A cyclic analogue, [cyclo(87-99)MBP [87][88][89][90][91][92][93][94][95][96][97][98][99] [87][88][89][90][91][92][93][94][95][96][97][98][99] , reported previously for suppressing, to a varying degree, autoimmune encephalomyelitis in a rat animal model, were found in this study to possess the following immunomodulatory properties: (i) they suppressed the proliferation of a CD4 T-cell line raised from a multiple sclerosis patient, (ii) they scored the best in vitro TH2/TH1 cytokine ratio in peripheral blood mononuclear cell cultures derived from 13 multiple sclerosis patients, inducing IL-10 selectively, and (iii) they bound to HLA-DR4, first to be reported for cyclic MBP peptides. In addition, cyclic peptides were found to be more stable to lysosomal enzymes and Cathepsin B, D, and H, compared to their linear counterparts. Taken together, these data render cyclic mimics as putative drugs for treating multiple sclerosis and potentially other Th1-mediated autoimmune diseases.

BackgroundAntibiotic prescribing rates in care homes are higher than in the general population. Antibiotics disrupt the normal gut flora, sometimes causing antibiotic-associated diarrhoea (AAD).Clostridium difficile(Hall and O’Toole 1935) Prévot 1938 is the most commonly identified cause of AAD. Little is known either about the frequency or type of antibiotics prescribed in care homes or about the incidence and aetiology of AAD in this setting.ObjectivesThe Probiotics for Antibiotic-Associated Diarrhoea (PAAD) study was designed as a two-stage study. PAAD stage 1 aimed to (1) prospectively describe antibiotic prescribing in care homes; (2) determine the incidence ofC. difficilecarriage and AAD (includingC. difficile-associated diarrhoea); and (3) to consider implementation challenges and establish the basis for a sample size estimation for a randomised controlled trial (RCT) of probiotic administration with antibiotics to prevent AAD in care homes. If justified by PAAD stage 1, the RCT would be implemented in PAAD stage 2. However, as a result of new evidence regarding the clinical effectiveness of probiotics on the incidence of AAD, a decision was taken not to proceed with PAAD stage 2.DesignPAAD stage 1 was a prospective observational cohort study in care homes in South Wales with up to 12 months’ follow-up for each resident.SettingRecruited care homes had management and owner’s agreement to participate and three or more staff willing to take responsibility for implementing the study.ParticipantsEleven care homes were recruited, but one withdrew before any residents were recruited. A total of 279 care home residents were recruited to the observational study and 19 withdrew, 16 (84%) because of moving to a non-participating care home.Main outcome measuresThe primary outcomes were the rate of antibiotic prescribing, incidence of AAD, defined as three or more loose stools (type 5–7 on the Bristol Stool Chart) in a 24-hour period, andC. difficilecarriage confirmed on stool culture.ResultsStool samples were obtained at study entry from 81% of participating residents. Over half of the samples contained antibiotic-resistant isolates, with Enterobacteriaceae resistant to ciprofloxacin in 47%. Residents were prescribed an average of 2.16 antibiotic prescriptions per year [95% confidence interval (CI) 1.90 to 2.46]. Antibiotics were less likely to be prescribed to residents from dual-registered homes. The incidence of AAD was 0.57 (95% CI 0.41 to 0.81) episodes per year among those residents who were prescribed antibiotics. AAD was more likely in residents who were prescribed co-amoxiclav than other antibiotics and in those residents who routinely used incontinence pads. AAD was less common in residents from residential homes.ConclusionsCare home residents, particularly in nursing homes, are frequently prescribed antibiotics and often experience AAD. Antibiotic resistance, including ciprofloxacin resistance, is common in Enterobacteriaceae isolated from the stool of care home residents. Co-amoxiclav is associated with greater risk of AAD than other commonly prescribed antibiotics.Trial registrationCurrent Controlled Trials ISRCTN 7954844.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 18, No. 63. See the NIHR Journals Library website for further project information.

