Clinical Outcomes of Failing to Dose-Reduce Cephalosporin Antibiotics in Older Adults with CKD.

BACKGROUND AND OBJECTIVES: Current dosing recommendations for cephalosporin antibiotics are on the basis of pharmacokinetic studies and are frequently ignored in practice. This study was undertaken to investigate the clinical outcomes of failing to dose-reduce cephalosporin antibiotics in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Retrospective cohort study conducted in Ontario, Canada using linked population-based health care databases. Nine thousand three hundred forty-seven outpatients (median age 83; interquartile range, 77-88 years; 57% women) with an eGFR<30 ml/min per 1.73 m2 and no prior history of dialysis were dispensed oral cephalexin, cefuroxime, or cefprozil between April of 2007 and March of 2016. Two thirds of the patients (6253 of 9347) received a higher than recommended daily dose of cephalexin (>1000 mg), cefuroxime (>500 mg), or cefprozil (>500 mg). The primary outcome was a hospital encounter (emergency room visit or hospital admission) with a condition listed as a possible side-effect of cephalosporins. Secondary outcomes were antibiotic treatment failure and all-cause mortality. All measures were assessed in the 30 days after cephalosporin initiation. RESULTS: Patients who received a higher than recommended dose of a cephalosporin antibiotic were similar in multiple indicators of baseline health to patients who received a reduced dose. Overall, 6% of patients presented to hospital with a possible cephalosporin side-effect, 13% failed antibiotic treatment, and 3% died. Compared with a reduced dose, receiving a higher dose of antibiotic was not associated with a different rate of side-effects (adjusted odds ratio, 1.00; 95% confidence interval, 0.84 to 1.20), treatment failure (1.01; 0.88 to 1.15), or death (0.99; 0.76 to 1.29). CONCLUSIONS: In this study we failed to demonstrate any association between the dose of cephalosporin antibiotic administered to elderly patients with CKD and the risk of side-effects leading to hospitalization, treatment failure, or mortality.

Validation of Living Donor Nephrectomy Codes.

BACKGROUND: Use of administrative data for outcomes assessment in living kidney donors is increasing given the rarity of complications and challenges with loss to follow-up. OBJECTIVE: To assess the validity of living donor nephrectomy in health care administrative databases compared with the reference standard of manual chart review. DESIGN: Retrospective cohort study. SETTING: 5 major transplant centers in Ontario, Canada. PATIENTS: Living kidney donors between 2003 and 2010. MEASUREMENTS: Sensitivity and positive predictive value (PPV). METHODS: Using administrative databases, we conducted a retrospective study to determine the validity of diagnostic and procedural codes for living donor nephrectomies. The reference standard was living donor nephrectomies identified through the province's tissue and organ procurement agency, with verification by manual chart review. Operating characteristics (sensitivity and PPV) of various algorithms using diagnostic, procedural, and physician billing codes were calculated. RESULTS: During the study period, there were a total of 1199 living donor nephrectomies. Overall, the best algorithm for identifying living kidney donors was the presence of 1 diagnostic code for kidney donor (ICD-10 Z52.4) and 1 procedural code for kidney procurement/excision (1PC58, 1PC89, 1PC91). Compared with the reference standard, this algorithm had a sensitivity of 97% and a PPV of 90%. The diagnostic and procedural codes performed better than the physician billing codes (sensitivity 60%, PPV 78%). LIMITATIONS: The donor chart review and validation study was performed in Ontario and may not be generalizable to other regions. CONCLUSIONS: An algorithm consisting of 1 diagnostic and 1 procedural code can be reliably used to conduct health services research that requires the accurate determination of living kidney donors at the population level.

