National comprehensive cancer network recommendations for drugs without US food and drug administration approval in metastatic breast cancer: A cross-sectional study.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines can include recommendations for off-label use of anti-cancer drugs. Here, we evaluate NCCN recommendations not supported by US Food and Drug Administration (FDA) approval and explore associations with such recommendations. METHODS: All NCCN recommendations for MBC and their supporting data were identified. Drug labels were reviewed to determine whether recommendations are FDA approved. Logistic regression was used to compare FDA approved and off-label recommendations for pre-specified categories, including drug type, tumor subtype, level of recommendation and line of therapy. RESULTS: Of 124 recommendations identified, 68 (55%) were off-label. Chemotherapy and human epidermal growth factor receptor 2 (HER2) targeted drugs were associated with lower odds of FDA approval (OR = 0.28, p = 0.001 and OR = 0.29, 95% p = 0.005, respectively). Recommendations for endocrine therapy (OR = 3.44, p = 0.009) and non-HER2 targeted treatment (OR = 10.0, p < 0.001) were more commonly FDA approved indications. Compared to combination therapies, monotherapies were more likely to be FDA approved (OR = 3.45, p = 0.001) as were category 1 (OR = 7.63, p = 0.001) and preferred NCCN recommendations (OR = 4.07, p < 0.001). Compared to off-label recommendations, NCCN recommendations of approved drugs were based on significantly higher sample size (mean 477 vs. 342 patients, p = 0.02) and were non-significantly associated with availability of randomized data (OR = 2.0, 95% CI 0.89-4.49, p = 0.09). CONCLUSION: More than half of all NCCN recommendations for MBC are off-label, mostly involving chemotherapy containing regimes for HER2 negative disease and combinations which include HER2-targeted drugs. Improved transparency of NCCN guidelines may result from reporting of the strength of the evidence supporting recommendations for MBC.

Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Iron supplementation is crucial for the treatment of anemia of chronic kidney disease (CKD). Although intravenous (IV) iron is preferred for patients with CKD receiving dialysis (CKD stage 5D), the method of iron replacement for patients with CKD stages 3 to 5 is controversial. STUDY DESIGN: Systematic review and meta-analysis. A search was performed until October 2015 of MEDLINE, Cochrane Library, conference proceedings in nephrology, and reference lists of included trials. SETTING & POPULATION: Patients with CKD stages 3 to 5 or 5D. SELECTION CRITERIA FOR STUDIES: All randomized controlled trials, regardless of publication status or language. INTERVENTION: IV versus oral iron supplementation. OUTCOMES: The primary outcome was defined as percentage of patients reaching an elevation in hemoglobin (Hb) concentration > 1g/dL. Secondary end points included percentage of patients who reached Hb levels > 11g/dL, absolute Hb concentration, change in Hb concentration, transferrin saturation, ferritin levels, erythropoiesis-stimulating agents and blood transfusion requirement, and quality of life. Safety analysis included all-cause mortality and serious and all adverse events. RESULTS: 24 trials were identified, 13 including 2,369 patients with CKD stages 3 to 5 and 11 including 818 patients with CKD stage 5D. Patients treated with IV iron were more likely to reach an Hb response > 1g/dL (risk ratios [RRs] of 1.61 [95% CI, 1.39-1.87] for CKD stages 3-5 and 2.14 [95% CI, 1.68-2.72] for CKD stage 5D). Safety analysis showed similar rates of mortality and serious and any adverse effects. IV iron replacement was associated with higher risk for hypotension (RR, 3.71; 95% CI, 1.74-7.94) and fewer gastrointestinal adverse events (RR, 0.43; 95% CI, 0.28-0.67). LIMITATIONS: Significant heterogeneity between trials; follow-up was usually limited to 3 months. CONCLUSIONS: Our results agree with current recommendations for IV iron replacement for patients with CKD stage 5D and support increased use of IV iron for patients with CKD stages 3 to 5.

Measurement of electrical resistance of dermal-visceral zones as a diagnostic tool for gynecologic disorders.

BACKGROUND: Non-invasive screening tests may allow early diagnosis and prompt treatment, thereby potentially reducing morbidity and mortality and reducing costs for the community. This may be especially important for gynecologic pathologies that are difficult to promptly diagnose, such as endometriosis or ovarian cancer. OBJECTIVES: To evaluate the reliability of measuring skin resistance using the Medex Test for screening and diagnosis of gynecologic pathologies in a blinded single-center study. METHODS: We enrolled 150 patients: 59 with a functional disorder and 91 with an organic disease. Measurements were carried out in all patients and the results were analyzed separately by a second physician who was blinded to the patients' diagnosis. RESULTS: A high correlation was found between the clinical diagnosis and the results of the measurement of electrical skin resistance, with a specificity of 76.3% (45/59) for functional disorders and a sensitivity of 85.7% (78/91) for organic disorders, positive predictive value of 84.8% (78/92) and negative predictive value 77.6% (45/58). The kappa value for the results was 0.622, representing a value much better than expected randomly. CONCLUSIONS: The Medex Test has a good specificity and a high sensitivity for the diagnosis of gynecologic disorders. Further prospective studies are needed to validate these preliminary findings.