Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority phase 3 trial

PURPOSE: Subcutaneous APF530 provides controlled sustained release of granisetron to prevent acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). This randomized, double-blind phase 3 trial compared APF530 and palonosetron in preventing acute and delayed CINV after moderately (MEC) or highly emetogenic chemotherapy (HEC). METHODS: Patients receiving single-day MEC or HEC received single-dose APF530 250 or 500 mg subcutaneously (SC) (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg. Primary objectives were to establish APF530 noninferiority to palonosetron for preventing acute CINV following MEC or HEC and delayed CINV following MEC and to determine APF530 superiority to palonosetron for preventing delayed CINV following HEC. The primary efficacy end point was complete response (CR [using CI difference for APF530 - palonosetron]). A lower confidence bound greater than -15 % indicated noninferiority. RESULTS: In the modified intent-to-treat population (MEC = 634; HEC = 707), both APF530 doses were noninferior to palonosetron in preventing acute CINV after MEC (CRs 74.8 % [-9.8, 9.3] and 76.9 % [-7.5, 11.4], respectively, vs. 75.0 % palonosetron) and after HEC (CRs 77.7 % [-11.5, 5.5] and 81.3 % [-7.7, 8.7], respectively, vs. 80.7 % palonosetron). APF530 500 mg was noninferior to palonosetron in preventing delayed CINV after MEC (CR 58.5 % [-9.5, 12.1] vs. 57.2 % palonosetron) but not superior in preventing delayed CINV after HEC. Adverse events were generally mild and unrelated to treatment, the most common (excluding injection-site reactions) being constipation. CONCLUSIONS: A single subcutaneous APF530 injection offers a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC

MRI Acquisition and Analysis Protocol for In Vivo Intraorbital Optic Nerve Segmentation at 3T

Purpose.: To present a new acquisition and analysis protocol for reliable and reproducible segmentation of the entire intraorbital optic nerve (ION) mean cross-sectional area by means of magnetic resonance imaging (MRI) at 3 tesla (T). / Methods.: Eight healthy volunteers (mean age 31, five were male) gave written informed consent and both of their IONs were imaged individually using a coronal-oblique T2-weighted fast multidynamic image acquisition scheme; the proposed acquisition scheme has its rationale in combining separately acquired volumes and registering them to account for motion-related artifacts commonly associated with longer acquisitions. Mean cross-sectional area of each ION was measured using a semiautomated image analysis protocol that was based on an active surface model previously described and used for spinal cord imaging. Reproducibility was assessed for repeated scans (scan-rescan) and repeated image analysis performance (intraobserver). / Results.: Mean and SD values of the left ION cross-sectional area for the eight healthy volunteers were 5.0 (±0.7) mm2 and for the right ION were 5.3 (±0.8) mm2. Mean scan-rescan coefficient of variation (COV) for the left ION was 4.3% and for the right was 4.4%. Mean intraobserver COV for the left ION was 2.1% and for the right was 1.8%. / Conclusions.: This study presents a new MRI acquisition and analysis protocol for reliable and reproducible in vivo measurement of the entire ION mean cross-sectional area as demonstrated in a pilot study of healthy subjects. The protocol presented here can be used in future studies of the ION in disease state

Neurofilament results for the phase II neuroprotection study of phenytoin in optic neuritis

Background: A randomized trial of phenytoin in acute optic neuritis (ON) demonstrated a 30% reduction in retinal nerve fiber layer (RNFL) loss with phenytoin versus placebo. Here we present the corresponding serum neurofilament analyses. Methods: Eighty-six acute ON cases were randomized to receive phenytoin (4–6 mg/kg/day) or placebo for 3 months, and followed up for 6 months. Serum was collected at baseline, 3 and 6 months for analysis of neurofilament heavy chain (NfH) and neurofilament light chain (NfL). Results: Sixty-four patients had blood sampling. Of these, 58 and 56 were available at 3 months, and 55 and 54 were available at 6 months for NfH and NfL, respectively. There was no significant correlation between serum NfH and NfL at the time points tested. For NfH, the difference in mean placebo – phenytoin was −44 pg/ml at 3 months (P = 0.019) and −27 pg/ml at 6 months (P = 0.234). For NfL, the difference was 1.4 pg/ml at 3 months (P = 0.726) and −1.6 pg/ml at 6 months (P = 0.766). Conclusions: At 3 months, there was a reduction in NfH, but not NFL, in the phenytoin versus placebo group, while differences at 6 months were not statistically significant. This suggests a potential neuroprotective role for phenytoin in acute ON, with the lower NfH at 3 months, when levels secondary to degeneration of the anterior visual pathway are still elevated, but not at 6 months, when levels have normalized

Physicochemical and Biological Characterisation of Diclofenac Oligomeric Poly(3-hydroxyoctanoate) Hybrids as β-TCP Ceramics Modifiers for Bone Tissue Regeneration

Nowadays, regenerative medicine faces a major challenge in providing new, functional materials that will meet the characteristics desired to replenish and grow new tissue. Therefore, this study presents new ceramic-polymer composites in which the matrix consists of tricalcium phosphates covered with blends containing a chemically bounded diclofenac with the biocompatible polymer-poly(3-hydroxyoctanoate), P(3HO). Modification of P(3HO) oligomers was confirmed by NMR, IR and XPS. Moreover, obtained oligomers and their blends were subjected to an in-depth characterisation using GPC, TGA, DSC and AFM. Furthermore, we demonstrate that the hydrophobicity and surface free energy values of blends decreased with the amount of diclofenac modified oligomers. Subsequently, the designed composites were used as a substrate for growth of the pre-osteoblast cell line (MC3T3-E1). An in vitro biocompatibility study showed that the composite with the lowest concentration of the proposed drug is within the range assumed to be non-toxic (viability above 70%). Cell proliferation was visualised using the SEM method, whereas the observation of cell penetration into the scaffold was carried out by confocal microscopy. Thus, it can be an ideal new functional bone tissue substitute, allowing not only the regeneration and restoration of the defect but also inhibiting the development of chronic inflammation