CONTEXTE: Les professionnels de la santé se fient de plus en plus aux données administratives pour évaluer l'issue de l'opération chez les donneurs de rein vivants, étant donné la rareté des complications et les défis posés par la perte des patients au cours du suivi. OBJECTIF: Nous souhaitions évaluer la validité des données de néphrectomies sur donneur vivant rapportées dans les bases de données administratives en santé comparativement à la norme de référence qui consiste à consigner les données manuellement dans les dossiers médicaux. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective. CADRE DE L'ÉTUDE: L'étude a été menée dans l'un des cinq principaux centres de transplantation d'Ontario, au Canada. PARTICIPANTS: La cohorte était composée de donneurs de rein vivants dont la néphrectomie a eu lieu entre 2003 et 2010. MESURES: Sensibilité et valeur prédictive positive (VPP). MÉTHODOLOGIE: Dans le cadre d'une étude rétrospective menée à l'aide de bases de données administratives, nous avons examiné la validité des codes de diagnostic et des codes d'intervention dans les cas de néphrectomie sur donneur vivant. Les données de l'organisme ontarien d'approvisionnement en organes, vérifiées manuellement par analyse des dossiers médicaux, ont servi de norme de référence. On a déterminé les paramètres fonctionnels (la sensibilité et la VPP) de plusieurs algorithmes basés sur les codes de diagnostic, les codes d'intervention et les codes de facturation. RÉSULTATS: Il y a eu 1 199 néphrectomies sur donneur vivant pendant la période couverte par l'étude. Globalement, le meilleur algorithme de repérage des donneurs de rein vivants combinait i) un code de diagnostic attribué à un donneur de rein (ICD-10 Z52.4) et ii) un code d'intervention attribué à l'ablation ou au prélèvement rénal (1PC58, 1PC89, 1PC91). En comparaison avec la norme de référence, cet algorithme présente une sensibilité de 97 % et une VPP de 90 %. Les codes de diagnostic et d'intervention se sont avérés de meilleurs indicateurs que les codes de facturation du médecin (sensibilité de 60 %; VPP de 78 %). LIMITES DE L'ÉTUDE: L'examen des dossiers médicaux des donneurs et l'étude de validation ayant été menés en Ontario, ses conclusions peuvent ne pas être transposables à d'autres régions. CONCLUSION: Un algorithme combinant un code de diagnostic et un code d'intervention s'est avéré fiable pour le dénombrement des donneurs de rein vivants dans la population générale en contexte de recherche en santé.

Gabapentin dose and the 30-day risk of altered mental status in older adults: A retrospective population-based study.

Gabapentin is an effective treatment for chronic neuropathic pain but may cause dizziness, drowsiness, and confusion in some older adults. The goal of this study was to assess the association between gabapentin dosing and adverse outcomes by obtaining estimates of the 30-day risk of hospitalization with altered mental status and mortality in older adults (mean age 76 years) in Ontario, Canada initiated on high dose (>600 mg/day; n = 34,159) compared to low dose (≤600 mg/day; n = 76,025) oral gabapentin in routine outpatient care. A population-based, retrospective cohort study assessing new gabapentin use between 2002 to 2014 was conducted. The primary outcome was 30-day hospitalization with an urgent head computed tomography (CT) scan in the absence of evidence of stroke (a proxy for altered mental status). The secondary outcome was 30-day all-cause mortality. The baseline characteristics measured in the two dose groups were similar. Initiation of a high versus low dose of gabapentin was associated with a higher risk of hospitalization with head CT scan (1.27% vs. 1.06%, absolute risk difference 0.21%, adjusted relative risk 1.29 [95% CI 1.14 to 1.46], number needed to treat 477) but not a statistically significant higher risk of mortality (1.25% vs. 1.16%, absolute risk difference of 0.09%, adjusted relative risk of 1.01 [95% CI 0.89 to 1.14]). Overall, the risk of being hospitalized with altered mental status after initiating gabapentin remains low, but may be reduced through the judicious use of gabapentin, use of the lowest dose to control pain, and vigilance for early signs of altered mental status.

Association Between Handgrip Muscle Strength and Cardiometabolic z-Score in Children 6 to 19 Years of Age: Results from the Canadian Health Measures Survey.

BACKGROUND: It is unclear if muscle strength, another index of fitness, which confers the protection from cardiometabolic risk in adults, is associated with similar protection in children and youth. The purpose of this study was to investigate the association between handgrip strength and cardiometabolic health in a large Canadian sample of children and youth. METHODS: We performed a cross-sectional analysis of the Canadian sample of children and youth aged 6 to 19 years (n = 1376) studied in the Canadian Health Measures Survey (cycles 1 and 2) between 2007 and 2011. The primary exposure variable, handgrip strength, was measured using a handgrip dynamometer. The primary outcome measure was a composite measure of cardiometabolic risk calculated as the sum of z-scores of the following variables: triglycerides, low high-density lipoprotein cholesterol, systolic and diastolic blood pressures, and hemoglobin A1c. All of the analyses were adjusted for confounders. RESULTS: The sample was on average 12.8 ± 3.5 years and displayed a body mass index (BMI) z-score of 0.5 ± 1.2. In unadjusted analyses, handgrip strength was negatively associated with cardiometabolic z-score (estimate = -0.013; P < 0.001). When results were adjusted for age, BMI z-score, and cardiorespiratory fitness, the association was no longer significant; however, an interaction between handgrip strength, sex, and cardiometabolic z-score was observed (estimate = -0.042; P < 0.001). When analyses were stratified by sex, handgrip strength was negatively associated with cardiometabolic z-score (estimate = -0.038; P < 0.001) in girls, but not in boys (estimate = 0.008; P = 0.150). CONCLUSION: In a large sample of Canadian children and adolescents, handgrip strength was associated with cardiometabolic health in girls, but not in boys.