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Background: Spinocerebellar ataxia type 4 (SCA4) is an autosomal dominant ataxia with invariable sensory neuropathy originally described in a family with Swedish ancestry residing in Utah more than 25 years ago. Despite tight linkage to the 16q22 region, the molecular diagnosis has since remained elusive. Objectives: Inspired by pathogenic structural variation implicated in other 16q‐ataxias with linkage to the same locus, we revisited the index SCA4 cases from the Utah family using novel technologies to investigate structural variation within the candidate region. Methods: We adopted a targeted long‐read sequencing approach with adaptive sampling on the Oxford Nanopore Technologies (ONT) platform that enables the detection of segregating structural variants within a genomic region without a priori assumptions about any variant features. Results: Using this approach, we found a heterozygous (GGC)n repeat expansion in the last coding exon of the zinc finger homeobox 3 (ZFHX3) gene that segregates with disease, ranging between 48 and 57 GGC repeats in affected probands. This finding was replicated in a separate family with SCA4. Furthermore, the estimation of this GGC repeat size in short‐read whole genome sequencing (WGS) data of 21,836 individuals recruited to the 100,000 Genomes Project in the UK and our in‐house dataset of 11,258 exomes did not reveal any pathogenic repeats, indicating that the variant is ultrarare. Conclusions: These findings support the utility of adaptive long‐read sequencing as a powerful tool to decipher causative structural variation in unsolved cases of inherited neurological disease. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Introduction: Evidence suggests that, while a preference for functional Health Literacy (HL) outcome measurement exists, researchers are converging towards more all‐encompassing instruments. While this claim is present in the HL field, minimal research has comprehensively explored the state of community HL measurement practices at the direct and proxy level. The almost exclusive focus on direct, as opposed to proxy, community HL measurement indicates a review of progress is needed. Objective: To identify HL outcome measurement practices for community HL interventions at the direct and proxy level of measurement. Search Strategy: Medline, PsycINFO, Web of Science, ERIC, Embase, Scopus, CINAHL, ProQuest Dissertations and Theses, Google Scholar and targeted websites were searched. Inclusion Criteria: Studies were sampled from the general population, included HL as an outcome of interest, involved an intervention aiming to improve HL, were English‐text publications and were published ≥2010. Data Extraction and Synthesis: Study author(s) and publication years, sample characteristics, intervention profiles and direct and proxy instrument and outcome measurement information were extracted. Full‐text review retrieved 25 eligible studies. Main Results: In total, 21 unique direct and 38 unique proxy instruments were extracted. The majority of interventions assessed functional compared to communicative, critical, and other HL domains, with objective instruments more frequently used than subjective or combined objective‐subjective types, though more unique subjective HL instruments were extracted overall. The Test of Functional HL in Adults was the most popular instrument, and perceived health, knowledge, behaviors and health intentions were the most frequent proxy outcome measures, with only the Healthy Lifestyle Behavior Scale‐II and Patient Activation Measure used across multiple interventions. Discussion and Conclusions: Direct HL outcome practices endured a unidimensional profile, despite previous suggestions of a convergence towards holistic instruments. This review provides the first overview of proxy HL measurement across community HL interventions, identifying substantial variation in proxy outcome practices. Patient or Public Contribution: A University‐based senior librarian contributed to the development of the search strategy, and reviewed iterations of the strategy until refinement was complete. No further public or patient contribution was made given the review‐based nature of the research. [ABSTRACT FROM AUTHOR]

The CRF01_AE and CRF07_BC clades dominate the human immunodeficiency virus (HIV) epidemics in China. Both clades have been identified in the men who have sex with men (MSM) population in Guangdong province, raising a serious concern of possible complex recombination events ahead. Here, we report the first case of CRF01_AE/CRF07_BC recombinant sampled from a MSM patient in southern China. The genomic structure of this case is a mosaic with some regions resembling the CRF01_AE and CRF07_BC clades. Our phylogenetic analyses show that the two parental lineages of this recombinant virus were mainly found in the MSM population. This case has a different genomic composition compared with other recombinants descended from the same parental clades CRF01_AE and CRF07_BC. Our finding suggests that the MSM populations have become a hotspot for expanding viral diversity through the viral recombination mechanism. Therefore, further epidemiologic surveillance and monitoring should be conducted within the MSM populations to help advance our knowledge of viral transmission mechanisms. Additionally, these measures will serve to enhance the control and prevention of HIV/acquired immunodeficiency syndrome in China. [ABSTRACT FROM AUTHOR]

This paper challenges the western concept of graduate employability as a measure of student success through a case study of a collaboration between pharmacy colleagues in universities in Nairobi, Kenya and Nottingham, UK. As Pharmacy programmes globally adapt their courses to a competency‐based education (CBE) approach, we outline the implications of this for graduate success in Kenya. The Ministry of Education in Kenya recently announced a move to CBE across all educational sectors. This has led to a reconfiguring of how pharmacy is not only taught, but also assessed, and what success means for pharmacy graduates in Kenya. The collaboration has highlighted the need for key stakeholders to work together and influence policy change, and redefine employability in terms of behaviours that meet country‐wide needs. We outline some of the processes and collaborations we formed to redevelop pharmacy programmes in Kenya, and suggest recommendations for continuing partnerships and sustainability. [ABSTRACT FROM AUTHOR]

