Effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of acute kidney injury : a clinical research protocol for a substudy of the POISE-3 randomized clinical trial

Background: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. Objective: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. Design: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). Intervention: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients’ mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg. Control: Patients receive their usual antihypertensive medications before and after surgery. The patients’ MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery. Setting: Recruitment from 108 centers in 22 countries from 2018 to 2021. Patients: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications. Measurements: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 μmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization. Methods: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2. Results: Substudy results will be analyzed in 2022. Limitations: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury. Conclusions: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury

Diagnostic accuracy of cystatin C-based eGFR equations at different GFR levels in children

Background and objectives The diagnostic accuracy of cystatin C estimated GFR (eGFR) by various cystatin C equations have varied in different studies. We hypothesized that the GFR level of enrolled patients affects the diagnostic accuracy of a cystatin C equation. Design, setting, participants, & measurements We analyzed 240 consecutively enrolled children at a single Canadian center in a prospective and cross-sectional study. Cystatin C was analyzed with nephelometry, and cystatin C eGFR was estimated by the equations validated in children. GFR was measured by technetium- 99m-diethylene-triamine penta-acetic acid (99mTc DTPA). Results We compared various cystatin C equations across GFR strata \u3c60, \u3c90, ≥135, and ≥150 ml/min per 1.73 m2 for an accurate prediction and appropriate classification of the measured GFR. The CKiD, Zappitelli- CysEq, and Zappitelli-CysCrEq equations had a higher accuracy, estimated by eGFR values within 10% and 30% of the respective 99mTc DTPA, in the GFR categories \u3c60 and \u3c90 ml/min per 1.73 m2, whereas the Bökenkamp, Bouvet, and Filler equations had a greater accuracy in the GFR categories ≥135 and ≥150 ml/min per 1.73 m2. The Bouvet, CKiD, Filler, Zappitelli-CysEq, and Zappitelli-CysCrEq equations had a greater sensitivity to classify GFR \u3c60 and \u3c90 ml/min per 1.73 m2, whereas the Bökenkamp equation had a higher sensitivity for GFR ≥135 and ≥150 ml/min per 1.73 m2. Conclusions The diagnostic accuracy of various cystatin C equations varies with GFR. This issue needs consideration while applying these equations in clinical practice and for further research on eGFR equations. © 2011 by the American Society of Nephrology

Quality of Diabetes Care in Blended Fee-for-Service and Blended Capitation Payment Systems.

OBJECTIVES: In the middle to late 2000s, many family physicians switched from a Family Health Group (FHG; a blended fee-for-service model) to a Family Health Organization (FHO; a blended capitation model) in Ontario, Canada. The evidence on the link between physician remuneration schemes and quality of diabetes care is mixed in the literature. We examined whether physicians who switched from the FHG to FHO model provided better care for individuals living with diabetes relative to those who remained in the FHG model. METHODS: Using longitudinal health administrative data from 2006 to 2016, we investigated the impact of physicians switching from FHG to FHO on 8 quality indicators related to diabetes care. Because FHO physicians are likely to be systematically different from FHGs, we employed propensity-score-based inverse probability-weighted fixed-effects regression models. All analyses were conducted at the physician level. RESULTS: We found that FHO physicians were more likely to provide glycated hemoglobin testing by 2.75% (95% confidence interval [CI], 1.89% to 3.60%), lipid assessment by 2.76% (CI, 1.95% to 3.57%), nephropathy screening by 1.08% (95% CI, 0.51% to 1.66%) and statin prescription by 1.08% (95% CI, 0.51% to 1.66%). Patients under FHOs had a lower estimated risk of mortality by 0.0124% (95% CI, 0.0123% to 0.0126%) per physician per year. However, FHG and FHO physicians were similar for annual eye examination, prescription of angiotensin-converting enzyme inhibitors (or angiotensin II receptor blockers) and patients\u27 risk of avoidable diabetes-related hospitalizations. CONCLUSIONS: Compared with blended fee-for-service, blended capitation payment is associated with a small, but statistically significant, improvement in some aspects of diabetes care

Big Mother or Small Baby: Which Predicts Hypertension?

