: CKD occurred in 2086 (0.16%, median time 612 days) and dialysis in 641 (0.05%, median time 99 days) infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09). This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days. CONCLUSION: Routinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors.

Effect of Preoperative Geriatric Evaluation on Outcomes After Elective Surgery: A Population-Based Study.

BACKGROUND/OBJECTIVES: Randomized and nonrandomized single-center studies suggest that preoperative geriatric evaluation improves postoperative outcomes in older adults. The generalizability and population-level effect of preoperative geriatric evaluation has not been determined. Our objective was to measure the adjusted association between preoperative geriatric evaluation and postoperative outcomes. DESIGN: Multilevel multivariable regression model analysis of a population-based historical cohort. SETTING: Publicly funded universal healthcare system in Ontario, Canada. PARTICIPANTS: All adults aged 65 and older having major, elective, noncardiac surgery from 2002 to 2014 (N = 266,499). INTERVENTION: We studied geriatric consultations and comprehensive assessments performed in the 4 months prior to surgery. These were identified using validated methods. MEASUREMENTS: Ninety-day survival (primary outcome), in-hospital complications, length of stay, 30-day readmissions, need for supported discharge, and 90-day costs of care. RESULTS: The 7,352 participants (2.8%) who had a preoperative geriatric evaluation had longer 90-day survival than those who who did not (adjusted hazard ratio = 0.81, 95% confidence interval = 0.68-0.95). Length of stay and complication rates did not differ between groups, but participants evaluated by a geriatrician preoperatively had higher rates of supported discharge, readmission rates, and costs of care. Sensitivity analyses supported the association between preoperative geriatric assessment and 90-day survival. CONCLUSION: In individuals aged 65 and older undergoing major, elective, noncardiac surgery, preoperative geriatric evaluation was associated with longer 90-day survival, but it is used infrequently. Given these results, and those of previous small studies, the influence of a geriatric evaluation on postoperative outcomes should be determined in a multicenter randomized trial.

Validation of algorithms to determine incidence of Hirschsprung disease in Ontario, Canada: a population-based study using health administrative data.

OBJECTIVE: Incidence rates of Hirschsprung disease (HD) vary by geographical region, yet no recent population-based estimate exists for Canada. The objective of our study was to validate and use health administrative data from Ontario, Canada to describe trends in incidence of HD between 1991 and 2013. STUDY DESIGN: To identify children with HD we tested algorithms consisting of a combination of diagnostic, procedural, and intervention codes against the reference standard of abstracted clinical charts from a tertiary pediatric hospital. The algorithm with the highest positive predictive value (PPV) that could maintain high sensitivity was applied to health administrative data from April 31, 1991 to March 31, 2014 (fiscal years 1991-2013) to determine annual incidence. Temporal trends were evaluated using Poisson regression, controlling for sex as a covariate. RESULTS: The selected algorithm was highly sensitive (93.5%) and specific (>99.9%) with excellent predictive abilities (PPV 89.6% and negative predictive value >99.9%). Using the algorithm, a total of 679 patients diagnosed with HD were identified in Ontario between 1991 and 2013. The overall incidence during this time was 2.05 per 10,000 live births (or 1 in 4,868 live births). The incidence did not change significantly over time (odds ratio 0.998, 95% confidence interval 0.983-1.013, p = 0.80). CONCLUSION: Ontario health administrative data can be used to accurately identify cases of HD and describe trends in incidence. There has not been a significant change in HD incidence over time in Ontario between 1991 and 2013.

Using newborn screening analytes to identify cases of neonatal sepsis.

Neonatal sepsis is associated with high mortality and morbidity, yet challenges with available diagnostic approaches can lead to delays in therapy. Our study assessed whether newborn screening analytes could be utilized to identify associations with neonatal sepsis. We linked a newborn screening registry with health databases to identify cases of sepsis among infants born in Ontario from 2010-2015. Correlations between sepsis and screening analytes were examined within three gestational age groups (early preterm: <34 weeks; late preterm: 34-36 weeks; term: ≥37 weeks), using multivariable logistic regression models. We started with a model containing only clinical factors, then added groups of screening analytes. Among 793,128 infants, 4,794 were diagnosed with sepsis during the neonatal period. Clinical variables alone or in combination with hemoglobin values were not strongly predictive of neonatal sepsis among infants born at term or late preterm. However, model fit improved considerably after adding markers of thyroid and adrenal function, acyl-carnitines, and amino acids. Among infants born at early preterm gestation, neither clinical variables alone nor models incorporating screening analytes adequately predicted neonatal sepsis. The combination of clinical variables and newborn screening analytes may have utility in identifying term or late preterm infants at risk for neonatal sepsis.

Incidence of Hospitalization for Respiratory Syncytial Virus Infection amongst Children in Ontario, Canada: A Population-Based Study Using Validated Health Administrative Data.

IMPORTANCE: RSV is a common illness among young children that causes significant morbidity and health care costs. OBJECTIVE: Routinely collected health administrative data can be used to track disease incidence, explore risk factors and conduct health services research. Due to potential for misclassification bias, the accuracy of data-elements should be validated prior to use. The objectives of this study were to validate an algorithm to accurately identify pediatric cases of hospitalized respiratory syncytial virus (RSV) from within Ontario's health administrative data, estimate annual incidence of hospitalization due to RSV and report the prevalence of major risk factors within hospitalized patients. STUDY DESIGN AND SETTING: A retrospective chart review was performed to establish a reference-standard cohort of children from the Ottawa region admitted to the Children's Hospital of Eastern Ontario (CHEO) for RSV-related disease in 2010 and 2011. Chart review data was linked to Ontario's administrative data and used to evaluate the diagnostic accuracy of algorithms of RSV-related ICD-10 codes within provincial hospitalization and emergency department databases. Age- and sex-standardized incidence was calculated over time, with trends in incidence assessed using Poisson regression. RESULTS: From a total of 1411 admissions, chart review identified 327 children hospitalized for laboratory confirmed RSV-related disease. Following linkage to administrative data and restriction to first admissions, there were 289 RSV patients in the reference-standard cohort. The best algorithm, based on hospitalization data, resulted in sensitivity 97.9% (95%CI: 95.5-99.2%), specificity 99.6% (95%CI: 98.2-99.8%), PPV 96.9% (95%CI: 94.2-98.6%), NPV 99.4% (95%CI: 99.4-99.9%). Incidence of hospitalized RSV in Ontario from 2005-2012 was 10.2 per 1000 children under 1 year and 4.8 per 1000 children aged 1 to 3 years. During the surveillance period, there was no identifiable increasing or decreasing linear trend in the incidence of hospitalized RSV, hospital length of stay and PICU admission rates. Among the Ontario RSV cohort, 16.3% had one or more major risk factors, with a decreasing trend observed over time. CONCLUSION: Children hospitalized for RSV-related disease can be accurately identified within population-based health administrative data. RSV is a major public health concern and incidence has not changed over time, suggesting a lack of progress in prevention.