Carboplatin Dosing in Children Using Estimated Glomerular Filtration Rate: Equation Matters.

Renal function-based carboplatin dosing using measured glomerular filtration rate (GFR) results in more consistent drug exposure than anthropometric dosing. We aimed to validate the Newell dosing equation using estimated GFR (eGFR) and study which equation most accurately predicts carboplatin clearance in children with retinoblastoma. In 13 children with retinoblastoma 38 carboplatin clearance values were obtained from individual fits using MWPharm++. Carboplatin exposure (AUC) was calculated from administered dose and observed carboplatin clearance and compared to predicted AUC calculated with a carboplatin dosing equation (Newell) using different GFR estimates. Different dosing regimens were compared in terms of accuracy, bias and precision. All patients had normal eGFR. Carboplatin exposure using cystatin C-based eGFR equations tended to be more accurate compared to creatinine-based eGFR (30% accuracy 76.3-89.5% versus 76.3-78.9%, respectively), which led to significant overexposure, especially in younger (aged ≤ 2 years) children. Of all equations, the Schwartz cystatin C-based equation had the highest accuracy and lowest bias. Although anthropometric dosing performed comparably to many of the eGFR equations overall, we observed a weight-dependent change in bias leading to underdosing in the smallest patients. Using cystatin C-based eGFR equations for carboplatin dosing in children leads to more accurate carboplatin-exposure in patients with normal renal function compared to anthropometric dosing. In children with impaired kidney function, this trend might be more pronounced. Anthropometric dosing is hampered by a weight-dependent bias.

Why pediatricians fail to diagnose hypertension: a multicenter survey.

OBJECTIVE: To elucidate why pediatricians fail to diagnose childhood hypertension, with special emphasis on the use of blood pressure (BP) reference data. We hypothesized that pediatricians frequently omit BP measurements and do not routinely relate BP measurements to reference data. STUDY DESIGN: We conducted a multicenter survey on BP measurement among 197 participants. Respondents were asked to estimate BP percentiles and classify BP readings in 12 example cases. Questionnaires were completed onsite in the presence of the researchers, without access to BP reference data. RESULTS: We found that 71% of physicians measure BP during ambulatory visits only if the child has risk factors for hypertension. After measuring BP, 65% compare the reading with reference data only if they suspect that it is elevated. Their ability to rate a reading at its true value is limited, however; 47% of the physicians classified 1 or more of the prehypertensive or hypertensive cases as normal. CONCLUSIONS: Most pediatricians do not screen for hypertension, contrary to recommendations. After obtaining a BP measurement, the majority do not compare the reading with reference standards; however, without the use of reference data, they commonly underestimate the BP percentile and potentially miss cases of childhood hypertension.

Diversity in renal function monitoring and dose modifications during treatment for childhood cancer: a call for standardization.

Despite changes in survival and drug tolerability, nephrotoxicity remains an important complication of chemotherapy. To provide cutting-edge care for children with cancer oncologist must be familiar with their nephrotoxic potential. Careful monitoring of renal function during treatment is therefore indicated. Well-defined guidelines for this are lacking. We reviewed current DCOG protocols and showed that monitoring of renal function during treatment varies widely between protocols. In some protocols recommended renal function measures are inappropriate given the chemotherapy prescribed. Advices on dose modifications in case of renal dysfunction also vary, even with comparable regimens. These differences are unwanted and call for standardization.

Height-independent estimation of glomerular filtration rate in children: an alternative to the Schwartz equation.

OBJECTIVE: To compare the diagnostic performance of 2 height-independent equations used to calculate estimated glomerular filtration rate (eGFR), those of Pottel (eGFR-Pottel) and the British Columbia Children's Hospital (BCCH) (eGFR-BCCH), with the commonly used Schwartz equation (eGFR-Schwartz). STUDY DESIGN: We externally validated eGFR-Pottel and eGFR-BCCH in a well-characterized pediatric patient population (n = 152) and compared their diagnostic performance with that of eGFR-Schwartz using Bland-Altman analysis. All patients underwent glomerular filtration rate measurement using the gold standard single-injection inulin clearance method (GFR-inulin). RESULTS: Median GFR-inulin was 92.0 mL/min/1.73 m² (IQR, 76.1-107.4 mL/min/1.73 m²). Compared with GFR-inulin, the mean bias for eGFR-Schwartz was -10.1 mL/min/1.73 m(2) (95% limits of agreement [LOA], -77.5 to 57.2 mL/min/1.73 m(2)), compared with -12.3 mL/min/1.73 m² (95% LOA, -72.6 to 47.9 mL/min/1.73 m(2)) for eGFR-Pottel and -22.1 mL/min/1.73 m² (95% LOA, -105.0 to 60.8 mL/min/1.73 m(2)) for eGFR-BCCH. eGFR-Pottel showed comparable accuracy to eGFR-Schwartz, with 77% and 76% of estimates within 30% of GFR-inulin, respectively. eGFR-BCCH was less accurate than eGFR-Schwartz (66% of estimates within 30% of GFR-inulin; P < .01). CONCLUSION: The performance of eGFR-Pottel is superior to that of eGFR-BCCH and comparable with that of eGFR-Schwartz. eGFR-Pottel is a valid alternative to eGFR-Schwartz in children and could be reported by the laboratory if height data are not available.

