Scoping of pharmacists' health leadership training needs for effective antimicrobial stewardship in Africa.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern currently mitigated by antimicrobial stewardship (AMS). Pharmacists are strategically placed to lead AMS actions that contribute to responsible use of antimicrobials; however, this is undermined by an acknowledged health leadership skills deficit. Learning from the UK's Chief Pharmaceutical Officer's Global Health (ChPOGH) Fellowship programme, the Commonwealth Pharmacists Association (CPA) is focused to develop a health leadership training program for pharmacists in eight sub-Saharan African countries. This study thus explores need-based leadership training needs for pharmacists to provide effective AMS and inform the CPA's development of a focused leadership training programme, the 'Commonwealth Partnerships in AMS, Health Leadership Programme' (CwPAMS/LP). METHODS: A mixed methods approach was undertaken. Quantitative data were collected via a survey across 8 sub-Saharan African countries and descriptively analysed. Qualitative data were collected through 5 virtual focus group discussions, held between February and July 2021, involving stakeholder pharmacists from different sectors in the 8 countries and were analysed thematically. Data were triangulated to determine priority areas for the training programme. RESULTS: The quantitative phase produced 484 survey responses. Focus groups had 40 participants from the 8 countries. Data analysis revealed a clear need for a health leadership programme, with 61% of respondents finding previous leadership training programmes highly beneficial or beneficial. A proportion of survey participants (37%) and the focus groups highlighted poor access to leadership training opportunities in their countries. Clinical pharmacy (34%) and health leadership (31%) were ranked as the two highest priority areas for further training of pharmacists. Within these priority areas, strategic thinking (65%), clinical knowledge (57%), coaching and mentoring (51%), and project management (58%) were selected as the most important. CONCLUSIONS: The study highlights the training needs of pharmacists and priority focus areas for health leadership to advance AMS within the African context. Context-specific identification of priority areas supports a needs-based approach to programme development, maximising African pharmacists' contribution to AMS for improved and sustainable patient outcomes. This study recommends incorporating conflict management, behaviour change techniques, and advocacy, amongst others, as areas of focus to train pharmacist leaders to contribute to AMS effectively.

Characteristics and outcome of patients transported by police to emergency departments under section 351 of the Mental Health Act 2014 (Vic).

OBJECTIVE: To determine characteristics, precipitating circumstances, clinical care, outcome and disposition of patients brought to the ED under section 351 (s351, police detention and transport) powers of the Mental Health Act 2014 (Vic) (MHAV). METHODS: This is an observational cohort study conducted in two metropolitan teaching hospitals in Victoria. Participants were adult patients brought to ED under s351 of the MHAV. Data collected included demographics, event circumstances, pre-hospital and ED interventions and outcome. Analyses are descriptive. RESULTS: The present study included 438 patient encounters. Median age was 34 years. In 84% of encounters (368/438) patients were co-transported with ambulance. The most common primary reason for detainment was suicide risk/intent (296/438, 67.6%) followed by abnormal behaviour without threat to self or others (92/438, 21%). In ED, parenteral sedation was administered in 11% (48/438). Physical restraint was applied in 17.6% (77/438). Psychiatric admission was required in 23.5% (103/438). In 63 cases, psychiatric admission was involuntary (14.4%). Most patients (297/438, 67.8%) were discharged home. A subset of patients had recurrent s351 presentations. Eighteen (5.6%) patients accounted for 22% (96/438) of all events. CONCLUSION: Most patients brought to ED under s351 of the MHAV had expressed intention to self-harm, did not require medical intervention and were discharged home. It could be questioned whether the current application of s351 is consistent with the least restrictive principles of the MHAV, especially as there is no apparent monitoring or reporting of the use of these powers. There were a concerning number of patients with multiple s351 events over a short period.

Outcomes of a National, Cross-Sector Antimicrobial Stewardship Training Initiative for Pharmacists in England.

