Immune complex-mediated co-ligation of the BCR with FcγRIIB results in homeostatic apoptosis of B cells involving Fas signalling that is defective in the MRL/Lpr model of systemic lupus erythematosus

Negative regulation of B cell activation by cognate immune complexes plays an important homeostatic role in suppressing B cell hyperactivity and preventing consequent autoimmunity. Immune complexes co-ligate the BCR and FcγRIIB resulting in both growth arrest and apoptosis. We now show that such apoptotic signalling involves induction and activation of p53 and its target genes, the pro-apoptotic Bcl-2 family members, Bad and Bid, as well as nuclear export of p53. Collectively, these events result in destabilisation of the mitochondrial and lysosomal compartments with consequent activation and interplay of executioner caspases and endosomal-derived proteases. In addition, the upregulation of Fas and FasL with consequent activation of caspase 8-dependent death receptor signalling is required to facilitate efficient apoptosis of B cells. Consistent with this role for Fas death receptor signalling, apoptosis resulting from co-ligation of the BCR and FcγRIIB is defective in B cells from Fas-deficient MRL/MpJ-Faslpr mice. As these mice develop spontaneous, immune complex-driven lupus-like glomerulonephritis, targeting this FcγRIIB-mediated apoptotic pathway may therefore have novel therapeutic implications for systemic autoimmune disease

Ambon Ahoy!

tag=1 data=Ambon Ahoy! tag=2 data=Gauld, Natalie tag=3 data=Territory Business, tag=6 data=Third Quarter 1994 tag=7 data=15. tag=8 data=SHIPPING%SPORT tag=9 data=AMBON YACHT RACE tag=13 data=IN

Double-Dosing and Other Dangers with Non-Prescription Medicines: Pharmacists’ Views and Experiences

The aim of this paper was to explore pharmacists’ views on reclassifications from pharmacy-only to general sales and their experiences with the supply of these medicines, in addition to pharmacists’ views on the reclassification of the shingles vaccine and sildenafil to be available through ‘accredited’ pharmacists. New Zealand community pharmacists were surveyed in 2013 with a written questionnaire of six Likert-style or open-ended questions sent to Pharmacy Guild member pharmacies. The analysis involved descriptive statistics. Responses were received from 246 pharmacies. Two thirds of pharmacists supported the reclassification of the shingles vaccine and sildenafil, although 14% disagreed with the sildenafil reclassification. Over 90% of pharmacists disagreed with the reclassification of paracetamol and ibuprofen liquids, omeprazole, naproxen, and oxymetazoline from pharmacy-only medicine to general sales. This opinion was strongest for omeprazole. With liquid paracetamol and ibuprofen, pharmacists described consumer confusion with dosing, and particularly potentially doubling-up on liquid analgesics/antipyretics including using both prescription and non-prescription variants. Many reported giving safety advice frequently. Anti-inflammatories and omeprazole were also subject to potential double-dosing, as well as requests by consumers with contraindications, precautions, and drug interactions, and for inappropriate indications. Pharmacists described various interventions, including some that were potentially life-saving. Pharmacy availability of medicines provides the potential for intervention that would not happen in a general sales environment

A new model of prescription to nonprescription reclassification: the calcipotriol case study

Background: Medicines reclassification from prescription to nonprescription (switch) has slowed in some countries, including the United States. New thinking may be necessary to drive this area, including third-party reclassification and better use of the pharmacist, collaborative care, or innovative technologies. Objective: The goal of this study was to describe a recent, successful, third-party reclassification of topical calcipotriol, a treatment for psoriasis, including the process, challenges, and solutions. Methods: This case study used multiple sources of information, including an application to the Medicines Classification Committee (MCC) in New Zealand, the response letter from the MCC, published minutes of the relevant MCC meeting, and interview data. A heuristic qualitative approach was used that embraces the involvement and experiences of the lead researcher. Results: The third-party reclassification of topical calcipotriol generated challenges, mainly due to initial manufacturer opposition. The greatest hurdle was an inability to change the label. However, requiring mandatory pharmacist consultation, with supply under specified conditions, overcame the barriers. Such conditions included supply only to adults with mild to moderate psoriasis, limits on weekly usage and pack size supplied, and the use of a collaborative care approach requiring previous physician diagnosis and advising the physician of usage. An algorithm for supply was developed. The flexibility of the MCC, an advisory committee, and the medicines regulator, both in considering a third-party approach and in allowing an exemption to prescription supply under specific conditions, was vital to the success of the reclassification. Conclusions: Third-party reclassification may be possible in some countries, particularly where supply can be limited to pharmacists only. A flexible approach may be needed from the committee and regulator to assist such reclassification. Given the multiple beneficiaries of reclassification, removing reliance on the pharmaceutical companies to drive reclassification and/or using new models of supply may provide impetus to the reclassification arena

