Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors: A Retrospective Cohort Study.

Cisplatin, a major antineoplastic drug used in the treatment of solid tumors, is a known nephrotoxin. This retrospective cohort study evaluated the prevalence and severity of cisplatin nephrotoxicity in 54 children and its impact on height and weight.We recorded the weight, height, serum creatinine, and electrolytes in each cisplatin cycle and after 12 months of treatment. Nephrotoxicity was graded as follows: normal renal function (Grade 0); asymptomatic electrolyte disorders, including an increase in serum creatinine, up to 1.5 times baseline value (Grade 1); need for electrolyte supplementation <3 months and/or increase in serum creatinine 1.5 to 1.9 times from baseline (Grade 2); increase in serum creatinine 2 to 2.9 times from baseline or need for electrolyte supplementation for more than 3 months after treatment completion (Grade 3); and increase in serum creatinine ≥3 times from baseline or renal replacement therapy (Grade 4).Nephrotoxicity was observed in 41 subjects (75.9%). Grade 1 nephrotoxicity was observed in 18 patients (33.3%), Grade 2 in 5 patients (9.2%), and Grade 3 in 18 patients (33.3%). None had Grade 4 nephrotoxicity. Nephrotoxicity patients were younger and received higher cisplatin dose, they also had impairment in longitudinal growth manifested as statistically significant worsening on the height Z Score at 12 months after treatment. We used a multiple logistic regression model using the delta of height Z Score (baseline-12 months) as dependent variable in order to adjust for the main confounder variables such as: germ cell tumor, cisplatin total dose, serum magnesium levels at 12 months, gender, and nephrotoxicity grade. Patients with nephrotoxicity Grade 1 where at higher risk of not growing (OR 5.1, 95% CI 1.07-24.3, P=0.04). The cisplatin total dose had a significant negative relationship with magnesium levels at 12 months (Spearman r=-0.527, P=<0.001).

Designed delays versus rigorous pragmatic trials: lower carat gold standards can produce relevant drug evaluations.

BACKGROUND: Centralized administrative databases enable low-cost pragmatic randomized trials (PRTs) of drug effectiveness and safety. We simplified the PRT strategy by using designed delays (DD) to evaluate drug policies. OBJECTIVES: To reassess our DD trial of a cost-saving nebulizer-to-inhaler conversion policy and a proposed DD trial of reduced restrictions on Cox-2 inhibitors. RESEARCH DESIGN: We randomized 52 pairs of communities and clusters of physician practices to the policy either on time or after a 6-month delay. Our 2-stage qualitative reassessment comprised: (1) applying criteria for reporting PRTs and (2) assessing DD trials in 3 domains of responsibility: policymakers' decisions, researchers' decisions, and joint decisions involving negotiation. MEASURES: A draft checklist of 22 Consolidated Standards of Reporting Trials (CONSORT). Researchers' recollections of their degree of influence on decisions. RESULTS: DD trials deviated from ideal PRTs in the policymakers' domain: the policies affected mixtures of drugs, users, and illnesses, and implementation was not by strict protocol. Aspects negotiated by researchers and policymakers also deviated from ideal: length of delay; size and location of control group; unit of randomization; additional data collection; and communications to physicians. The DD trials complied better with CONSORT in the researchers' domain of analysis and interpretation. CONCLUSIONS: DD trials can be negotiated with policymakers. Low cost and simplicity of DD trials partly compensate for some limitations for evaluating drug safety and effectiveness. The ethics question of whether a DD is routine evaluation or research depends on its purpose and generalizability.

Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia.

OBJECTIVE: Does the use of nifedipine and magnesium sulfate together increase serious magnesium-related effects? STUDY DESIGN: This was a retrospective chart review of women who were admitted to BC Women's Hospital and Health Centre (1997-2001) and were given intravenous magnesium sulfate for preeclampsia. Serious magnesium-related effects were compared among 162 cases who received magnesium sulfate and contemporaneous nifedipine and 215 control subjects who received magnesium sulfate and either another antihypertensive (n=32 women) or no antihypertensive (n=183 women) medication. Chi-squared test, Fisher's exact test, or the Student t test was used for data comparison between cases and each control group. A probability value of <.05 was considered statistically significant. RESULTS: The cases had more severe preeclampsia and a longer magnesium sulfate infusion. However, cases had no excess of neuromuscular weakness (53.1%) versus control subjects who received antihypertensive medication (53.1%; P=.99) or control subjects who received no antihypertensive medication (44.8%; P=.13) or other serious magnesium-related effects. Cases versus control subjects who received antihypertensive medication had less neuromuscular blockade (odds ratio, 0.04; 95% CI, 0.002-0.80). Cases versus control subjects who received no antihypertensive medication had less maternal hypotension (41.4% vs 53.0%; P=.04). CONCLUSION: The use of nifedipine and magnesium sulfate together does not increase the risk of serious magnesium-related effects.