Rationale, Aims, and Objectives Pharmaceutical care involves patient-centred pharmacist activity to improve medicines management by patients. The implementation of this service in a comprehensive manner, however, requires considerable organisation and effort, and indeed, it is often not fully implemented in care settings. The main objective was to assess how pharmaceutical care provision within community pharmacy has evolved over time in Europe. Method A cross-sectional questionnaire-based survey of community pharmacies, using a modified version of the Behavioural Pharmaceutical Care Scale (BPCS) was conducted in late 2012/early 2013 within 16 European countries and compared with an earlier assessment conducted in 2006. Results The provision of comprehensive pharmaceutical care has slightly improved in all European countries that participated in both editions of this survey (n = 8) with progress being made particularly in Denmark and Switzerland. Moreover, there was a wider country uptake, indicating spread of the concept. However, due to a number of limitations, the results should be interpreted with caution. Using combined data from participating countries, the provision of pharmaceutical care was positively correlated with the participation of the community pharmacists in patient-centred activities, routine use of pharmacy software with access to clinical data, participation in multidisciplinary team meetings, and having specialized education. Conclusions The present study demonstrated a slight evolution in self-reported provision of pharmaceutical care by community pharmacists across Europe, as measured by the BPCS. The slow progress suggests a range of barriers, which are preventing pharmacists moving beyond traditional roles. Support from professional bodies and more patient-centred community pharmacy contracts, including remuneration for pharmaceutical care services, are likely to be required if quicker progress is to be made in the future. [ABSTRACT FROM AUTHOR]

The most economically important diseases of grapevine cultivation worldwide are caused by the fungal pathogen powdery mildew ( Erysiphe necator syn. Uncinula necator) and the oomycete pathogen downy mildew ( Plasmopara viticola). Currently, grapegrowers rely heavily on the use of agrochemicals to minimize the potentially devastating impact of these pathogens on grape yield and quality. The wild North American grapevine species Muscadinia rotundifolia was recognized as early as 1889 to be resistant to both powdery and downy mildew. We have now mapped resistance to these two mildew pathogens in M. rotundifolia to a single locus on chromosome 12 that contains a family of seven TIR- NB- LRR genes. We further demonstrate that two highly homologous (86% amino acid identity) members of this gene family confer strong resistance to these unrelated pathogens following genetic transformation into susceptible Vitis vinifera winegrape cultivars. These two genes, designated resistance to U ncinula necator ( Mr RUN1) and resistance to P lasmopara viticola ( Mr RPV1) are the first resistance genes to be cloned from a grapevine species. Both Mr RUN1 and Mr RPV1 were found to confer resistance to multiple powdery and downy mildew isolates from France, North America and Australia; however, a single powdery mildew isolate collected from the south-eastern region of North America, to which M. rotundifolia is native, was capable of breaking Mr RUN1-mediated resistance. Comparisons of gene organization and coding sequences between M. rotundifolia and the cultivated grapevine V. vinifera at the Mr RUN1/ Mr RPV1 locus revealed a high level of synteny, suggesting that the TIR- NB- LRR genes at this locus share a common ancestor. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study, which was part of the first independent evaluation of patient reporting of adverse drug reactions (ADRs) to the Yellow Card Scheme, was to observe the three reporting systems (paper, internet and telephone) 'in use' in a simulated setting to identify aspects which facilitated or hindered reporting. Methods Forty adult participants were recruited from the general public using posters in pharmacies and a press article, and from a pool of volunteer simulated patients maintained by University of Nottingham medical and pharmacy schools. The participants, in seven groups that met at different times, were asked to 'think aloud,' as they were individually observed completing the reporting process for the paper and internet system, highlighting their thoughts and any issues encountered. They were asked to talk about their experience of reporting immediately after they had reported by telephone. Data from the field notes were analysed thematically and supplemented with relevant information from digital audio recordings. Conclusions Usability testing using the 'think aloud' approach worked well and identified areas of the Yellow Card reporting system which could be improved. Whilst the three methods of reporting available to the public are all reasonably 'fit for purpose', there were many suggestions identified for improving ease of completion and data quality, especially for the internet system. When systems for reporting of ADRs are designed, they should be tested by potential users before they are launched, so that potential problems are identified in advance. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Little is known about why patients actually report suspected adverse drug reactions to schemes like the Yellow Card Scheme. Greater understanding of the reasons for reporting could be of benefit in marketing strategies aiming to increase the number of reports. WHAT THIS STUDY ADDS • Direct patient reporting through the Yellow Card Scheme is viewed as important by those who have used the scheme, in order to provide the patient experience for the benefit of pharmacovigilance, as an independent perspective from those of health professionals. • Reporters viewed the Yellow Card Scheme as an important opportunity to describe their experiences for the benefit of others and to contribute to pharmacovigilance. • The Yellow Card Scheme's independence from health professionals was regarded as important, in part to provide the patient perspective to manufacturers and regulators, but also because of dismissive attitudes and under-reporting by health professionals. AIM To explore the opinions of patient reporters to the UK Yellow Card Scheme (YCS) on the importance of the scheme. METHODS Postal questionnaires were distributed on our behalf to all patient reporters submitting a Yellow Card to the Medicines and Healthcare Regulatory Agency (MHRA) between March and December 2008, with one follow-up reminder to non-responders. Qualitative analysis was undertaken of responses to an open question asking why respondents felt patient reporting was important. This was followed up by telephone interviews with a purposive sample of selected respondents. RESULTS There were 1362 evaluable questionnaires returned from 2008 distributed (68%) and 1238 (91%) respondents provided a total of 1802 comments. Twenty-seven interviews were conducted, which supported and expanded the views expressed in the questionnaire. Four main themes emerged, indicating views that the YCS was of importance to pharmacovigilance in general, manufacturers and licensing authorities, patients and the public and health professionals. Reporters viewed the YCS as an important opportunity to describe their experiences for the benefit of others and to contribute to pharmacovigilance. The scheme's independence from health professionals was regarded as important, in part to provide the patient perspective to manufacturers and regulators, but also because of dismissive attitudes and under-reporting by health professionals. CONCLUSION Direct patient reporting through the YCS is viewed as important by those who have used the scheme, in order to provide the patient experience for the benefit of pharmacovigilance, as an independent perspective from those of health professionals. [ABSTRACT FROM AUTHOR]

