Palbociclib in hormone-receptor–positive advanced breast cancer

BackgroundGrowth of hormone-receptor–positive breast cancer is dependent on cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), which promote progression from the G1 phase to the S phase of the cell cycle. We assessed the efficacy of palbociclib (an inhibitor of CDK4 and CDK6) and fulvestrant in advanced breast cancer.MethodsThis phase 3 study involved 521 patients with advanced hormone-receptor–positive, human epidermal growth factor receptor 2–negative breast cancer that had relapsed or progressed during prior endocrine therapy. We randomly assigned patients in a 2:1 ratio to receive palbociclib and fulvestrant or placebo and fulvestrant. Premenopausal or perimenopausal women also received goserelin. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, objective response, rate of clinical benefit, patient-reported outcomes, and safety. A preplanned interim analysis was performed by an independent data and safety monitoring committee after 195 events of disease progression or death had occurred.ResultsThe median progression-free survival was 9.2 months (95% confidence interval [CI], 7.5 to not estimable) with palbociclib–fulvestrant and 3.8 months (95% CI, 3.5 to 5.5) with placebo–fulvestrant (hazard ratio for disease progression or death, 0.42; 95% CI, 0.32 to 0.56; P<0.001). The most common grade 3 or 4 adverse events in the palbociclib–fulvestrant group were neutropenia (62.0%, vs. 0.6% in the placebo–fulvestrant group), leukopenia (25.2% vs. 0.6%), anemia (2.6% vs. 1.7%), thrombocytopenia (2.3% vs. 0%), and fatigue (2.0% vs. 1.2%). Febrile neutropenia was reported in 0.6% of palbociclib-treated patients and 0.6% of placebo-treated patients. The rate of discontinuation due to adverse events was 2.6% with palbociclib and 1.7% with placebo.ConclusionsAmong patients with hormone-receptor–positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone. (Funded by Pfizer; PALOMA3 ClinicalTrials.gov number, NCT01942135.)

The catheter to vein ratio and rates of symptomatic venous thromboembolism in patients with a peripherally inserted central catheter (PICC): a prospective cohort study.

BACKGROUND: Peripherally inserted central catheters (PICCs) are a common vascular access device used in clinical practice. Their use may be complicated by adverse events such as venous thromboembolism (VTE). The size of the vein used for PICC insertion and thus the catheter to vein ratio is thought to be a controllable factor in the reduction of VTE rates in patients who have a PICC. However, an optimal catheter to vein ratio for PICC insertion has not previously been investigated to inform clinical practice. OBJECTIVES: To determine the effect of the catheter to vein ratio (proportion of the vein measured at the insertion point taken up by the catheter) on rates of symptomatic VTE in patients with a PICC and identify the optimal ratio cut-off point to reduce rates of this adverse event. METHOD: Adult patients waiting for PICC insertion at a large metropolitan teaching hospital were recruited between May and December 2013. Vein diameter at the PICC insertion site was measured using ultrasound with in-built callipers. Participants were followed up at eight weeks to determine if they developed symptomatic VTE. RESULTS: Data were available for 136 patients (50% cancer; 44% infection; 6% other indication for PICC). Mean age was 57 years with 54% males. There were four cases of confirmed symptomatic VTE (two involving the deep veins, one peripheral vein and one pulmonary embolism). Receiver operator characteristic (ROC) analysis determined that a 45% catheter to vein ratio was the ideal cut off point to maximise sensitivity and specificity (AUC 0.761; 95% CI 0.681-0.830). When a ratio of 46% or above was compared to one that was less than or equal to 45% using a log binomial generalised linear model it was found that participants with a catheter to vein ratio >45% were 13 times more likely to suffer VTE (relative risk 13, p=0.022; CI 1.445-122.788). CONCLUSION: It was found that a 45% catheter to vein ratio was the optimal cut off with high sensitivity and specificity to reduce the risk of VTE. However, further research is needed to confirm these results as although adequately powered; the number of cases of VTE was comparatively small, resulting in wide confidence intervals.