Confronting Multiple Sclerosis requires as an underlying step the manipulation of immune response through modification of Myelin Basic Protein peptides. The aim is to design peptidic or nonpeptidic molecules that compete for recognition of self-antigens at the level of antigen presentation. The rational approach is to substitute residues that serve as anchors for the T-Cell Receptor with others that show no binding at all, and those that serve as Major Histocompatibility Complex II anchors with others that present increased binding affinity. The resulting structure, hence, retains normal or increased MHC II binding properties, but fails to activate disease-inducing T-cells. This rational design can only be achieved by identifying the structural requirements for binding of the natural peptide to MHC II, and the anchor residues with their corresponding specific pockets in the binding groove. The peptide-MHC II complex then interacts with the TCR; thus, an additional way to trigger the desired immune response is to alter secondary anchor residues as well as primary ones. In this review, the structural requirements for binding of MBP peptides to MHC II are presented, as are the mechanism and key features for TCR recognition of the peptide-MHC II complex.

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Reflective practice strategies can enable healthcare practitioners to draw on previous experiences to render more effective judgment in clinical situations. The central argument presented in this commentary is that education programs and structures for continuing professional development (CPD) and revalidation of professionals sharpen their focus regarding self-assessment to identify gaps in skills and attitudes rather than merely as a means of on-going monitoring. Pharmacy undergraduate and professional education need to promote reflective practice strategies that foster self-evaluation to promote pharmacists' readiness for practice change and advance patient care within rapidly expanding roles and scope of practice.

This novel and innovative approach supports novice reflectors, encourages reflection on action and enhances professional development. It is a structured yet flexible tool, for which there was a gap in the published literature. It can be utilized in varied placements in pharmacy curricula internationally.

ObjectiveA National Health Service (NHS)-funded sore throat test and treat (STTT) service was introduced in selected pharmacies in two local health boards in Wales, as an extension to the national pharmacy common ailment scheme. The aim of this study was to evaluate the impact of STTT on provision and quality of patient care, namely antibiotic use, patient safety and general practitioner (GP) consultation rates.MethodsSecondary analyses of STTT consultation data to describe service outcomes, and routine data to explore changes in antibiotic prescribing and the prevalence of complications. Data were also collected from one GP practice to explore the feasibility of measuring changes in sore throat consultation rates in general practice.ResultsLess than 20% of 1725 consultations resulted in antibiotic supply. The availability of STTT was associated with greater reductions in prescriptions for phenoxymethylpenicillin than in areas where STTT was not available (−3.8% and −3.4%, difference 0.4%). When pharmacy supplies were included, the reductions in the supply of the antibiotic were similar. No increase in the monthly number of incidents of quinsy was detected, and patients were appropriately referred to other healthcare professionals during pharmacy consultations. GP consultation rates since introduction of STTT were found to be lower than the equivalent monthly average since 2014.ConclusionsData from the first 5 months of the STTT service suggest that it may have a role in safely rebalancing uncomplicated sore throat management from general practice to community pharmacies while continuing to promote antibiotic stewardship.

Background There is a lack of evidence on how the multimodal dynamic process of resilience has impacted personal adaptation of frontline healthcare professionals, working under extreme pressure during the COVID-19 global pandemic. Objectives To explore resilience, burnout and wellbeing for UK pharmacists in patient-facing roles, including individual and organisational factors that align to the ABC-X theoretical model of the dynamic process of resilience. Methods A non-experimental pragmatist research design was adopted, with a cross-sectional online survey distributed via social media and professional networks between June and July 2020. Quantitative data aligned to a positivist research paradigm was collected using validated scores, to statistically analyse wellbeing, burnout and resilience. Qualitative textual data, consistent with an interpretivist research paradigm, were analysed following an inductive thematic approach. Results A total of 199 surveys from pharmacists working within community, hospital and GP sectors were analysed. Wellbeing scores were strongly correlated to resilience scores. Wellbeing and resilience scores were both inversely correlated with burnout scores. Two-thirds of participants were classified as high-risk within the burnout scales. Key stressors were highlighted by participants, who described how individual resources and perceptions shaped their experience, which overall contributed to their burnout. Organisations that supported pharmacists embraced change and quickly adopted new ways of working, such as teleconsultations, flexible and remote working, redesign of workflow, alongside clear guidance. However, there was also reported frustration at lack of, slow or conflicting guidance from employers. Conclusions This study adds to the growing evidence base for how individuals are affected by adverse events in a dynamic environment, alongside the role that employers can play in supporting individual and organisational resilience. It provides an opportunity to learn from pharmacists' responses to the COVID-19 pandemic, and a call to action for healthcare organisations to rebuild and invest resources into sustained support for staff wellbeing.