Fever-induced refractory epileptic encephalopathy in school-age children (FIRES) is a clinically recognized epileptic encephalopathy of unknown aetiology. Presentation in previously healthy children is characterized by febrile status epilepticus. A pharmacoresistant epilepsy ensues, occurring in parallel with dramatic cognitive decline and behavioural difficulties. We describe a case of FIRES in a 4-year-old boy that was associated with elevated voltage-gated potassium channel (VGKC) complex antibodies and a significant clinical and immunological response to immunomodulation. This case, therefore, potentially expands the clinical phenotype of VGKC antibody-associated disease to include that of FIRES. Prior to immunomodulation, neuropsychology assessment highlighted significant attention, memory, and word-finding difficulties. The UK version of the Wechsler Preschool and Primary Scale of Intelligence assessment indicated particular difficulties with verbal skills (9th centile). Immunomodulation was initially administered as intravenous methylprednisolone (followed by maintenance oral prednisolone) and later in the disease course as regular monthly intravenous immunoglobulin infusions and low-dose azathioprine. Now aged 6 years, the seizure burden in this child is much reduced, although increased seizure frequency is observed in the few days before his monthly immunoglobulin infusions. Formal IQ assessment has not been repeated but there is no clinical suggestion of further cognitive regression. VGKC complex antibodies have been reported in a range of central and peripheral neurological disorders (predominantly presenting in adulthood), and the identification of elevated VGKC complex antibodies, combined with the response to immunotherapies in this child, supports an autoimmune pathogenesis in FIRES with potential diagnostic and therapeutic implications. [ABSTRACT FROM AUTHOR]

The article presents a study on the views and experiences of patients who make drug reaction reports to the Yellow Card Scheme (YCS) in Great Britain. The Medicines and Healthcare products Regulatory Agency (MHRA) developed a questionnaire to get the responses of patients who report suspected adverse drug reactions (ADRs) through the YCS from March 2008 to January 2009. It has been found out that most of the patients find it easy to use the system of reporting suspected ADRs and that they will recommend it to others.

To systematically review feedback from pharmacy users on their perceptions and experiences of health-related advice and services provided from community pharmacies. The focus of the review was community pharmacy activities in relation to promoting health and well-being, preventing ill-health and maintaining health. Searches were conducted for peer-reviewed (international) and non-peer-reviewed (UK) research. Electronic databases searched included MEDLINE, EMBASE, Cochrane Library and International Pharmaceutical Abstracts; hand searches of key journals and conference abstracts, key informants. Key informants in the UK were contacted to identify unpublished studies. The inclusion period was 1990 onwards. Data were abstracted into a matrix by one author with a sample checked by a second. The Health Development Agency's Evidence Base 2000 standards and the evidence categories used by the Department of Health in the National Service Frameworks were applied to each item. Seven peer reviewed papers and 13 non-peer reviewed reports were identified for inclusion in the review. Consumer usage of pharmacies is almost universal with prescription supplies and purchase of over the counter medicines predominating. Evidence shows that not only is usage low for general health advice, but that pharmacists are perceived as ‘drugs experts’ rather than experts on health and illness. Emergency hormonal contraception and head lice management schemes have been well received. There is a need to consider privacy and confidentiality surrounding advice giving. Users of community pharmacy-based health development initiatives express a high level of satisfaction. If community pharmacies are to be used to their full extent, then actions to extending the public's awareness and acceptance of the pharmacist's role in giving advice will be crucial. Further research will be needed to measure any change in premises development on the public's perception of the level of privacy in pharmacies. [ABSTRACT FROM AUTHOR]