Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy.

BACKGROUND: This investigator-initiated trial provided the justification for the phase III GRID study resulting in worldwide regulatory approval of regorafenib as a third-line therapy for patients with metastatic gastrointestinal stromal tumors (GIST). We report the genotype analyses, long-term safety, and activity results from this initial trial of regorafenib in GIST. PATIENTS AND METHODS: The trial was conducted between February 2010 and January 2014, among adult patients with metastatic GIST, after failure of at least imatinib and sunitinib. Patients received regorafenib orally, 160 mg once daily, days 1-21 of a 28-day cycle. Clinical benefit rate (CBR), defined as complete or partial response (PR), or stable disease lasting ≥16 weeks per RECIST 1.1, progression-free survival (PFS), overall survival (OS), long-term safety data, and metabolic response by functional imaging were assessed. RESULTS: Thirty-three patients received at least one dose of regorafenib. The median follow-up was 41 months. CBR was documented in 25 of 33 patients [76%; 95% confidence interval (CI) 58% to 89%], including six PRs. The median PFS was 13.2 months (95% CI 9.2-18.3 months) including four patients who remained progression-free at study closure, each achieving clinical benefit for more than 3 years (range 36.8-43.5 months). The median OS was 25 months (95% CI 13.2-39.1 months). Patients whose tumors harbored a KIT exon 11 mutation demonstrated the longest median PFS (13.4 months), whereas patients with KIT/PDGFRA wild-type, non-SDH-deficient tumors experienced a median 1.6 months PFS (P < 0.0001). Long-term safety profile is consistent with previous reports; hand-foot skin reaction and hypertension were the most common reasons for dose reduction. Notably, regorafenib induced objective responses and durable benefit in SDH-deficient GIST. CONCLUSIONS: Long-term follow-up of patients with metastatic GIST treated with regorafenib suggests particular benefit among patients with primary KIT exon 11 mutations and those with SDH-deficient GIST. Dose modifications are frequently required to manage treatment-related toxicities. CLINICAL TRIAL NUMBER: NCT01068769.

Impact of contact precautions on falls, pressure ulcers and transmission of MRSA and VRE in hospitalized patients.

BACKGROUND: Hospitals use contact precautions to prevent the spread of meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). There is concern that contact precautions may have adverse effects on the safety of isolated patients. In November 2010, the infection control policy at an academic medical centre was modified, and contact precautions were discontinued for patients colonized or infected with MRSA or VRE (MRSA/VRE patients). AIM: To assess the rates of falls and pressure ulcers among MRSA/VRE patients and other adult medical-surgical patients, as well as changes in MRSA and VRE transmission before and after the policy change. METHODS: A single-centre retrospective hospital-wide cohort study was performed from 1st November 2009 to 31st October 2011. FINDINGS: Rates of falls and pressure ulcers were significantly higher among MRSA/VRE patients compared with other adult medical-surgical patients before the policy change (falls: 4.57 vs 2.04 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.87 vs 1.22 per 1000 patient-days, P < 0.0001) and after the policy change (falls: 4.82 vs 2.10 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.17 vs 1.19 per 1000 patient-days, P < 0.0001). No significant differences in the rates of falls and pressure ulcers among MRSA/VRE patients were found after the policy change compared with before the policy change. There was no overall change in MRSA or VRE hospital-acquired transmission. CONCLUSION: MRSA/VRE patients had higher rates of falls and pressure ulcers compared with other adult medical-surgical patients. Rates were not affected by removal of contact precautions, suggesting that other factors contribute to these complications. Further research is required among this population to prevent complications.

Manual corneal thickness measurements of healthy equine eyes using a portable spectral-domain optical coherence tomography device.

REASONS FOR PERFORMING STUDY: Corneal thickness measurements of the equine globe using spectral-domain optical coherence tomography (SD-OCT) have not been reported. OBJECTIVES: To determine corneal thickness measurements and the intra- and interoperator reliability of a portable SD-OCT device in equine eyes. STUDY DESIGN: Prospective observational study. METHODS: Horses free of ocular disease were used for this study. Gentle manual restraint, in combination with detomidine hydrochloride and a head stand, were employed to ensure proper animal positioning. Corneal pachymetry measurements were obtained from both eyes of each animal 3 times by 2 operators in succession. A 6 mm corneal pachymetry protocol was performed using a portable SD-OCT device. All measurements were obtained manually by one operator (C.G.P.) using the integrated calliper function. Measurements included epithelial thickness, stromal thickness, Descemet's membrane thickness and total corneal thickness. All recorded measurements were analysed to determine both intra- and interoperator reliability. RESULTS: Thirty horses with a mean age of 10.6 ± 6.4 years were examined. Mean epithelial, stromal, Descemet's membrane and total corneal thickness values obtained were, respectively, 174.7 ± 13.6, 599.2 ± 45.4, 38.4 ± 15.3 and 812.0 ± 44.1 µm for operator A and 175.9 ± 12.9, 599.2 ± 44.9, 38.4 ± 15.0 and 812.9 ± 42.9 µm for operator B. A positive correlation was found between Descemet's membrane thickness and age, whereby Descemet's membrane thickness increased by 2 µm/year (P<0.0001). The coefficients of variation for both operators were <4% for all measurements. Intraclass correlations ranged from 0.92 to 0.98. CONCLUSIONS: Manual corneal thickness measurement using a portable SD-OCT device provides epithelial, stromal, Descemet's membrane and total corneal thickness measurements with clinically acceptable intra- and interoperator reliability in healthy equine eyes.