Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study.

BACKGROUND: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes. METHODS: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines. RESULTS: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]). CONCLUSIONS: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Epidemiologic Characteristics of Acute Kidney Injury During Cisplatin Infusions in Children Treated for Cancer.

Importance: Few multicenter pediatric studies have comprehensively described the epidemiologic characteristics of cisplatin-associated acute kidney injury using standardized definitions. Objective: To examine the rate of and risk factors associated with acute kidney injury among children receiving cisplatin infusions. Design, Setting, and Participants: This prospective cohort study examined children (aged <18 years) recruited from May 23, 2013, to March 31, 2017, at 12 Canadian pediatric academic health centers who were receiving 1 or more cisplatin infusion. Children whose estimated or measured glomerular filtration rate (GFR) was less than 30 mL/min/1.73 m2 or who had received a kidney transplant were excluded. Data analysis was performed from January 3, 2018, to September 20, 2019. Exposures: Cisplatin infusions. Main Outcomes and Measures: The primary outcome was acute kidney injury during cisplatin infusion, defined using a Kidney Disease: Improving Global Outcomes serum creatinine criteria-based definition (stage 1 or higher). The secondary outcome was acute kidney injury defined by electrolyte criteria from the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1 or higher). Assessments occurred at early (first or second cycle) and late (last or second to last cycle) cisplatin infusions. Results: A total of 159 children (mean [SD] age at early cisplatin infusion, 7.2 [5.3] years; 80 [50%] male) participated. The most common diagnoses were central nervous system tumors (58 [36%]), neuroblastoma (43 [27%]), and osteosarcoma (33 [21%]). Acute kidney injury (by serum creatinine level increase) occurred in 48 of 159 patients (30%) at early cisplatin infusions and 23 of 143 patients (16%) at late cisplatin infusions. Acute kidney injury (by electrolyte abnormalities) occurred in 106 of 159 patients (67%) at early cisplatin infusion and 100 of 143 patients (70%) at late cisplatin infusions. Neuroblastoma diagnosis and higher precisplatin GFR were independently associated with acute kidney injury (serum creatinine level increase) at early cisplatin infusions (adjusted odds ratio [aOR] for neuroblastoma vs other, 3.25; 95% CI, 1.18-8.95; aOR for GFR, 1.01; 95% CI, 1.00-1.03) and late cisplatin infusions (aOR for neuroblastoma vs other, 6.85; 95% CI, 1.23-38.0; aOR for GFR, 1.01; 95% CI, 1.00-1.03). Higher cisplatin infusion dose was also independently associated with acute kidney injury (serum creatinine level increase) at later cisplatin infusions (aOR, 1.05; 95% CI, 1.01-1.10). Conclusions and Relevance: The findings suggest that acute kidney injury is common among children receiving cisplatin infusions and that rate and risk factors differ at earlier vs later infusions. These results may help with risk stratification with a goal of risk reduction.

Patient-Reported Discharge Readiness and 30-Day Risk of Readmission or Death: A Prospective Cohort Study.

BACKGROUND: Early readmissions to hospital after discharge are common, and clinicians cannot accurately predict their occurrence. We examined whether patients who feel unready at the time of discharge have increased readmissions or death within 30 days. METHODS: This was a prospective cohort study of adult patients discharged home from 2 tertiary care hospitals in Edmonton, Alberta, Canada, between October 2013 and November 2014. Patient-reported discharge readiness was measured with an 11-point Likert response scale, with scores <7 indicating subjective unreadiness. The primary outcome was readmission or death within 30 days. Logistic regression models were adjusted for age, sex, and a validated risk prediction score for postdischarge events (LACE index). RESULTS: Of 495 patients (mean age 62 years, 51% female, mean Charlson comorbidity index 2.8), 112 (23%) reported being unready for discharge. Risk factors for being unready at discharge were cognitive impairment (mild vs none), low satisfaction with health care services, depression, lower education, previous hospital admissions (12 months), and persistent symptoms or disability. At 30 days, 85 patients (17%) had been readmitted or died, with no significant difference between patients who felt unready or ready (15% vs 18%, adjusted odds ratio 0.84, 95% confidence interval 0.46-1.54, P = .59). CONCLUSIONS: Although nearly one-quarter of hospitalized medical patients reported being unready at the time of discharge, they did not experience any higher risk of readmission or death in the first 30 days after discharge, compared with patients who felt ready for discharge.

Association between frailty and 30-day outcomes after discharge from hospital.

BACKGROUND: Readmissions after hospital discharge are common and costly, but prediction models are poor at identifying patients at high risk of readmission. We evaluated the impact of frailty on readmission or death within 30 days after discharge from general internal medicine wards. METHODS: We prospectively enrolled patients discharged from 7 medical wards at 2 teaching hospitals in Edmonton. Frailty was defined by means of the previously validated Clinical Frailty Scale. The primary outcome was the composite of readmission or death within 30 days after discharge. RESULTS: Of the 495 patients included in the study, 162 (33%) met the definition of frailty: 91 (18%) had mild, 60 (12%) had moderate, and 11 (2%) had severe frailty. Frail patients were older, had more comorbidities, lower quality of life, and higher LACE scores at discharge than those who were not frail. The composite of 30-day readmission or death was higher among frail than among nonfrail patients (39 [24.1%] v. 46 [13.8%]). Although frailty added additional prognostic information to predictive models that included age, sex and LACE score, only moderate to severe frailty (31.0% event rate) was an independent risk factor for readmission or death (adjusted odds ratio 2.19, 95% confidence interval 1.12-4.24). INTERPRETATION: Frailty was common and associated with a substantially increased risk of early readmission or death after discharge from medical wards. The Clinical Frailty Scale could be useful in identifying high-risk patients being discharged from general internal medicine wards.

Procedural sedation and analgesia in a Canadian ED: a time-in-motion study.

INTRODUCTION: Some patients presenting to emergency departments (EDs) suffer from conditions requiring potentially painful treatment; procedural sedation and analgesia (PSA) are important components of their management. The purpose of this study was to determine the resources used during the administration of PSA. METHODS: This prospective observational study was conducted in a Canadian urban teaching center. Detailed data concerning the dosage of PSA medications, adverse events, and ED times for patients requiring PSA for treatment of fractures, reductions of joint dislocations, and cardioversion for atrial fibrillation were collected. Descriptive analyses included proportions, means with standard deviations, and medians with interquartile ranges. RESULTS: Of the 177 PSA cases considered for analysis, 69.5% were orthopedic manipulations and 30.5% were cardioversions. Propofol alone or combined with fentanyl was the commonest medication, and 27 minor adverse events were documented. The median number of staff used in each PSA was 4 (4, 4). The median time from triage to the start of the procedure was 175 minutes (98, 259). The median time from the end of monitoring to discharge was 186 minutes (104, 316). The median time from the start of PSA administration to the end of patient monitoring was 12 minutes for fractures/dislocations and 7 minutes for cardioversion. The total ED length of stay was 6.6 hours. CONCLUSION: Procedural sedation and analgesia are potentially time-consuming interventions requiring the coordination of ED staff; delays in procedures represent opportunities to reduce ED overcrowding. Procedural sedation and analgesia guidelines may assist with standardization.