FORMULATION AND EVALUATION OF CONTROLLED POROSITY OSMOTIC PUMP TABLETS OF GLIMEPIRIDE

A Controlled porosity of the membrane is accomplished by the use of pore former. The usual dose of glimepiride was 4 mg to be taken twice daily. The plasma half life of glimepiride was 5 h. Hence, glimepiride was chosen as a model drug with an aim to develop a controlled release system for 24 h. Sodium chloride was use as osmogent. Cellulose acetate was used as the semi permeable membrane. The porous osmotic pump contains pore forming water-soluble additive (Poly ethylene glycol 400) in the coating membrane which after coming in contact with water, dissolve, resulting in an in situ formation of microporous structure. The effect of different formulation variables, namely, ratio of drug to osmogent, membrane weight gain and concentration of pore former on the in vitro release was studied using 23 full factorial design. The effect of pH and agitation intensity on drug release was also studied. It was found that drug release rate increased with the amount of osmogent because of increased water uptake. Drug release was inversely proportional to membrane weight gain. Surface plot is also presented to graphically represent the effect of independent variables on t90. Optimized formulation was found to release above 90% of glimepiride at a zero order rate for 24 h

Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2410160

Implementation of treatment escalation plans in an old age psychiatry inpatient hospital

A Treatment Escalation Plan (TEP) enables timely and appropriate decision making in the management of deteriorating patients. The COVID-19 pandemic precipitated the widespread use of TEPs in acute care settings throughout the National Health Service (NHS) to facilitate safe and effective decision making. TEP proformas have not been developed for the inpatient psychiatric setting. This is particularly concerning in Old Age Psychiatry inpatient wards where patients often have multiple compounding comorbidities and complex decisions regarding capacity are often made.Our aim for this quality improvement project was to pilot a novel TEP proforma within a UK Old Age Psychiatry inpatient hospital. We first adapted a TEP proforma used in our partner acute tertiary hospital and implemented it on our Old Age Psychiatry wards. We then further refined the form and gathered data about uptake, length of time to complete a TEP and the ceiling of care documented in the TEP. We also explored staff, patient and family views on the usefulness of TEP proformas using questionariesTEP decisions were documented in 54% of patient records at baseline. Following revision and implementation of a TEP proforma this increased to 100% on our two wards. The mean time taken to complete a TEP was reduced from 7.1 days to 3.2 days following inclusion of the TEP proforma in admission packs. Feedback from staff showed improvements in understanding about TEP and improved knowledge of where these decisions were documented.We advocate the use of TEP proformas on all Old Age Psychiatry inpatient wards to offer clear guidance to relatives and treating clinicians about the ceilings of care for patients. There are potentially wider benefits to healthcare systems by reducing inappropriate transfers between Psychiatry and acute NHS hospitals.<br/

A20/TNFAIP3, a new estrogen-regulated gene that confers tamoxifen resistance in breast cancer cells

The zinc-finger protein A20/TNFAIP3, an inhibitor of nuclear factor-kappaB (NF-kappaB) activation, has been shown to protect MCF-7 breast carcinoma cells from TNFalpha-induced apoptosis. As estrogen receptor (ER) status is an important parameter in the development and progression of breast cancer, we analysed the effect of 17beta-estradiol (E2) treatment on the expression of A20. We found that A20 is a new E2-regulated gene, whose expression correlates with ER expression in both cell lines and tumor samples. With the aim of investigating the impact of A20 expression on MCF-7 cells in response to ER ligands, we established stably transfected-MCF-7 cells overexpressing A20 (MCF-7-A20). These cells exhibited a phenotype of resistance to the 4-hydroxy-tamoxifen cytostatic and pro-apoptotic actions and of hyper-response to E2. Dysregulations in bax, bcl2, bak, phospho-bad, cyclin D1, cyclin E2, cyclin D2 and cyclin A2 proteins expression were shown to be related to the resistant phenotype developed by the MCF-7-A20 cells. Interestingly, we found that A20 was also overexpressed in MVLN and VP tamoxifen-resistant cell lines. Furthermore, high A20 expression levels were observed in more aggressive breast tumors (ER-negative, progesterone receptor-negative and high histological grade). These overall findings strongly suggest that A20 is a key protein involved in tamoxifen resistance, and thus represents both a new breast cancer marker and a promising target for developing new strategies to prevent the emergence of acquired mechanisms of drug resistance in breast cancer

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

Introduction: Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. Methods: This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18–49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54–5.02), frailty (CFS 8 versus 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1–3: odds ratio 7.00, CI 5.27–9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusion: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.</p