Implementation of an ultrasound-guided approach for arterial line placements in neonates-quality improvement project.

OBJECTIVE: Our goal was to improve placement success rates for peripheral arterial line (PAL) placements by introducing an ultrasound-guided (USg) approach. Our aim was to maintain success rates over 70% within 18 months. STUDY DESIGN: Interventions included development of a training curriculum, and procedure standardization. Among 302 patients, 115 underwent USg catheter placement; the traditional method was used in 187 patients. Outcome measures were first-attempt and overall success rates. Process measures were proportion of PALs placed under US guidance, trainer availability, and trainee sign-off. Line complications were balancing measures. Statistical process control charts were used to monitor metrics. RESULTS: Sustained improvement was seen with the USg approach. The USg approach had first and overall attempt success by the trainers (i.e., independent users) of 83.7% (77/92) and 96.5% (111/115), compared to 50.3% (82/163) and 73.8% (138/187) with the traditional approach. CONCLUSION: Introducing the USg approach had a significant impact on PAL placement success in neonatal patients.

Sequential chemotherapy followed by radical thoracic radiotherapy (50 Gy in 25 fractions) in limited stage small cell lung cancer.

INTRODUCTION: For limited stage small cell lung cancer (LS-SCLC) where concurrent chemoradiotherapy is inappropriate due to tumour bulk, co-morbidities or performance status, sequential treatment using chemotherapy followed by radiotherapy is the standard of care. The outcomes are not well established; we assessed in a single institution, the survival of these patients, prognostic factors and compared to the limited existing literature. MATERIALS AND METHOD: Retrospective data was collected on all 59 patients diagnosed with LS-SCLC from 2011 to 2016 who received chemotherapy consisting of Carboplatin or Cisplatin + Etoposide followed by thoracic radiotherapy (50 Gy in 25 fractions) +/- prophylactic cranial irradiation (PCI). RESULTS: Median age at diagnosis was 66 years (range 46-90). Patients received a median of four cycles of chemotherapy (range: 1-6) and all the patients completed a full course of radiotherapy with only one patient experiencing grade >2 radiation induced toxicity. With a median follow up of 20.6 months, 45 patients had died with a median survival of 20.6 months. 2-year overall survival (OS) rates were 42%. Age using a cut-off of 65 was prognostic (median OS 25.6 months ≤65 years versus 14.1 months >65 years, p = 0.013) but gender, stage and receipt of PCI were not. CONCLUSIONS: Most of the literature reporting outcome from sequential treatment in LS-SCLC is old and used a variety of radiotherapy regimens. Our data shows inferior outcomes to the gold standard concurrent chemoradiotherapy but support its usage in less fit patients with reasonable outcome observed.

Overlapping HIV prevention strategies; case report of pre-exposure and postexposure prophylaxes used for a single risk event between two men.

A range of prevention strategies have been considered in an attempt to reduce HIV transmission. The use of continuous antiretrovirals (ARVs) in high-risk HIV-negative individuals (pre-exposure prophylaxis or PrEP) and the short-term use of ARVs following a high-risk exposure (postexposure prophylaxis or PEP) are among these strategies. We report a case of the contemporaneous use of PEP and PrEP in a sexual liaison between two men.In an attempt to reduce the number of new cases of HIV infection, a range of prevention strategies have been advocated. Prior to the availability of ARV therapy, the key prevention measure was condom promotion and modifying sexual behaviour such as partner number reduction within high-risk groups. This was followed by: the introduction of PEP, treating all HIV cases with ARVs to reduce the probability of transmission (treatment as prevention) and in the past few years the use of PrEP. Case-control, observational and randomised clinical trial data exist to support these strategies. We describe what we believe is the first reported use of PrEP and PEP in a sexual liaison between two men in Sydney.

Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients.

PURPOSE: The primary objective of this study was to investigate the influence of renal impairment on the pharmacokinetics of capecitabine and its metabolites in cancer patients. Capecitabine (Xeloda) is an orally administered precursor of 5'-deoxy-5-fluorouridine (5'-DFUR), which is preferentially activated to 5-fluorouracil (5-FU) in tumors. METHODS: A total of 27 patients were enrolled, of whom 24 were evaluable for pharmacokinetics (6 with normal renal function, 8 with mild, 6 with moderate, and 4 with severe renal impairment at baseline). Patients received capecitabine orally at the standard dosing regimen (1250 mg/m(2) capecitabine twice daily for 2 weeks followed by a 1-week rest period). On study days 1 and 14, blood samples were collected to evaluate the pharmacokinetics of capecitabine and its metabolites. The relationship between the area under the plasma concentration-time curve (AUC) and creatinine clearance (CL(CR)) was assessed by log-linear regression analysis. RESULTS: The primary pharmacokinetic parameter with respect to the effect of renal dysfunction was systemic exposure to 5'-DFUR, 5-FU and FBAL determined on study day 14. Renal impairment led to an increase in the systemic exposure to 5'-DFUR and FBAL (23% and 109% increase in AUC, respectively) for a 50% reduction in CL(CR). By contrast, renal impairment may lead to decreased exposure to 5'-DFCR. There was no evidence for an effect of renal impairment on systemic exposure to 5-FU or capecitabine. Renal impairment did not have a major effect on peak concentration (C(max)) or elimination half-life (t(1/2)) of capecitabine, 5'-DFCR, 5'-DFUR, and 5-FU. However, in the case of FBAL, moderate or severe renal impairment caused up to a twofold increase in C(max) and prolongation of t(1/2). All patients with severe renal impairment (four patients) had drug-related grade 3 or 4 adverse-events (AEs) and serious AEs. Patients with moderate renal impairment experienced a similar number of grade 3 or 4 AEs (six of nine patients) but had a higher incidence of serious AEs (three of nine patients) when compared with those with normal renal function (four of six patients and one of six patients, respectively). A similar effect was seen in patients with mild renal dysfunction (grade 3 or 4 AEs in four of eight patients; serious AEs in three of eight patients). The relationship between systemic exposure to capecitabine or its metabolites and safety was investigated using logistic regression. This exploratory analysis showed a strong positive relationship between AUC of 5'-DFUR and treatment-related grade 3 or 4 AEs, whereas there was no relationship with exposure to capecitabine, 5'-DFCR, 5-FU or FBAL. CONCLUSIONS: Renal impairment has no effect on the pharmacokinetics of capecitabine or 5-FU, but leads to an increase in the systemic exposure to 5'-DFUR and FBAL. However, only the AUC of 5'-DFUR is correlated with safety. Based on the safety results in patients with severe renal impairment, a dose modification cannot be recommended for these patients and they should not be treated with capecitabine. Additional data from the clinical safety database and pharmacokinetic results from the present study support the recommendation that patients with moderate renal impairment should be treated with 75% of the recommended standard starting dose to achieve systemic exposure comparable to that in patients with normal renal function.