A prospective cohort study of postoperative complications in the management of perforated peptic ulcer

BACKGROUND: With dwindling rates of postoperative mortality in perforated peptic ulcer that is attributable to H(2)-receptor blocker usage, there is a need to shift the focus towards the prevention of postoperative morbidity. Further, the simultaneous contribution of several putative clinical predictors to this postoperative morbidity is not fully appreciated. Our objective was to assess the predictors of the risk, rate and number of postoperative complications in surgically treated patients of perforated peptic ulcer. METHODS: In a prospective cohort study of 96 subjects presenting as perforated peptic ulcer and treated using Graham's omentoplatsy patch or gastrojejunostomy (with total truncal vagotomy), we assessed the association of clinical predictors with three domains of postoperative complications: the risk of developing a complication, the rate of developing the first complication and the risk of developing higher number of complications. We used multiple regression methods – logistic regression, Cox proportional hazards regression and Poisson regression, respectively – to examine the association of the predictors with these three domains. RESULTS: We observed that the risk of developing a postoperative complication was significantly influenced by the presence of a concomitant medical illness [odds ratio (OR) = 8.9, p = 0.001], abdominal distension (3.8, 0.048) and a need of blood transfusion (OR = 8.2, p = 0.027). Using Poisson regression, it was observed that the risk for a higher number of complications was influenced by the same three factors [relative risk (RR) = 2.6, p = 0.015; RR = 4.6, p < 0.001; and RR = 2.4, p = 0.002; respectively]. However, the rate of development of complications was influenced by a history suggestive of shock [relative hazards (RH) = 3.4, p = 0.002] and A(- )blood group (RH = 4.7, p = 0.04). CONCLUSION: Abdominal distension, presence of a concomitant medical illness and a history suggestive of shock at the time of admission warrant a closer and alacritous postoperative management in patients of perforated peptic ulcer

A randomised phase II study of weekly paclitaxel or vinorelbine in combination with cisplatin against inoperable non-small-cell lung cancer previously untreated

[[abstract]]Phase II studies have suggested that weekly paclitaxel has a higher response rate and better toxicity profile than the conventional schedule of once every 3 or 4 weeks. Our aim was to evaluate the efficacy of weekly paclitaxel plus cisplatin (PC) vs vinorelbine plus cisplatin (VC) in chemonaive non-small-cell lung cancer (NSCLC) patients. From October 2000 to May 2002, 140 patients were enrolled. The treatment dose was P 66 mg m(-2) intravenous infusion (im.) on days 1, 8, and 15, and C 60 mg m(-2) i.v. on day 15, or V 23 mg m(-2) i.V. on days 1, 8, and 15, and C 60 mg m(-2) i.v. on day 15, every 4 weeks. In all, 28 1 cycles of PC and 307 cycles of VC were given to the patients in the PC and VC arms, respectively. There were 26 partial responses and one complete response (overall 38.6%) in the PC arm, and no complete responses, but 27 partial responses (overall 38.6%) in the VC arm. Myelosuppression was more common in the VC arm (P<0.001). Peripheral neuropathy and myalgia were significantly more common in the PC arm (P<0.001). The median time to disease progression was 6 months in the PC arm and 8.4 months in the VC arm (P=0.0344). The median survival time was 11.7 months in the PC arm and 15.4 months in the VC arm (P = 0.297). We concluded that weekly PC is not suggested for NSCLC patients due to the relatively shorter progression-free survival and more common nonhaematological toxicities

Becoming Physically Active After Bariatric Surgery is Associated With Improved Weight Loss and Health-Related Quality of Life

The purpose of this study was to determine whether pre- to postoperative increases in physical activity (PA) are associated with weight loss and health-related quality of life (HRQoL) following bariatric surgery. Participants were 199 Roux-en-Y gastric bypass (RYGB) surgery patients. The International Physical Activity Questionnaire (IPAQ) was used to categorize participants into three groups according to their preoperative and /1-year postoperative PA level: (i) Inactive/Active (\u3c200-min/week/≥200-min/week), (ii) Active/Active (≥200-min/week/greater ≥200-min/week) and (iii) Inactive/Inactive (\u3c200-min/week/\u3c200-min/week). The Medical Outcomes Study Short Form-36 (SF-36) was used to assess HRQoL. Analyses of covariance were conducted to examine the effects of PA group on weight and HRQoL changes. Inactive/Active participants, compared with Inactive/Inactive individuals, had greater reductions in weight (52.5 ± 15.4 vs. 46.4 ± 12.8 kg) and BMI (18.9 ± 4.6 vs. 16.9 ± 4.2 kg/m2). Weight loss outcomes in the Inactive/Active and Active/Active groups were similar to each other. Inactive/Active and Active/Active participants reported greater improvements than Inactive/Inactive participants on the mental component summary (MCS) score and the general health, vitality and mental health domains (P \u3c 0.01). Although the direction of causation is not clear, these findings suggest that RYGB patients who become active postoperatively achieve weight losses and HRQoL improvements that are greater than those experienced by patients who remain inactive and comparable to those attained by patients who stay active. Future randomized controlled trials should examine whether assisting patients who are inactive preoperatively to increase their PA postoperatively contributes to optimization of weight loss and HRQoL outcomes