Influence of the punch diameter and curvature on the yield pressure of MCC-compacts during Heckel analysis.

The volume reduction behaviour of powders has been quantified by means of the 'in-die' yield pressure (YP) using Heckel analysis. However, because different YPs are reported for the same material, the experimental conditions influencing this material-constant were investigated. Silicified microcrystalline cellulose was compressed into flat-faced and convex tablets using a compaction simulator instrumented with load and displacement transducers. During compression, upper and lower punch force and displacement data were recorded and corrected for punch deformation. A symmetrical triangle wave compression profile was used and the instantaneous punch velocity was kept constant (5mm/s). Individual tablet height and weight were used for Heckel analysis. The influence of the 'effective compression pressure' (P(EFF)) (ranging from 10 to 350 MPa), punch diameter (PD) (4, 9.5 and 12 mm) and filling depth (FD) (4.5, 7.5 and 10.5mm) on YP was statistically evaluated using Response Surface Modelling software. A quadratic surface response equation, describing the relationship between P(EFF), PD, FD and YP, was proposed for concave (Adj R(2): 0.8424; S.D.: 14.60 MPa) and flat-faced (Adj R(2): 0.8409; S.D.: 4.49 MPa) punches. YP and tensile strength were mainly determined by P(EFF), irrespective of punch curvature. FD and PD had only a minor influence on the YP, although more pronounced for the concave punches. The method used resulted in reproducible P(EFF) and tensile strength values and the flat-faced tablets showed less weight variation. Flat-faced punches are preferred over punches with a concave surface when investigating the volume reduction behaviour of a powder by means of Heckel analysis and the experimental parameters should be reported.     

Identification of serious drug-drug interactions: results of the partnership to prevent drug-drug interactions.

OBJECTIVE: To develop a list of clinically important drug-drug interactions (DDIs) likely to be encountered in community and ambulatory pharmacy settings and detected by a computerized pharmacy system. DESIGN: Cross-sectional, one-time evaluation. SETTING: United States in fall 2001. PARTICIPANTS: An expert panel comprising two physicians, two clinical pharmacists, and an expert on DDIs. INTERVENTIONS: Systematic review of drug interaction compendia and published literature, ratings (on a 1 to 10 scale) of various clinical aspects of DDIs (e.g., clinical importance, quality and quantity of evidence, causal relationship, risk of morbidity and mortality), and a modified Delphi consensus-building process. MAIN OUTCOME MEASURE: Panelists' opinions about clinical importance of DDIs. RESULTS: The expert panel considered 56 DDIs. Of these, 28 had a mean clinical importance score of 8.0 or more. The ratings for clinical importance ranged from 3.2 to 9.6, with a mean +/- SD of 7.5 +/- 1.5 across the combinations examined. The mean score for the quality of literature suggesting the interaction exists ranged from 1.0 to 9.6, with a mean +/- SD of 5.8 +/- 2.5. In terms of substantiation of the interactions evaluated, the mean +/- SD rating was 6.3 +/- 2.2, with a range from 1.4 to 9.2. Through the modified Delphi process, the panel determined that 25 interactions were clinically important. CONCLUSION: Using an expert panel and a standard evaluation tool, 25 clinically important drug interactions that are likely to occur in the community and ambulatory pharmacy settings were identified. Pharmacists should take steps to prevent patients from receiving these interacting medications, and computer software vendors should focus interaction alerts on these and similarly important DDIs.     

Stapled versus hand-sewn vascular anastomoses. An experimental study in the rabbit