(1) Background: Pharmacists play a pivotal role in tackling Antimicrobial resistance through antimicrobial stewardship (AMS) and are well placed to lead behaviour change interventions across the healthcare system; (2) Methods: A cross-sector AMS training initiative for pharmacists was implemented across England, with three cohorts between 2019-2021. Each cohort took part in an introductory workshop, followed- by a workplace-based quality improvement project supported by peer-assisted learning sessions. Completion of training was determined by an end of training assessment after three to four months. Outcome data and learner survey results were collated, anonymised, and analysed by the training provider. (3) Results: In total, 118 pharmacists participated in the introductory workshop, 70% of these subsequently undertook an improvement project, and 48% engaged workplace stakeholders in the process. Interventions were designed by 57% of learners and 18% completed a at least one Plan-Do-Study-Act cycle. Approximately a quarter of learners met the requirements for a Certificate of Completion. Knowledge quiz scores were obtained from 115 learners pre-training and 28 learners post-training. Paired t-tests conducted for 28 learners showed a statistically significant improvement in mean score from 67.7% to 81.1% (p < 0.0001). Sixty-two learner survey responses were received during the training and 21 follow-up survey responses 6 to 12 months post training. Of the 21 responses to the follow-up survey, ongoing quality improvement work and improvement outcomes were reported by nine and six learners, respectively. (4) Conclusions: The delivery of workplace-based training at scale can be challenging, however this study demonstrates that coupling learning with workplace implementation and peer support can promote behaviour change in learners. Further study into the impact of providing pharmacists across sectors and geographies with access to this type of training will help inform ongoing workforce development interventions.

Sleep Pathology in Creutzfeldt-Jakob Disease.

STUDY OBJECTIVES: Associations between sleep and neurodegenerative diseases have become increasingly evident. This study aims to characterize the prevalence and type of sleep pathology in Creutzfeldt-Jakob disease (CJD), a rapidly progressive, fatal neurodegenerative disease. METHODS: In this observational cross-sectional cohort study, we performed a retrospective analysis of sleep signs and symptoms in a consecutive group of patients with definite CJD at a tertiary care medical center (n = 28). Polysomnography was performed in 14 patients. RESULTS: Although only 5 of 28 patients carried a premorbid sleep diagnosis, signs/symptoms of sleep pathology were present in 25 patients. Eleven reported hypersomnia whereas 13 reported insomnia. Seven had restless legs symptoms and/or periodic limb movements of sleep, and nine reported parasomnias. Of the 14 patients who underwent polysomnography, 1 did not show sleep, 9 (69%) had poorly formed or absent sleep spindles and/or K-complexes, and 10 (77%) had sleep-disordered breathing. Of the 8 patients who experienced rapid eye movement (REM) sleep during the polysomnography, 3 (38%) showed REM sleep without atonia, and 2 patients met criteria for REM sleep behavior disorder. Median total sleep time was 226 (interquartile range [IQR] = 195-282) min. Median sleep efficiency was 58.5% (IQR = 41-65.5 %). Median REM time was 0.35% (IQR = 0-7.125%). Five patients (38%) demonstrated periodic limb movements during polysomnography. One case is presented. CONCLUSIONS: Sleep pathology is common in CJD, and screening for sleep pathology is indicated in the evaluation of patients with rapidly progressive dementias. Early identification and treatment of sleep pathology may provide an intervenable target for CJD.

Sibling Experiences: Living with Young Persons with Autism Spectrum Disorders.

Like other young people, those with autism spectrum disorder (ASD) have an impact on siblings in both positive and negative ways. Research indicates positive attributes include maturity and responsibility; positive self-concept; less quarrelling and competition; admiration for the person with ASD; and satisfactory sibling relationships. Negative attributes include fear of frightening or violent behavior, decreased sibling intimacy, and social and emotional difficulties. However, most research relies on information from parents/teachers, rather than from siblings. Therefore, this qualitative descriptive study explored experiences of 11 brothers and 11 sisters living with a young person with ASD through audiorecorded semi-structured interviews. Analysis revealed the overall theme was contradiction. Participants recognized difficulties (decreased parental attention, extra responsibility, bothersome behaviors, communication difficulties) and positive aspects (became empathetic, loved and appreciated the child, realized the experience was life-changing) of living with a young person with ASD. Younger siblings frequently reflected on childhood experiences, wished they could play together, and mentioned what the young person could do. Adolescent siblings learned life lessons from the experience, talked about life changes when ASD was diagnosed, and seemed introspective and protective toward the young person with ASD. Male siblings often wished they played more often while growing up with the young person, and frequently mentioned the child/adolescent's aggressive behaviors; female siblings focused on relationship and communication difficulties of the young person ASD. Interventions to help siblings provide positive behavioral support, engage in developmentally appropriate play, and communicate reciprocally are warranted. Nurses can help parents understand siblings' perceptions and can encourage parents to support siblings.