Why are self-medication opportunities limited in Austria? An interview study and comparison with other countries.

BackgroundAustria has high health resource use compared to similar countries. Reclassifying (switching) medicines from prescription to non-prescription can reduce pressure on health resources and aid timely access to medicines. Since Austria is less progressive in this area than many other countries, this research aimed to elucidate enablers and barriers to it reclassifying medicines and make recommendations for change in the context of similar research conducted elsewhere.MethodsQualitative research using a heuristic approach was conducted in Austria in 2018. Informed by their own "insider" and "outsider" knowledge, the authors identified themes from personal interviews with 24 participants, including reclassification committee members, government officials and stakeholders, before comparing these themes with earlier research findings.ResultsSignificant barriers to reclassification included committee conservatism, minimal political support, medical negativity and few company applications. Insufficient transparency about committee decisions, expectations of adverse committee decisions and a limited market discouraged company applications. Austria's 'social partnership' arrangement and consensus decision making aided a conservative approach, but the regulator and an alternative non-committee switch process were enabling. Pharmacy showed mixed interest in reclassification. Suggested improvements include increasing transparency, committee composition changes, encouraging a more evidence-based approach by the committee, more pharmacy undergraduate clinical training, and companies using scientific advisory meetings and submitting high quality applications.ConclusionRemoving barriers to reclassification would facilitate non-prescription availability of medicines and encourage self-care, and could reduce pressure on healthcare resources

Influences on Pregnant Women’s and Health Care Professionals’ Behaviour Regarding Maternal Vaccinations: A Qualitative Interview Study

The uptake of maternal influenza and pertussis vaccinations is often suboptimal. This study explores the factors influencing pregnant women’s and health care professionals’ (HCPs) behaviour regarding maternal vaccinations (MVs). Pregnant/recently pregnant women, midwives, pharmacists and general practice staff in Waikato, New Zealand, were interviewed. The analysis used the behaviour change wheel model. Interviews of 18 women and 35 HCPs revealed knowledge about MVs varied with knowledge deficiencies hindering the uptake, particularly for influenza vaccination. HCPs, especially midwives, were key in raising women’s awareness of MVs. Experience with vaccinating, hospital work (for midwives) and training increased HCPs’ knowledge and proactivity about MVs. A “woman’s choice” philosophy saw midwives typically encouraging women to seek information and make their own decision. Women’s decisions were generally based on knowledge, beliefs, HCPs’ emphasis and their perceived risk, with little apparent influence from friends, family, or online or promotional material. General practice’s concentration on children’s vaccination and minimal antenatal contact limited proactivity with MVs. Busyness and prioritisation appeared to affect HCPs’ proactivity. Multi-pronged interventions targeting HCPs and pregnant women and increasing MV access are needed. All HCPs seeing pregnant women should be well-informed about MVs, including how to identify and address women’s questions or concerns about MVs to optimise uptake

Barriers in Australia and New Zealand for switches (based on interview data).

<p>Barriers in Australia and New Zealand for switches (based on interview data).</p

Key reasons for Trans-Tasman variation.

<p>Key reasons for Trans-Tasman variation.</p

Usual lines of inquiry.

<p>Usual lines of inquiry.</p

Outcomes of ‘progressive’ switches considered in New Zealand in 2000–2011.

<p>Source: Medicines Classification Meeting minutes. Medicines were counted once per period, regardless of the numbers of considerations for each medicine. The Medicines Classification Committee had three members change in 2004.</p