Vein measurement by peripherally inserted central catheter nurses using ultrasound: A reliability study

Background Peripherally inserted central catheters (PICCs) are increasingly inserted by trained registered nurses, necessitating the development of specialized skills such as the use of ultrasound. The selection of an adequately sized vein is an important factor in reducing adverse events such as deep vein thrombosis. However, PICC nurses may receive minimal training in the use of ultrasound for vein measurement. Objective We aimed to demonstrate the reliability of a vein measurement protocol using ultrasound by a PICC nurse trained in sonography. Methods The diameter of the basilic, brachial, and cephalic veins in the left arms of healthy participants (n = 12) were measured using ultrasound by a PICC nurse and a sonographer. A PICC nurse performed the measurement twice and the sonographer once; the PICC nurse's results were compared for intra-rater reliability and compared with the sonographer for inter-rater reliability. The results were analyzed using intraclass correlation coefficients (ICCs). Results Inter-rater reliability between the PICC nurse and the sonographer was adequate, the ICC for the brachial vein was 0.60 (95% confidence interval [CI], 0.06-0.87), basilic vein ICC was 0.87 (95% CI, 0.58-0.96) and cephalic vein ICC was 0.77 (95% CI, 0.39-0.93). Intra-rater reliability of the PICC nurse was higher; the ICC for the brachial vein was 0.80 (95% CI, 0.44-0.94), basilic vein ICC was 0.92 (95% CI, 0.67-0.98), and cephalic vein ICC was 0.78 (95% CI, 0.40-0.93). Conclusions Using a suitable protocol, a PICC nurse was able to measure vein diameter reliably when compared with a sonographer and consistently replicate these results.

Patient-controlled intranasal fentanyl analgesia: a pilot study to assess practicality and tolerability during childbirth

Background: Intranasal administration of fentanyl is a non-invasive method of analgesic delivery which has been shown to be effective. This pilot study aimed to assess the practicality and tolerability of patient-controlled intranasal fentanyl for relieving pain during childbirth. Methods: This prospective, non-randomised, clinical trial recruited women with a singleton pregnancy during November 2009 to October 2011. Exclusion criteria included respiratory disease, gestation <37 weeks and pregnancy complications. The device administered fentanyl 54 lg per spray, incorporating a 3-min lock-out. Data collected included demographics, dose, additional analgesia, adverse events, pain relief and delivery outcomes. Follow-up data were obtained within 48 h regarding tolerability of the device. Results: The final sample included 32 women: mean age was 28.7 years and gestation 39.8 weeks. Mean fentanyl dose was 734 lg and duration of use was 3.5 h. Most women (78.2%) reported satisfactory to excellent pain relief using the nasal device. Four neonates (12.5%) required bag-mask ventilation at birth: three had adequate respiration within 5 min and one required short-term observation in the special-care nursery. For all items, there was a trend towards an adverse outcome, including neonatal respiratory support, as the dose of fentanyl increased. On follow-up, 84.4% reported they would use intranasal fentanyl for their next childbirth experience. Conclusions: Patient-controlled intranasal fentanyl provides an acceptable level of analgesia during childbirth. It may, however, increase the risk of neonatal respiratory depression. Future, randomised studies should evaluate the safety and efficacy of patient-controlled intranasal fentanyl compared with existing analgesia options.

Intranasal naloxone for the treatment of suspected heroin overdose

AIMS: This paper reviews available literature regarding the effectiveness, safety and utility of intranasal (i.n.) naloxone for the treatment of heroin overdose.

METHODS: Scientific literature in the form of published articles during the period January 1984 to August 2007 were identified by searching several databases including Medline, Cinahl and Embase for the following terms: naloxone, narcan, intranasal, nose. The data extracted included study design, patient selection, numbers, outcomes and adverse events.

RESULTS: Reports of the pharmacological investigation and administration of i.n. naloxone for heroin overdose are included in this review. Treatment of heroin overdose by administration of i.n. naloxone has been introduced as first-line treatment in some jurisdictions in North America, and is currently under investigation in Australia.

CONCLUSION: Currently there is not enough evidence to support i.n. naloxone as first-line intervention by paramedics for treatment of heroin overdose in the pre-hospital setting. Further research is required to confirm its clinical effectiveness, safety and utility. If proved effective, the i.n. route may be useful for drug administration in community settings (including peer-based administration), as it reduces risk of needlestick injury in a population at higher risk of blood-borne viruses. Problematically, naloxone is not manufactured currently in an ideal form for i.n. administration.