Community Pharmacists' Views on the Early Stages of Implementation of a National Pilot Independent Prescribing Service in Wales: A Qualitative Study.

Background: A pilot Independent Prescribers' Service (IPS) was introduced in 13 community pharmacies across Wales in June 2020. Independent Pharmacist Prescribers (IPPs) could prescribe in the areas of management of acute conditions, contraception, or opioid withdrawal, as agreed with local commissioners. Access to the patients' medical records was provided via Choose Pharmacy, the national community pharmacy IT platform. Objective: To explore the experiences of IPPs delivering the service and commissioners responsible for financial resources regarding the IPS in Wales. Methods: A qualitative methodology was employed, with purposive sampling, semi-structured interviews, and inductive thematic analysis. Results: Five themes were constructed from 13 interviews (n=9 IPPs; n=4 commissioners): (i) patient experience and safety; (ii) professional enablement and rebalancing workload of GPs; (iii) role and limitations of remote consultations; (iv) funding and business model; (v) functionality on Choose Pharmacy to support patient care. The design of the service allowed pharmacists to determine how best to deliver the IPS, maximizing access for patients and promoting a sense of professional value amongst pharmacists. Conclusion: This study builds on the body of evidence on enhanced patient experience with prescribing services in the community, reinforcing that IPPs have a key role in rebalancing management of common conditions from GP surgeries to community pharmacies. Several considerations need to be addressed to ensure future success of the service implementation, delivery and enhanced sustainability, such as formal referral pathways and access to medical records. These can be used by other commissioning bodies in the UK and internationally to build a network of suitably supported IPPs, confident to appropriately deal with uncomplicated acute and chronic conditions; and liaise with primary and/or secondary care when referrals are needed.

Wearable Sensor-Based Detection of Influenza in Presymptomatic and Asymptomatic Individuals.

BACKGROUND: The COVID-19 pandemic highlighted the need for early detection of viral infections in symptomatic and asymptomatic individuals to allow for timely clinical management and public health interventions. METHODS: Twenty healthy adults were challenged with an influenza A (H3N2) virus and prospectively monitored from 7 days before through 10 days after inoculation, using wearable electrocardiogram and physical activity sensors. This framework allowed for responses to be accurately referenced to the infection event. For each participant, we trained a semisupervised multivariable anomaly detection model on data acquired before inoculation and used it to classify the postinoculation dataset. RESULTS: Inoculation with this challenge virus was well-tolerated with an infection rate of 85%. With the model classification threshold set so that no alarms were recorded in the 170 healthy days recorded, the algorithm correctly identified 16 of 17 (94%) positive presymptomatic and asymptomatic individuals, on average 58 hours postinoculation and 23 hours before the symptom onset. CONCLUSIONS: The data processing and modeling methodology show promise for the early detection of respiratory illness. The detection algorithm is compatible with data collected from smartwatches using optical techniques but needs to be validated in large heterogeneous cohorts in normal living conditions. Clinical Trials Registration. NCT04204493.

Affymetrix oligonucleotide analysis of gene expression in the injured heart.

Microarrays have helped researchers gain much insight into gene expression profiles in the context of many diseases including those in the injured heart. Our genomic investigations have been focused on elucidation of host gene responses to enterovirus infection. We have gained valuable technical expertise in using Affymetrix oligonucleotide arrays, also known as GeneChips, and cDNA spotted arrays to probe differential gene expression in both cultured cells and in heart tissue. Here, we provide a technique-focused supplement to the Affymetrix GeneChip Expression Analysis Manual for sample preparation, processing, and array hybridization. We provide expanded explanations to highlight important points within the existing protocol and offer variations to standard procedures when appropriate. For investigators using myocardial tissues for microarray experiments, we further address the necessity of and methods for in situ flushing of the vasculature, tissue homogenization, and considerations for limits of expression detection in rare cells. It is our intention to provide useful technical information, based on our experience, to assist those researchers using Affymetrix GeneChips in their own genomic research.

Molecular markers in the endometrium at baseline of postmenopausal patients with early breast cancer in the ATAC (Arimidex, tamoxifen, alone, or in combination) trial.