Role of magnetic resonance imaging, cerebrospinal fluid, and electroencephalogram in diagnosis of sporadic Creutzfeldt-Jakob disease.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive dementia (RPD) that can be difficult to identify antemortem, with definitive diagnosis requiring tissue confirmation. We describe the clinical, magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), and electroencephalogram (EEG) measures of a small cohort of 30 patients evaluated for RPD. Clinical and diagnostic measures were cross-sectionally obtained from 17 sCJD patients (15 definite, two probable), 13 non-prion rapidly progressive dementia patients (npRPD), and 18 unimpaired controls. In a subset of patients (nine sCJD and nine npRPD) diffusion tensor imaging (DTI) measures [fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)] were also obtained for the caudate, corpus callosum, posterior limb of the internal capsule, pulvinar, precuneus, and frontal lobe. Differences among groups were assessed by an analysis of variance. Compared to npRPD individuals, sCJD patients had cerebellar dysfunction, significantly higher CSF tau, "positive" CSF 14-3-3, and hyperintensities on diffusion-weighted imaging (DWI) that met previously established imaging criteria for sCJD. EEG changes were similar for the two groups. In addition, sCJD patients had significant decreases in DTI measures (MD, AD, RD but not FA) within the caudate and pulvinar compared to either npRPD patients or unimpaired controls. Our results confirm that CSF abnormalities and MRI (especially DWI) can assist in distinguishing sCJD patients from npRPD patients. Future longitudinal studies using multiple measures (including CSF and MRI) are needed for evaluating pathological changes seen in sCJD patients.

Direct targeting of alphavbeta3 integrin on tumor cells with a monoclonal antibody, Abegrin.

The humanized monoclonal antibody Abegrin, currently in phase II trials for treatment of solid tumors, specifically recognizes the integrin alphavbeta3. Due to its high expression on mature osteoclasts, angiogenic endothelial cells, and tumor cells, integrin alphavbeta3 functions in several pathologic processes important to tumor growth and metastasis. Targeting of this integrin with Abegrin results in antitumor, antiangiogenic, and antiosteolytic activities. Here, we exploit the species specificity of Abegrin to evaluate the effects of direct targeting of tumor cells (independent of targeting of endothelia or osteoclasts). Flow cytometry analysis of human tumor cell lines shows high levels of alphavbeta3 on many solid tumors, including cancers of the prostate, skin, ovary, kidney, lung, and breast. We also show that tumor growth of alphavbeta3-expressing tumor cells is inhibited by Abegrin in a dose-dependent manner. We present a novel finding that high-dose administration can actively impair the antitumor activity of Abegrin. We also provide evidence that antibody-dependent cellular cytotoxicity contributes to in vitro and in vivo antitumor activity. Finally, it was observed that peak biological activity of Abegrin arises at serum levels that are consistent with those achieved in clinical trials. These results support a concept that Abegrin can be used to achieve selective targeting of the many tumor cells that express alphavbeta3 integrin. In combination with the well-established concept that alphavbeta3 plays a key role in cancer-associated angiogenesis and osteolytic activities, this triad of activity could provide new opportunities for therapeutic targeting of cancer.

Neurofibromatosis 1: from lab bench to clinic.

Neurofibromatosis type 1 is a common autosomal dominant disorder in which affected children and adults develop both benign and malignant tumors. In addition to tumor formation, children with neurofibromatosis type 1 may exhibit specific learning disabilities, distinctive bony abnormalities, and hyperpigmented lesions (cafe-au-lait macules, skinfold freckling, and Lisch nodules). With the identification of the neurofibromatosis 1 gene in 1990, significant strides have been made towards elucidating the pathogenesis of specific clinical problems in neurofibromatosis type 1 and developing first-generation, biologically based targeted therapies. Recent advances in mouse modeling have likewise yielded important insights into the genetic and cellular mechanisms underlying neurofibromatosis 1-associated tumor formation and learning disabilities. This review will focus on the clinical features of neurofibromatosis type 1, the molecular biology of the neurofibromatosis 1 gene, and the use of mouse modeling to recapitulate the human condition.