BackgroundRepeated 5FU infusers’ preparations expose pharmacy technicians to risk of musculoskeletal disorders. To simplify the preparation of infusers in 2 days, the installation of a pump is ...envisaged. To facilitate this new method of production, standardised dose prescription has been initiated in agreement with oncologists.PurposeThe aim of this work is to qualify the pump-preparing infusers after defining standardised doses.Material and methodsAn extraction of prescribed doses of 5FU in infusers was realised over 6 months to define standardised doses. A qualification of the pump IMF is performed in the laboratory with 250 ml water bottles and 250 ml NaCl pockets used as solvent. A measure of infusers’ masses before and after injections by the pump was carried out. Accuracy was measured for four precise volumes by counting recovery rates. Repeatability (RP) was determined for the same four volumes by six repetitions performed on the same day. Finally, the intermediate fidelity (FI) was defined for these four volumes by three repetitions carried out on three consecutive days.ResultsIn the end, four 5FU doses were selected after discussion with oncologists: 3,700, 4,100, 4400 and 4,600 mg with an error of ±5% targeting an interval of patients between 1.5 and 1.9 m². Of the 475 infusers’ doses analysed, dose standardisation accounted for 72% of 5FU infuser production in 2 days. During this study, 36 preparations were created with volumes of water between 74 and 92 ml. Volumes are repeatable and accurate from 74 ml (3,700 mg) to 92 ml (4,600 mg) with a coefficient of variation <2%. The accuracy of filling is included within the limit of +/–2% for each dose.ConclusionThe IMF pump is accurate, repeatable and faithful for preparation of diffuser doses of 5FU between 3700 and 4,600 mg. This H2O2 sterilizable pump can be easily integrated into an isolator. This method qualification must be verified under an isolator with 5FU.Reference and/or Acknowledgements1. Preliminary study for the implementation of standardised rounded doses of cytotoxic druqs. J Pharm Belg 2015 Sep;(3):24–35. French.No conflict of interest
Abstract
Background
Breast cancer is associated with a high 5-year survival rate and more than half women are still of working age at diagnosis. Many studies evaluated the clinical determinants of ...return to work (RTW) but few investigated RTW in relation to family factors. Our objective was to study the role of household characteristics in non-RTW two years after breast cancerdiagnosis.
Methods
We used data of a French prospective cohort of women diagnosed with stage I-III, primary breast cancer (CANTO, NCT01993498). Patients had to be under 57 and have a job at diagnosis. We performed logistic regressions to model non-RTW two years after diagnosis in relation to household characteristics at diagnosis (marital status, children, support from partner), adjusting for tumor characteristics, health status at baseline and one year after diagnosis, and household income at diagnosis. In a second step, we conducted analyses stratified for household income at diagnosis.
Results
In total, 1874 women were eligible. Being in a relationship did not impact non-RTW (OR = 1.43 95% CI 0.95-2.16). Among the 1566 women in a relationship, being married was associated with elevated odds of non-RTW(OR = 1.37 0.96-1.94). Having children(OR = 1.17 0.81-1.69) or receiving support from their partner (OR = 1.17 0.77-1.78) was not associated with non-RTW. However, the situation differed in low-income households(<2500€) among whom being married was associated with more elevated odds of non-RTW(OR = 1.94 0.97-3.88). No clear association was observed between having children (OR = 1.85 0.85-4.03) and non-RTW, but living with at least two children (OR = 2.76 1.14-6.70) and receiving support from their partner (OR = 2.28 1.01-5.17) was associated with increased odds of non-RTW.
Conclusions
The family environment is associated with non-RTW among the poorest women but not the others.
Key messages
Among the poorest women, the family environment is associated with non-RTW.
Among all women, the family environment is not associated with non-RTW.
Cell–cell adhesion mediated by cadherins is believed to play an essential role in the control of cell differentiation and tissue formation. Our recent studies indicate that N-cadherin is involved in ...human osteoblast differentiation. However, the signalling molecules that regulate cadherins in osteoblasts are not known. We tested the possibility that N-cadherin expression and function may be regulated by direct activation of protein kinase C (PKC) in human osteoblasts. Treatment of immortalized human neonatal calvaria (IHNC) cells with phorbol 12,13-dibutyrate (100 nM) transiently increased PKC activity. RT-PCR analysis showed that transient treatment with phorbol ester transiently increased N-cadherin mRNA levels at 4–12 h. Western blot analysis showed that N-cadherin protein levels were increased by phorbol ester at 24–48 h, and this was confirmed by immunocytochemical analysis. In contrast, E-cadherin expression was not affected. Transient treatment of IHNC cells with phorbol ester increased cell–cell aggregation, which was suppressed by neutralizing N-cadherin antibody, showing that the increased N-cadherin induced by phorbol ester was functional. Finally, phorbol ester dose-dependently increased alkaline phosphatase activity, an early marker of osteoblast differentiation. This effect was comparable to the promoting effect of BMP-2, a potent activator of osteoblast differentiation. These data show that direct activation of PKC by phorbol ester increases N-cadherin expression and function, and promotes ALP activity in human calvaria osteoblasts, which provides a signaling mechanism by which N-cadherin is regulated and suggests a role for PKC in N-cadherin-mediated control of human osteoblast differentiation.
BackgroundHeart failure (HF) is a major public health concern, affecting 26 million people worldwide. The association sacubitril/valsartan was marketed for the treatment of chronic HF. In the ...PARADIGM-HF-trial, Entresto has shown a reduction of HF admissions and cardiovascular mortality significantly higher than standard recommended treatment.1 The most significant shortcoming of this study was the population included (younger and less severe).PurposeThe aim of our study was to compare characteristics of a patient cohort followed-up in a hospital centre with patients in the PARADIGM-HF trial. Other objectives were to estimate the incidence of HF hospitalisation of patients treated by Entresto and identify adverse events.Material and methodsA prospective study was conducted from January to December 2017. An extraction of Entresto ambulatory dispensations during this period was carried out. A selection of patients followed-up in our hospital was made. Data were collected in patient medical files. A statistical comparison between collected data and data from the PARADIGM-HF trial was done. Adverse events and the incidence of unexpected hospitalisations were listed.ResultsForty HF patients were retrospectively studied. Our patients were older and had a higher NYHA class than in the PARADIGM-HF trial (p<0.05), however fewer comorbidities have been identified (p<0.05) and fewer patients were pretreated by ACEI and beta-blockers (p<0.05 for both). Similar adverse events have been reported: arterial hypotension (17.5%), hyperkalaemia (22%), kidney failure (7.5%) and cough (2.5%). Other adverse events have been reported such as hypokalaemia (5.5%) and cardiac decompensation (35%). Thirteen patients were hospitalised in the cardiology care unit for at least one HF decompensation.ConclusionDespite the low total headcount of patients in this study, the difference between baseline characteristics have been shown. Patients were older and had a higher NYHA class which may explain that 13 of 40 patients were hospitalised for at least one HF episodes. The occurrence of adverse effects can explain that patients were treated with a lower dosage of Entresto, only 22% reached maximal dosage (97/103 mg). An investigation needs to be done to compare hospitalisations of patients before and after the introduction of Entresto, to show its the real impact.Reference and/or acknowledgementsMcMurray, et al. NEJM 2014.No conflict of interest.
PDF