OBJECTIVE: This study was undertaken to assess baseline endometrial molecular events in the ATAC (Arimidex, tamoxifen, alone, or in combination) trial of breast cancer adjuvant therapy. STUDY DESIGN: Estrogen receptor (ER) and progesterone receptor (PR) levels and markers of cell proliferation (Ki67) and apoptosis ( Bcl -2) were assessed in 93 patients at baseline. RESULTS: An inactive/atrophic endometrium was found in 63 patients, 5 had a proliferative endometrium, and 12 had a secretory endometrium. Thirteen endometrial polyps were analyzed. Inactive endometrium showed high levels of ER in the glandular epithelium, whereas in more than 50% of samples, PR expression was negative or low (+) in the glandular epithelium, and stroma. Ki67 expression was low in both the glandular epithelium and the stroma of the inactive endometrium, whereas Bcl -2 expression was mostly high or very high (+++/++++) in the glandular epithelium. Bcl -2 was strongly expressed (+++/++++) in the glandular epithelium of polyps. CONCLUSION: Although all patients were asymptomatic, some had endometrial pathology.

The differential expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67 in endometrial polyps.

OBJECTIVE: To obtain a greater understanding of the pathogenesis of endometrial polyps and to gain insight into which factors play a pivotal role in their growth. DESIGN: Retrospective analysis of archived paraffin-embedded specimens. SETTING: St James's University Hospital. SAMPLE: Thirty secretory phase endometrial samples, 10 secretory phase endometrial polyps, 8 proliferative phase endometrial samples and 10 proliferative phase endometrial polyps. METHODS: Immunohistochemistry was used to characterise the expression of oestrogen and progesterone receptors, Bcl-2 and Ki67 in cycling endometrium and phase-matched endometrial polyps. Patterns of expression were compared between the polyps and the endometrium. MAIN OUTCOME MEASURE: The expression of oestrogen receptors, progesterone receptors, Bcl-2 and Ki67. RESULTS: Three significant differences were found between the endometrium and the polyps. Polyps taken from the proliferative phase of the cycle displayed significantly elevated expression of Bcl-2 and weak or no expression of progesterone receptors. Secretory phase polyps displayed an elevated expression of oestrogen receptors. CONCLUSION: A localised increase in Bcl-2 expression and consequential decline or cessation of apoptosis is an important mechanism underlying the pathogenesis of endometrial polyps. Elevated Bcl-2 expression results in failure of the polyp tissue from undergoing normal cyclical apoptosis during the late secretory phase. This may mean the polyp is not shed along with the rest of the endometrium during menstruation.

Genetic determinants of coxsackievirus B3 pathogenesis.

The development of high throughput genomic and bioinformatic analysis tools, coupled with established molecular techniques, has allowed new insights into the pathogenesis of infectious diseases. In humans, coxasackievirus B3 (CVB3) is the primary etiological agent of viral myocarditis, an inflammatory disease process involving the heart muscle. Early host cellular survival and apoptotic mechanisms during viral infections, as well as immune events, affect myocarditis progression and outcome. Therefore, our laboratory has been keenly interested in infectomics, defined here as the transcriptional events of both virus and host. We first elucidated up- or downregulated transcriptional activities in CVB3-infected hearts by mRNA differential display. Further characterization of these regulated genes including Nip21, IP10, and IGTPase, and study of their role in CVB3-infection are underway. In further dissection of the stages of myocarditis-peak viremia, inflammatory infiltration and tissue repair-we used cDNA microarrays to probe differential gene expression in the myocardium following virus infection. Following virus infection, there are global decreases in metabolic and mitochondrial genes, increases in signaling genes and distinctive patterns in other functional groups. To establish early gene expression profiles in infected cells by themselves, we also used oligonucleotide arrays in an in vitro model of CVB3 infection. Notably, we have found increased expression of transcription factors c-fos and c-jun down-stream of extracellular signal-related kinase, a pathway which is crucial for virus replication and pathogenesis. Our investigations based on gene profiling following CVB3 infection have thus far been fruitful in providing new experimental leads. High throughput genetic analysis has allowed us to simultaneously try on greater than 12,000 potential genetic "glass slippers." Our in vitro experimental plan has enabled us to chart prominent patterns of gene expression, analyzed by novel bioinformatic approaches, and to separate varied and potentially significant gene expression events.