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Author : Secher Craft | Published On : 10 May 2025
tmenopausal BC patients. AI-based ET remains the treatment of choice for postmenopausal BC patients with HR-positive disease in the modern era of HER2-directed therapy irrespective of HER2-status.The need for drug-related safety warnings is undisputed, but their impact on prescribing behaviour is not always clear. Safety warnings usually do not contain therapeutic alternatives. Based on German outpatient routine healthcare data, our cohort study investigated the impact of three warnings for fluoroquinolones on prescribing behaviour.
Structural breaks were estimated in a time-series analysis (2005-2014) of 184,134 first antibiotic prescriptions for patients (≥ 18years) diagnosed with community-acquired pneumonia (CAP), acute bacterial sinusitis (ABS), or acute exacerbation of chronic bronchitis (AECB). Subsequently, risk factors for patients' before/after safety warnings presented as risk ratios (RR) were estimated by Poisson regression.
Following the 2008 warning for moxifloxacin, the RR of being prescribed moxifloxacin was reduced by 56% (95% CI 0.41-0.47; p < 0.001) for CAP, by 65% (95% CI 0.32-0.39; p < 0.001) for ABS, by 57% (95% CI 0.41-0.45; p < 0.001) for AECB. After the 2012 warning for levofloxacin, the RR of being prescribed levofloxacin was reduced by 31% (95% CI 0.64-0.74; p < 0.001) for CAP, by 14% (95% CI 0.77-0.96; p = 0.007) for ABS, by 27% (95% CI 0.69-0.77; p < 0.001) for AECB. We noticed a prescription-switch to other antibiotics which was not in line with the national guideline recommendations. The warning for moxifloxacin 2009 had no impact on prescribing behaviour.
This study observed an impact on prescribing behaviour in response to regulatory safety warnings for two out of three warnings. Information on therapeutic alternatives should be a part of any safety warning to encourage the intended changes in prescribing behaviour.
This study observed an impact on prescribing behaviour in response to regulatory safety warnings for two out of three warnings. Information on therapeutic alternatives should be a part of any safety warning to encourage the intended changes in prescribing behaviour.
Emergency department visits and hospital admissions are common among nursing home residents (NHRs) and seem to be higher in Germany than in other countries. Yet, research on characteristics of transfers and involved persons in the transfer decision is scarce.
The aim of this study was to analyze the characteristics of hospital transfers from nursing homes (NHs) focused on contacts to physicians, family members and legal guardians prior to a transfer.
We conducted a multi-center study in 14 NHs in the regions Bremen and Lower Saxony (Northwestern Germany) between March 2018 and July 2019. Hospital transfers were documented for 12months by nursing staff using a standardized questionnaire. Data were derived from care records and perspectives of nursing staff and were analyzed descriptively.
Among 802 included NHRs, n = 535 unplanned hospital transfers occurred of which 63.1% resulted in an admission. Main reasons were deterioration of health status (e.g. fever, infections, dyspnea and exsiccosis) (35.1%) and falls/accidents/injuries (33.5%). Within 48h prior to transfer, contact to at least one general practitioner (GP)/specialist/out-of-hour-care physician was 46.2% and varied between the NHs (range 32.3-83.3%). GPs were involved in only 34.8% of transfer decisions. Relatives and legal guardians were more often informed about transfer (62.3% and 66.8%) than involved in the decision (21.8% and 15.1%).
Contacts to physicians and involvement of the GP were low prior to unplanned transfers. The ranges between the NHs may be explained by organizational differences.
Improvements in communication between nursing staff, physicians and others are required to reduce potentially avoidable transfers.
Improvements in communication between nursing staff, physicians and others are required to reduce potentially avoidable transfers.Protein O-GlcNAcylation is a nutrient-related post-translational modification that, since its discovery some 30 years ago, has been associated with the development of neurodegenerative diseases. As reported in Alzheimer's disease (AD), flaws in the cerebral glucose uptake translate into reduced hexosamine biosynthetic pathway flux and subsequently lead to aberrant protein O-GlcNAcylation. Notably, the reduction of O-GlcNAcylated proteins involves also tau and APP, thus promoting their aberrant phosphorylation in AD brain and the onset of AD pathological markers. Down syndrome (DS) individuals are characterized by the early development of AD by the age of 60 and, although the two conditions present the same pathological hallmarks and share the alteration of many molecular mechanisms driving brain degeneration, no evidence has been sought on the implication of O-GlcNAcylation in DS pathology. β-Glycerophosphate Our study aimed to unravel for the first time the role of protein O-GlcNacylation in DS brain alterations positing the attention of potential trisomy-related mechanisms triggering the aberrant regulation of OGT/OGA cycle. We demonstrate the disruption of O-GlcNAcylation homeostasis, as an effect of altered OGT and OGA regulatory mechanism, and confirm the relevance of O-GlcNAcylation in the appearance of AD hallmarks in the brain of a murine model of DS. Furthermore, we provide evidence for the neuroprotective effects of brain-targeted OGA inhibition. Indeed, the rescue of OGA activity was able to restore protein O-GlcNAcylation, and reduce AD-related hallmarks and decreased protein nitration, possibly as effect of induced autophagy.Natalizumab and fingolimod are effective multiple sclerosis (MS) therapies that disrupt lymphocyte migration but have differential effects on B cell maturation and trafficking. We investigated their effects on peripheral blood (PB) and cerebrospinal fluid (CSF) B cell repertoires using next-generation deep sequencing. Paired CSF and PB B cell subsets (naïve, CD27+ memory, and CD27-IgD- double-negative B cells and plasmablasts) were collected by applying flow cytometry at baseline and after 6 months of treatment and their respective heavy-chain variable region repertoires assessed by Illumina MiSeq. Treatment with fingolimod contracted, whereas natalizumab expanded circulating PB B cells. CSF B cell numbers remained stable following fingolimod treatment but decreased with natalizumab therapy. Clonal overlap between CSF and PB B cells was reduced with natalizumab treatment but remained stable with fingolimod therapy. Lineage analyses of pre- and posttreatment CSF B cell repertoires revealed large, clonally expanded B cell clusters in natalizumab-treated MS patients but no intrathecal clonal expansion following fingolimod therapy.