MR-guided breast biopsy at 3T: diagnostic yield of large core needle biopsy compared with vacuum-assisted biopsy.

OBJECTIVE: The purpose of this study was to evaluate two MR-guided biopsy techniques at 3 T, large core needle breast biopsy (LCNB) and vacuum-assisted breast biopsy (VAB) and to compare the diagnostic yield and rate of complications to determine the optimal biopsy technique at 3 T. METHODS: 55 LCNB and 64 VAB were consecutively performed. Benign biopsy results were verified by retrospective correlation of histology, with pre-interventional, post-interventional MRI studies and follow-up and were classified as representative or non-representative. Time to follow-up was up to 2 years for the considered non-representative benign lesions. Statistical analysis was performed using the Chi-squared test. RESULTS: LCNB was technically successful in 100% of patients (55/55) and VAB in 98% of patients (63/64). Histopathological analysis resulted in 45 (82%) benign, 3 (5%) high-risk and 7 (13%) malignant lesions for LCNB and 43 (67%) benign, 3 (5%) high-risk and 18 (28%) malignant lesions. Distribution was significantly different (p < 0.001), favouring VAB over LCNB. CONCLUSION: Because of the substantially higher diagnostic yield and certainty of a benign diagnosis, VAB is the optimal biopsy technique at 3 T. LCNB should be considered when VAB is not feasible.

Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy.

BACKGROUND: Monitoring of renal function is crucial in pediatric oncology. The use of creatinine to estimate glomerular filtration rate (GFR) is hampered by its dependency on muscle mass. Muscle wasting is common in children with cancer, leading to overestimation of GFR. Data on cystatin C are sparse in pediatric oncology, although this marker could be particularly useful in this population. PROCEDURE: Inulin clearance, estimated GFR using serum cystatin C according to Filler (eGFRcys) and serum creatinine according to Schwartz (eGFRcrea) were measured in 68 children with malignancy and 121 controls. We analyzed the difference between measured and estimated GFR and performance, bias and accuracy. RESULTS: Multiple linear regression analysis showed overestimation of GFR by eGFRcrea in females (B = -21.18; P = 0.001), and in patients with malignancy (B = -21.77; P = 0.014). eGFRcys overestimated GFR in females (B = -10.47; P = 0.001), but was independent of treatment for malignancy. Agreement with gold standard in detecting GFR below 90 ml/min/1.73 m(2) is better for eGFRcys (AUC 0.854) than for eGFRcrea (AUC 0.675) in the group with cancer. They performed comparably in the control group. Bland-Altman analysis showed considerable bias for eGFRcrea compared to eGFRcys (-14.3 ml/min/1.73 m(2) vs. -7.3 ml/min/1.73 m(2)). The proportion of estimates within 30% of true GFR for eGFRcrea (72.1%) was lower than for eGFRcys (82.4%) in the group with cancer. In the control group eGFRcrea (84.3%) outperformed eGFRcys (76.0%). When using the 50% limits of agreement, eGFRcys outperformed eGFRcrea in both groups. CONCLUSION: Cystatin C more accurately detects mildly impaired renal function than creatinine in children receiving treatment for malignancy.

Anticancer conjugates and cocktails based on methotrexate and nucleoside synergism.

Conjugates of methotrexate (MTX) and the nucleoside analogs 3-azidodeoxythymidine (AZT), iododeoxyuridine (IUdR) and dideoxycytidine (ddC) linked using poly(ethyleneglycol) are presented. In vitro cytotoxicity assays of the conjugates against drug resistant ovarian cell line A2780/AD are preformed and comparisons made to such assays performed for unconjugated (cocktail) systems. All systems tested were inactive, or had low activity, at 24 h. After 72 hr incubation however, the cocktails of MTX and AZT, IUdR or ddC showed high cytotoxicity in the low nanomolar range. The conjugates were only very moderately active with IC(50) values in the [0.1 to 1.0 mM] range. Conjugation of the antifolate to the nucleoside analogs has it seems reduced the activity significantly when compared to a cocktail of the components, indicating a conjugate approach is unlikely to translate into success in vivo. The positive note comes from the observation that by combining two of the new conjugates, namely those based on MTX with IUdR or AZT, an IC50 at 24 hours of ~ [180 muM] was produced.

Quality of care and use of the medical home in a state-funded capitated primary care plan for low-income children.

