Renal medication-related clinical decision support (CDS) alerts and overrides in the inpatient setting following implementation of a commercial electronic health record: implications for designing more effective alerts.

OBJECTIVE: To assess the appropriateness of medication-related clinical decision support (CDS) alerts associated with renal insufficiency and the potential/actual harm from overriding the alerts. MATERIALS AND METHODS: Override rate frequency was recorded for all inpatients who had a renal CDS alert trigger between 05/2017 and 04/2018. Two random samples of 300 for each of 2 types of medication-related CDS alerts associated with renal insufficiency-"dose change" and "avoid medication"-were evaluated by 2 independent reviewers using predetermined criteria for appropriateness of alert trigger, appropriateness of override, and patient harm. RESULTS: We identified 37 100 "dose change" and 5095 "avoid medication" alerts in the population evaluated, and 100% of each were overridden. Dose change triggers were classified as 12.5% appropriate and overrides of these alerts classified as 90.5% appropriate. Avoid medication triggers were classified as 29.6% appropriate and overrides 76.5% appropriate. We identified 5 adverse drug events, and, of these, 4 of the 5 were due to inappropriately overridden alerts. CONCLUSION: Alerts were nearly always presented inappropriately and were all overridden during the 1-year period studied. Alert fatigue resulting from receiving too many poor-quality alerts may result in failure to recognize errors that could lead to patient harm. Although medication-related CDS alerts associated with renal insufficiency had previously been found to be the most clinically beneficial alerts in a legacy system, in this system they were ineffective. These findings underscore the need for improvements in alert design, implementation, and monitoring of alert performance to make alerts more patient-specific and clinically appropriate.

Lab monitoring and acute care utilization during initiation of renin angiotensin aldosterone inhibitors or diuretics in chronic kidney disease.

Renin angiotensin aldosterone system inhibitors (RAASi) and diuretics are among the most frequently prescribed anti-hypertensives. Individuals with chronic kidney disease (CKD) are particularly at risk for electrolyte disturbances and kidney injury but the appropriate use of lab monitoring following RAASi or diuretic initiation is uncertain in CKD.We describe the frequency and time interval of lab monitoring during initiation of RAASi and diuretics in CKD and assess whether close lab monitoring associates with one-year risk of emergency department (ED) visit or hospitalization.We evaluated an observational cohort of 8,217 individuals with stage 3-5 non-dialysis CKD newly prescribed a RAASi (52.3%) or diuretic (47.7%) from thirty-six primary care offices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital between 2009 and 2011.Overall, 3306 (40.2%) individuals did not have pre-prescription labs done within 2 weeks, and 5957 (72.5%) did not have post-prescription labs done within 2 weeks which includes 524 (6.4%) individuals without post-prescription within 1 year. Close monitoring occurred in only 1547 (20.1%) and was more likely in individuals prescribed diuretics compared to RAASi (adjusted OR 1.39; 95%CI 1.20-1.62), with CKD stage 4,5 compared with stage 3 (adjusted OR 1.47; 95%CI 1.16-1.86) and with cardiovascular disease (adjusted OR 1.42; 95%CI 1.21-1.66). Close monitoring was not associated with decreased risk of ED visit or hospitalization.Close lab monitoring during initiation of RAASi or diuretics was more common in participants with cardiovascular disease and advanced CKD suggesting physicians selected high-risk individuals for close monitoring. As nearly 80% of individuals did not receive close lab monitoring there may be value in future research on electronic physician decision tools targeted at lab monitoring.

Demystifying the Benefits and Harms of Anticoagulation for Atrial Fibrillation in Chronic Kidney Disease.

Patients with CKD represent a vulnerable population where the risks of atrial fibrillation, ischemic stroke, and bleeding are all heightened. Although large randomized, controlled trials in the general population clearly demonstrate that the benefits of warfarin and direct-acting oral anticoagulants outweigh the risks of bleeding, no such studies have been conducted in patients when their creatinine clearance falls below 25-30 ml/min. Without randomized, controlled trial data, the role of anticoagulation in patients with CKD with atrial fibrillation remains unclear and our practice is informed by a growing body of imperfect literature such as observational and pharmacokinetic studies. This article aims to present a contemporary literature review of the benefits versus harms of anticoagulation in atrial fibrillation for patients with CKD stages 3, 4, 5, and 5 on dialysis. Although unanswered questions and areas of clinical equipoise remain, this piece serves to assist physicians in interpreting the complex body of literature and applying it to their clinical care.

Kidney Biomarkers and Decline in eGFR in Patients with Type 2 Diabetes.

BACKGROUND AND OBJECTIVES: Biomarkers may improve identification of individuals at risk of eGFR decline who may benefit from intervention or dialysis planning. However, available biomarkers remain incompletely validated for risk stratification and prediction modeling. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined serum cystatin C, urinary kidney injury molecule-1 (uKIM-1), and urinary neutrophil gelatinase-associated lipocalin (UNGAL) in 5367 individuals with type 2 diabetes mellitus and recent acute coronary syndromes enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) trial. Baseline concentrations and 6-month changes in biomarkers were also evaluated. Cox proportional regression was used to assess associations with a 50% decrease in eGFR, stage 5 CKD (eGFR<15 ml/min per 1.73 m2), or dialysis. RESULTS: eGFR decline occurred in 98 patients (1.8%) over a median of 1.5 years. All biomarkers individually were associated with higher risk of eGFR decline (P<0.001). However, when adjusting for baseline eGFR, proteinuria, and clinical factors, only baseline cystatin C (adjusted hazard ratio per 1 SD change, 1.66; 95% confidence interval, 1.41 to 1.96; P<0.001) and 6-month change in urinary neutrophil gelatinase-associated lipocalin (adjusted hazard ratio per 1 SD change, 1.07; 95% confidence interval, 1.02 to 1.12; P=0.004) independently associated with CKD progression. A base model for predicting kidney function decline with nine standard risk factors had strong discriminative ability (C-statistic 0.93). The addition of baseline cystatin C improved discrimination (C-statistic 0.94), but it failed to reclassify risk categories of individuals with and without eGFR decline. CONCLUSIONS: The addition of cystatin C or biomarkers of tubular injury did not meaningfully improve the prediction of eGFR decline beyond common clinical factors and routine laboratory data in a large cohort of patients with type 2 diabetes and recent acute coronary syndrome. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_01_16_CJASNPodcast_18_3_G.mp3.