According to the Barker hypothesis, intrauterine growth restriction and premature delivery adversely affect cardiovascular health in adult life. The association of childhood hypertension as a cardiovascular risk factor and birth weight has been understudied. In a prospective cohort study, the authors evaluated the effect of birth weight, gestational age, maternal prepregnancy body mass index (BMI), and child BMI z score at the time of enrollment on the systolic and diastolic blood pressure (BP) z score in 3024 (1373 women) consecutive outpatient clinic patients aged 2.05 to 18.58 years. The latest National Health and Nutrition Examination Survey (NHANES III) was used to calculate the age-dependent z scores. The median z scores of BMI (+0.48, range -6.96-6.64), systolic BP (+0.41, range -4.50-6.73), and diastolic BP (+0.34, range -3.15-+6.73) were all significantly greater than the NHANES III reference population. Systolic BP z score did not correlate with birth weight or gestational age, but did correlate with maternal prepregnancy BMI (r=090, P\u3c.0001) and BMI z score (r=209, P\u3c.0001). Diastolic BP z score positively correlated with birth weight (0.037, P=044), gestational age (r=052, P=005), BMI z score(r=106, P\u3c.0001), and maternal prepregnancy BMI (r=062, P=0007). In contrast to what would be expected from the Barker hypothesis, the authors found no negative correlation between BP z score and birth weight or gestational age. This study suggests that a high BMI, a big mom, and a high birth weight are more important risk factors for hypertension during childhood than low birth weight or gestational age. © 2010 Wiley Periodicals, Inc

Estimating the prevalence of renal insufficiency in seniors requiring long-term care

Estimating the prevalence of renal insufficiency in seniors requiring long-term care.BackgroundRenal function declines with age, but little is known about the extent of renal insufficiency among the institutionalized elderly. The objective of this study was to estimate the prevalence of low glomerular filtration rate (GFR) in a large sample of elderly adults living in long-term care facilities, and to compare two commonly used methods for estimating GFR.MethodsA total of 9931 residents aged 65years and older participated in a retrospective cross-sectional study of 87 long-term care facilities in Ontario. GFR was estimated by the Cockcroft-Gault and Modification of Diet in Renal Disease Study (MDRD) equations. The prevalence of low GFR, using the Cockcroft-Gault equation (<30mL/min), was compared with the MDRD equation (<30mL/min/1.73m2).ResultsA total of 17.0% (95% CI 15.6 to 18.5) of men and 14.4% (95% CI 13.6 to 15.3) of women had a serum creatinine concentration above the laboratory reported upper reference limit of normal. The prevalence of both elevated serum creatinine and low GFR were observed to increase with age (P < 0.0001). The Cockcroft-Gault equation produced a consistently lower estimate of GFR than did the MDRD equation, a discrepancy most pronounced in the oldest residents. Among all men, a low GFR was more prevalent using the Cockcroft-Gault (10.3%, 95% CI 9.2 to 11.5) than MDRD (3.5%, 95% CI 2.8 to 4.2) equation, with a similar difference also seen in women (23.3%, 95% CI 22.4 to 24.3 versus 4.0%, 95% CI 3.6 to 4.5, respectively). Of all residents whose Cockcroft-Gault estimated GFR was under 30mL/min, 14.7% (95% CI 13.2 to 16.3) were found to have GFR greater than 60mL/min/1.73m2 according to the MDRD equation.ConclusionAge-associated renal impairment is common among elderly long-term care residents, but there exists a clear discrepancy between the Cockcroft-Gault and MDRD equations in predicting GFR. Consideration should be given to medication dose adjustment, based on a practical estimate of GFR. However clarification is needed about which method, if either, is most valid among the frail elderly. Complex patient and societal issues surrounding advanced care directives, treatments associated with renal insufficiency, and, if and when to initiate dialysis, require further attention

Is Prosocial Behavior Associated with Increased Registration for Deceased Organ Donation? A Cross-sectional Study of Ontario, Canada

Background. A community that promotes prosocial behaviors such as organ donor registration or charitable giving could reinforce those behaviors among its residents. Understanding the nature of the relationship between prosocial behaviors at the community level and an individual\u27s decision to engage in prosocial behavior can help in the targeting of communities with lower rates of prosocial activities. The objective of this study was to assess if the likelihood that an individual is a registered deceased organ donor in Ontario, Canada, is associated with community-level charitable giving. Methods. This cross-sectional population-based study involved individual- and community-level data from multiple administrative data sources from ICES and Statistics Canada. To assess the unadjusted and adjusted effects of community-level charitable giving on organ donor registration, we ran 4 sequential multilevel random intercept logistic regression models and used a number of individual- and community-level confounding factors. Results. Statistically significant between-community variance (0.322, SE = 0.020) and interclass correlation coefficient (0.089) suggest that substantial variation in organ donor registration can be attributed to the between-community differences. Community-level charitable giving was correlated with organ donor registration (odds ratios, 1.351; 95% confidence intervals, 1.245-1.466) in the model containing only individual-level confounding factors. However, this relationship became statistically nonsignificant (odds ratios, 0.982; 95% confidence intervals, 907-1.063) when a series of community-level confounding factors were added to the model. Among these confounding factors, individuals\u27 immigration status and community-level ethnic/immigrant concentration had the most pronounced association with organ donor registration. Conclusion. The identification of the characteristics of populations and communities with low organ donor registration rates may inform future initiatives in the area of organ donation awareness and promotion to make them more effective among those particular groups