OBJECTIVE: Narrowing of vascular anastomoses is a frequently encountered surgical problem, with intimal hyperplasia being one of its most important causes. The aim of the present study was to compare in a rabbit model 'manual' (hand-sewn) with 'stapled' anastomoses (using a staple device) with respect to occurrence and severity of intimal hyperplasia. MATERIALS AND METHODS: Twenty-four male rabbits (mean weight 2,849 g) were randomly allocated to one of two groups (n = 12). An end-to-end anastomosis of the left femoral artery was performed in all animals under general anesthesia. The anastomosis was hand sewn in group 1, while a vascular closure stapler (VCS) was used in group 2. Both anastomotic time and total operation time were recorded. After 28 days, the rabbits were sacrificed. The femoral artery of operated and nonoperated sides were removed and prepared for anatomopathological examination. The I/M ratio (= difference between tunica intima and tunica media) was determined on hematoxylin-eosin stained slides. All results were analyzed using Student's t test. RESULTS: Mean anastomotic times were 25 +/- 7 min for the 'manual' group and 17 +/- 9 min for the 'stapled' group (p = 0.02). There was no significant difference in the total operation time (55 +/- 15 vs. 41 +/- 18 min, p = 0.057). All animals survived the anastomosis procedure. In the group of 'manual' anastomosis, morbidity was significantly higher. At the moment of sacrifice, all anastomoses were patent. There was no difference in the I/M ratio between the groups. CONCLUSIONS: The use of VCS is a promising alternative to hand-sewn anastomoses. It takes less time to perform a stapled anastomosis, the technique has a shorter learning period and morbidity seems to be lower when vascular anastomoses are applied with the VCS in this rabbit model.     

First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study

Background Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results.Methods TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m² orally twice daily on days 1–5 and 8–12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m² orally twice daily on days 1–14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS.Results At 1 September 2020, median OS was 22.3 months (95% CI: 18.0–23.7) with TT-B and 17.7 months (95% CI: 12.6–19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55–1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings.Conclusions TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy.Clinical trial information {"type":"clinical-trial","attrs":{"text":"NCT02743221","term_id":"NCT02743221"}}NCT02743221 (clinicaltrials.gov)Subject terms: Colorectal cancer, Colorectal cancer     

Prediction of acute stroke progression by the National Institutes of Health Stroke Scale

Objective To determine the occurrence of neurological changes during the first 48 hours after acute stroke as it relates to the initial stroke severity assessment. Methods The assessment with the National Institutes of Health Stroke Scale (NIHSS) was performed serially for the first 48 hours on 68 consecutive ischemic stroke patients admitted to the Department of Geriatric Cardiology at the Khanh Hoa Hospital, Nha Trang, Vietnam. Incidence of stroke progression (a ≥ 3-point increase on the NIHSS) was recorded and analysis performed to determine its association with initial stroke severity and other demographic and physiological variables. Deficit resolution by 48 hours, defined as an NIHSS score of 0 or 1, measured the frequency of functional recovery predicted by the initial deficit. Results Overall progression was noted in 28% of events (19/68). Applying Bayes' solution to the observed frequency of worsening, the greatest likelihood of predicting future patient progression occurred with NIHSS score of =7 and >7. Patients with an initial NIHSS score of =7 experienced a 13% (6/47) worsening rate versus those of an initial score of >7 with a 62% (13/21) worsening rate (P<0.01). 42.5% (20/47) of those with an initial score of =7 were functionally normal at 48 hours, whereas only 4.7% (1/21) of those with scores of >7 returned to a normal examination within this period (χ2, P<0.05). Conclusions This study suggests that the early clinical course of neurological deficit after acute stroke be dependent on the initial stroke severity and that a dichotomy in early outcome exist surrounding an initial NIHSS score of 7. These findings may have significant implications for the design and patient stratification in treatment protocols with respect to primary clinical outcome.(J Geriatr Cardiol 2007;4:225-228.)     

Reliability of clinical oral examinations re-examined

Many medical schools still use oral examinations for the evaluation of clinical competence of students in their clerkship, although it has been proven that orals have poor reliability. This study investigates the feasibility and reliability of multiple oral examinations. Students in the last week of their Internal Medicine clerkship in an outpatient clinic were given several patient-based oral examinations. The student's performance was rated on a list of items reflecting clinical competence. A global judgement of the student's performance was also given. The results indicate that it is possible to increase the number of orals and the number of examiners in the day-to-day practice of an outpatient clinic moderately. The reliability when using a number of orals is better than the reliability of the common single oral examination. The reliability using global judgements appeared to be better than the reliability of averaged item scores.     

Chemical constituents and biological activities of Zanthoxylum usambarense.

Bioassay-guided fractionation of the dichloromethane extracts of the roots and the bark of Zanthoxylum usambarense led to the isolation of two physiologically active compounds, i.e. canthin-6-one 1 (fungicide) and pellitorine 4 (insecticide). Together with oxychelerythrine 2, norchelerythrine 3, (+)-sesamin 5 and (+)-piperitol-3,3-dimethylallyl ether 6, they were isolated for the first time from this plant.