Association of Changes in Creatinine and Potassium Levels After Initiation of Renin Angiotensin Aldosterone System Inhibitors With Emergency Department Visits, Hospitalizations, and Mortality in Individuals With Chronic Kidney Disease.

Importance: Renin angiotensin aldosterone system inhibitors (RAASIs) benefit individuals with chronic kidney disease (CKD). Elevations in serum creatinine and potassium levels are common reasons for discontinuation of this therapy, but their incidence and risks are not well characterized in community practice. Objective: To evaluate associations of increased creatinine levels, hyperkalemia, and therapy continuation with the risk of emergency department (ED) visits, hospitalizations, and mortality within 1 year after RAASI therapy initiation in individuals with CKD. Design, Setting, and Participants: This prospective cohort study included 4661 individuals with nondialysis CKD newly prescribed a RAASI or a diuretic who were treated at 36 outpatient primary care offices affiliated with Brigham & Women's Hospital and Massachusetts General Hospital, Boston, from January 1, 2009, through December 31, 2011. Individuals receiving a new prescription for a diuretic were used to provide context. All participants had a baseline measure of renal function and at least 1 follow-up measurement of creatinine and potassium levels within 90 days of the prescription. Data were analyzed from January 1, 2009, through December 31, 2012. Exposures: Changes in creatinine and potassium levels within 90 days after the prescription date and therapy discontinuation. Main Outcomes and Measures: Emergency department visits, hospitalizations, and mortality within 1 year. Results: A total of 4661 individuals were included in the analysis (2506 [53.8%] women; mean [SD] age, 71 [14]; 3931 [84.3%] white; and 4198 [90.1%] with CKD stage 3). Of these, 2354 individuals (50.5%) received RAASIs and 2307 (49.5%) received diuretics. Creatinine level increase of at least 30% after RAASI therapy initiation was found in 158 of 2354 individuals (6.7%); hyperkalemia of greater than 5.0 mEq/L, in 251 of 2354 (10.7%). Increases in creatinine level of at least 30% (unadjusted odds ratio [OR], 1.40; 95% CI, 0.89-2.21), hyperkalemia (unadjusted OR, 1.15; 95% CI, 0.64-2.06), and therapy discontinuation (unadjusted OR, 1.01; 95% CI, 0.71-1.46) were not associated with ED visits or hospitalizations, which was consistent with results from competing risk analyses. Initial increases in creatinine level of at least 30% were associated with mortality in the total cohort (adjusted OR [aOR], 2.17; 95% CI, 1.45-3.25). However, the effect was only independent for diuretics (aOR, 2.27; 95% CI, 1.41-3.66) and not for RAASIs (aOR, 1.82; 95% CI, 0.83-3.99). Conclusions and Relevance: Acute creatinine and potassium level disturbances after initiation of RAASI therapy in individuals with CKD appear to be sustained often often not sustained and not associated with ED visits or hospitalizations, despite therapy continuation. Findings from this study suggest that increases in creatinine level were independently associated with mortality among individuals prescribed diuretics but not RAASIs. Structured laboratory monitoring during RAASI therapy initiation may guide appropriate continuation of therapy in the outpatient setting.

Chronotype is associated with the timing of the circadian clock and sleep in toddlers.

Chronotype is a construct reflecting individual differences in diurnal preference. Although chronotype has been studied extensively in school-age children, adolescents and adults, data on young children are scarce. This study describes chronotype and its relationship to the timing of the circadian clock and sleep in 48 healthy children aged 30-36 months (33.4 ± 2.1 months; 24 males). Parents completed the Children's Chronotype Questionnaire (CCTQ) ~2 weeks before the start of the study. The CCTQ provides three measures of chronotype: midsleep time on free days, a multi-item morningness/eveningness score and a single item chronotype score. After 5 days of sleeping on their habitual schedule (assessed with actigraphy and sleep diaries), children participated in an in-home salivary dim light melatonin onset assessment. Average midsleep time on free days was 1:47 ± 0:35, and the average morningness/eveningness score was 26.8 ± 4.3. Most toddlers (58.4%) were rated as 'definitely a morning type' or 'rather morning than evening type', while none (0%) were rated as 'definitely evening type'. More morning types (midsleep time on free days and morningness/eveningness score, respectively) had earlier melatonin onset times (r = 0.45, r = 0.26), earlier habitual bedtimes (r = 0.78, r = 0.54), sleep onset times (r = 0.80, r = 0.52), sleep midpoint times (r = 0.90, r = 0.53) and wake times (r = 0.74, r = 0.34). Parent ratings using the single-item chronotype score were associated with melatonin onset (r = 0.32) and habitual bedtimes (r = 0.27), sleep onset times (r = 0.33) and sleep midpoint times (r = 0.27). Morningness may best characterize circadian preference in early childhood. Associations between chronotype and circadian physiology and sleep timing suggest adequate validity for the CCTQ in this age group. These findings have important implications for understanding the marked variability in sleep timing during the early years of life.