Atypical antipsychotic medications and hyponatremia in older adults: a population-based cohort study

Background: A number of case reports have suggested a possible association between atypical antipsychotic medications and hyponatremia. Currently, there are no reliable estimates of hyponatremia risk from atypical antipsychotic drugs. Objective: The objective of this study was to examine the 30-day risk of hospitalization with hyponatremia in older adults dispensed an atypical antipsychotic drug relative to no antipsychotic use. Design: The design of this study was a retrospective, population-based cohort study. Setting: The setting of this study was in Ontario, Canada, from 2003 to 2012. Patients: Adults 65 years or older with an identified psychiatric condition who were newly dispensed risperidone, olanzapine, or quetiapine in the community setting compared to adults with similar indicators of baseline health who were not dispensed such a prescription. Measurements: The primary outcome was the 30-day risk of hospitalization with hyponatremia. The tracer outcome (an outcome that is not expected to be influenced by the study drugs) was the 30-day risk of hospitalization with bowel obstruction. These outcomes were assessed using hospital diagnosis codes. Methods: Using health administrative data, we applied a propensity score technique to match antipsychotic users 1:1 to non-users of antipsychotic drugs (58,008 patients in each group). We used conditional logistic regression to compare outcomes among the matched users and non-users. Results: A total of 104 baseline characteristics were well-balanced between the two matched groups. Atypical antipsychotic use compared to non-use was associated with an increased risk of hospitalization with hyponatremia within 30 days (86/58,008 (0.15 %) versus 53/58,008 (0.09 %); relative risk 1.62 (95 % confidence interval (CI) 1.15 to 2.29); absolute risk increase 0.06 % (95 % CI 0.02 to 0.10)). The limited number of events precluded some additional analyses to confirm if the association was robust. Atypical antipsychotic use compared to non-use was not associated with hospitalization with bowel obstruction within 30 days (55/58,008 (0.09 %) versus 44/58,008 (0.08 %); relative risk 1.25 (95 % CI 0.84 to 1.86)). Limitations: We could only study older adults within our data sources. Conclusions: In this study, the use of an atypical antipsychotic was associated with a modest but statistically significant increase in the 30-day risk of a hospitalization with hyponatremia. The association was less pronounced than that described with other psychotropic drugs

Association of Sex With Stroke and Bleeding Risk of Apixaban and Rivaroxaban in Elderly Atrial Fibrillation Patients Using Propensity Score Weights

Background: Evidence from clinical trials suggests a differential effect of sex on the effectiveness and safety of direct oral anticoagulants (DOACs) for stroke prophylaxis in atrial fibrillation (AF). Methods: This population-based cohort study examined the independent effect of sex on hemorrhage and ischemic stroke in 23,884 patients (55% females; age ≥ 66 years) with AF starting apixaban or rivaroxaban treatment in Ontario, Canada. Patients were followed for 90 days after their DOAC prescription. Using female sex as the exposure of interest, differences in baseline characteristics were balanced between sexes using inverse probability weights based on propensity scores. Applying weighted modified Poisson regression, risk ratios (RRs) were estimated for major hemorrhage, ischemic stroke/systemic embolism/transient ischemic attack (hereafter stroke), myocardial infarction, and all-cause mortality, with males as a reference. Results: Females were older, had higher predicted stroke risk (based on CHADS2 score), and had fewer comorbidities than did males. Males had a higher prevalence of coronary artery disease, diabetes, and cancer, and similar predicted bleeding risk (based on HAS-BLED score). After weighting, baseline characteristics were well balanced. The 90-day risks for hemorrhage (RR 0.96; 95% confidence interval [CI] 0.80-1.15; P = 0.69) and stroke (RR 1.01; 95% CI 0.86-1.19; P = 0.94) were similar between sexes, which remained true when assessing each DOAC separately by dosing regimen. Compared to males, females had a lower risk for myocardial infarction (RR 0.66; 95% CI 0.52-0.84; P = 0.0008), and for all-cause mortality (RR 0.76; 95% CI 0.67-0.87; P \u3c 0.0001). Conclusions: Our findings do not suggest an association of sex with the 90-day risk of hemorrhage or ischemic stroke in older AF patients prescribed apixaban or rivaroxaban