OBJECTIVE: To evaluate the quality of care and use of the medical home in a state-funded capitated insurance plan for low-income children-the Colorado Child Health Plan (CCHP). DESIGN: A retrospective cohort study using medical record review at pediatric and family practice offices in 4 geographic areas of Colorado. At each practice, CCHP-enrolled children (6 months to 6.5 years) and 2 controls were selected, 1 with Medicaid (MK) and 1 with private insurance (PI), matched by date of birth to the CCHP-enrolled child (N = 596). CCHP-enrolled children with a diagnosis of asthma, aged 3 to 18 years, and asthmatic children with MK and PI, matched by age, were also selected from each practice (N = 139). RESULTS: Quality of preventive services were comparable in the 3 groups. CCHP-enrolled children made more health maintenance visits than MK-enrolled children (1.3 CCHP vs.9 MK vs 1.1 PI) and were more frequently screened for lead (8.1% CCHP vs 3.4% MK vs 1.2% PI) and anemia (5.0% CCHP vs 4.4% MK vs 2.4% PI) than children in either control group. Documented immunization rates were similar in the 3 groups, but a shift in location of immunization from public health clinics to the primary care site was seen in the CCHP group. CCHP-enrolled children made more office visits for acute care than did MK-enrolled children (4.1 CCHP vs 3.1 MK vs 3.4 PI), but a higher proportion of these visits took place at the medical home rather than the emergency department for the CCHP group (.04) as compared with the MK (.07) or PI (.06) groups. Asthmatic children in the CCHP group made more preventive office visits for maintenance therapy and more frequently used the primary care site rather than the emergency department for acute exacerbations than did children with PI (mean ratio of emergency department visits to total acute visits.04 CCHP vs.06 MK vs.19 PI). CONCLUSIONS: Despite capitated reimbursement for primary care services, CCHP provided children from low-income families with preventive, acute, and chronic care services of comparable quantity and quality to those received by children with MK or PI. The program was associated with a shift of immunization location to the primary care site and increased health maintenance care for new enrollees. CCHP-enrolled children used their medical home for the majority of acute health needs and were not high utilizers of emergency department or hospital services.

Symptom management outcomes. Do they reflect variations in care delivery systems?

OBJECTIVES: Symptom management is increasingly recognized as a critical element of patient care, particularly in managing chronic illness. However, research on outcomes related to symptom management is in its infancy, except for the symptom of pain. This symptom was therefore chosen as a prototype to review the state of the science regarding relations between organizational variables and symptom management outcomes and to illustrate the issues regardless of the symptom managed. This article discusses pain outcome measures appropriate for acute and cancer pain, proposes attributes of the care delivery system that may affect outcome measures, and identifies challenges associated with this type of research. METHODS: Review of quality assurance studies raises issues concerning the adequacy of currently used outcomes for pain and satisfaction with pain management. Although considerable effort has been expended in developing pain measurement in adults and children, critical issues for examining pain management outcomes include deciding what perspectives should be used as the most valid indicator of the pain outcome and when the measures should be obtained. RESULTS: Critical concerns are raised about the measure of satisfaction with pain management and its appropriateness as the end-result outcome. A key issue is whether respondents actually disentangle satisfaction with pain management from satisfaction with other aspects of care, including caring dispositions of health-care providers. Finally, the question is raised: Are pain outcomes affected by organizational context? CONCLUSIONS: Although the answer to this question is unknown, a few research studies suggest that organizational context is likely to influence pain outcomes. It is clear, however, from ongoing work that until several conceptual, methodological, and analytic challenges are resolved, research is unlikely to capture the influence of variations in care delivery systems on symptom management outcomes.

Multisite clinical research: a challenge for nursing leaders.

The need for the application of research-based data to diversified healthcare systems has led to more attempts by nurse researchers to investigate phenomena across clinical sites. Nurse executives increasingly are asked to justify resource allocation among organizations, and must compare patient-care practices within complex systems that are often geographically distant. This article describes the pitfalls encountered and the progress made by researchers during a 4-year multisite, multimethod clinical investigation collecting clinical outcome and organizational context data from seven hospitals.

Evaluating a pediatric pain management research utilization program.

Research-based pain assessment and management innovations are not fully utilized in clinical nursing practice. Thus children continue to suffer despite strategies that could eliminate or significantly reduce their pain. An educational program was developed and implemented to integrate state-of-the-art pain assessment and management strategies into the clinical practice of pediatric nurses. This article reports on evaluation of the research utilization process during development and implementation of the program. The program included formal classes, development of instruments for pain assessment and documentation, ongoing consultation on pain management strategies, and designation of a unit-based staff nurse liaison. Findings illuminated the process through which nursing staff on one unit came to learn about new ideas, try those ideas in their clinical practice, re-invent certain strategies to better meet their needs, and, ultimately, to adopt innovations deemed helpful in their work.

Cancer pain guidelines: now that we have them, what do we do?

Addressing the what, who, when, where, and how of implementing the AHCPR guidelines is an attempt to simplify what may be an overwhelming process. Use the suggestions presented in Figure 1 to formulate an action plan, and remember to assign a time frame and individual accountability. The commitment to moving the guidelines from the bookshelf to the bedside begins now. Using a process such as this will assist efforts to improve care of patients in pain. It is our hope that a year from now the copy of the AHCPR cancer pain guidelines on your shelf will not be covered with dust but rather will be a well-worn text translated to practice.