RESUMO
BACKGROUND AND OBJECTIVE: Monitoring renal function is critical in treating pediatric patients, especially when dosing nephrotoxic agents. We evaluated the validity of the bedside Schwartz and Brandt equations in pediatric oncology patients and developed new equations for estimated glomerular filtration rate (eGFR) in these patients. METHODS: A retrospective analysis was conducted comparing eGFR using the bedside Schwartz and Brandt equations to measured GFR (mGFR) from technetium-99m diethylenetriamine pentaacetic acid (99mTc-DTPA) between January 2007 and August 2013. An improved equation to estimate GFR was developed, simplified, and externally validated in a cohort of patients studied from September 2013 to June 2015. Carboplatin doses calculated from 99mTc-DTPA were compared with doses calculated by GFR-estimating equations. RESULTS: Overall, the bedside Schwartz and Brandt equations did not precisely or accurately predict measured GFR (mGFR). Using a data subset, we developed a five-covariate equation, which included height, serum creatinine, age, blood urea nitrogen (BUN), and gender, and a simplified version (two-covariates), which contained height and serum creatinine. These equations were used to estimate GFR in 2036 studies, resulting in precise and accurate predictors of mGFR values. Equations were validated in an external cohort of 570 studies; both new equations were more accurate in calculating carboplatin doses than either the bedside Schwartz or Brandt equation. CONCLUSIONS: Two new equations were developed to estimate GFR in pediatric oncology patients, both of which did a better job at estimating mGFR than published equations.
Assuntos
Antineoplásicos/administração & dosagem , Carboplatina/administração & dosagem , Testes de Função Renal/métodos , Modelos Biológicos , Neoplasias/tratamento farmacológico , Adolescente , Antineoplásicos/farmacocinética , Carboplatina/farmacocinética , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Rim/metabolismo , Rim/fisiopatologia , Masculino , Neoplasias/fisiopatologia , Compostos Radiofarmacêuticos/administração & dosagem , Eliminação Renal , Insuficiência Renal Crônica , Estudos Retrospectivos , Pentetato de Tecnécio Tc 99m/administração & dosagemRESUMO
OBJECTIVE: To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. DATA SOURCES: A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for unpublished data, including data from the Infectious Diseases Society of America, the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society, and the Interscience Conference on Antimicrobial Agents and Chemotherapy, was conducted using similar search terms. STUDY SELECTION AND DATA EXTRACTION: In vitro and in vivo Phase 2, Phase 3, and postmarketing studies available in English, evaluating antiretroviral regimens that contain raltegravir for the treatment of HIV-1 infection in both ARV-naïve and ARV-experienced patients, were evaluated. Studies assessing raltegravir pharmacokinetics and pharmacodynamics were included for review. DATA SYNTHESIS: The nucleoside-based regimen of raltegravir with tenofovir/emtricitabine provides an effective first-line treatment option. However, nucleoside-sparing regimens appear unfavorable in ARV-naïve subjects and should be reserved for patients with limited treatment options. Raltegravir used with optimized background therapy provides an alternative regimen for ARV-experienced patients. This review describes the available in vitro and in vivo data on raltegravir potency, defined as the ability to achieve undetectable viral load, and safety profile, as well as comparison to standard HIV-1 therapies. CONCLUSIONS: Raltegravir has demonstrated potent antiretroviral activity against HIV-1 in both ARV-naïve and ARV-experienced subjects, with the benefits of a favorable adverse effect profile and minimal drug interactions. Raltegravir must be dosed twice daily, as once daily raltegravir displays decreased virologic efficacy compared to twice daily dosing. However, the ongoing development of new integrase strand transfer inhibitors may provide potent once daily regimens.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/uso terapêutico , Pirrolidinonas/uso terapêutico , Adenina/administração & dosagem , Adenina/análogos & derivados , Adenina/uso terapêutico , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Quimioterapia Combinada , Emtricitabina , Infecções por HIV/virologia , Inibidores de Integrase de HIV/efeitos adversos , Inibidores de Integrase de HIV/farmacocinética , HIV-1/isolamento & purificação , Humanos , Organofosfonatos/administração & dosagem , Organofosfonatos/uso terapêutico , Pirrolidinonas/efeitos adversos , Pirrolidinonas/farmacocinética , Raltegravir Potássico , TenofovirRESUMO
PURPOSE: This evidence-based guideline intends to support patients, clinicians, and others regarding interventions and processes to support patient adherence to oral anticancer medications (OAMs). METHODOLOGIC APPROACH: A panel of healthcare professionals and patient representatives developed a clinical practice guideline to support patients taking OAMs. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology and criteria for trustworthy guidelines were followed. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. A quantitative or narrative synthesis of the evidence was completed. Certainty of the evidence was assessed using GRADE. FINDINGS: The panel agreed on recommendations and suggested an adherence risk assessment, education addressing adherence, ongoing assessment, proactive follow-up, coaching, and motivational interviewing in addition to usual care. The panel suggested the implementation of a structured OAM program. IMPLICATIONS FOR NURSING: As cancer treatment shifts from clinic to home settings, interventions and programs to support patients on OAMs are needed.