Evaluating the role of primary care pharmacy technicians in antimicrobial stewardship (AMS) and acne management using TARGET resources.

Background: Inappropriate antibiotic prescribing is accelerating antimicrobial resistance (AMR) (Antibiotic resistant infections and associated deaths increase  https://www.gov.uk/government/news/antibiotic-resistant-infections-and-associated-deaths-increase). Pharmacy professionals (pharmacists and pharmacy technicians) promote good antibiotic prescribing practice. The traditional role of pharmacy technicians in supporting pharmacists and patients has expanded alongside the clinical expansion of pharmacist roles. (Boughen M, Fenn T. Practice, skill mix and education: the evolving role of pharmacy technicians in Great Britain. Pharmacy (Basel) 2020; 8(2): 50. doi:10.3390/pharmacy8020050) This paper focuses on the opinion of pharmacy technicians and their role in the review of acne management and the evaluation of the UKHSA TARGET acne 'How to…' review resources. Aims and objectives: To explore the impact of the TARGET resources on the capability, opportunity and motivation of pharmacy technicians in general practice in managing patients with acne.To evaluate the usefulness of the acne 'How to…' review resources. Materials and methods: A primarily quantitative study using an electronic survey asking UK-based pharmacy technicians to rate their agreement on a five-point Likert scale with 21 predefined statements, themed on the COM-B model and usefulness of the TARGET resources for acne. Discussion: The survey found that capability and opportunity in managing acne in the group familiar with TARGET resources was higher than the group not familiar with TARGET resources. Scores for motivation in both groups were high; pharmacy technicians have the motivation to undertake infection management roles, whether or not they are familiar with the TARGET toolkit.The acne 'How to…' review resources were overall rated as useful in supporting the review of patients with acne. Conclusion: The TARGET materials are effective resources that helps to upskill pharmacy technicians in the area of AMS, increasing capability and opportunity in the management of acne.

Pairing lab and field studies to predict thermal performance of wild fish.

In thermally variable ecosystems, temperatures can change extensively on hourly and seasonal timescales requiring ectotherms to possess a broad thermal tolerance (critical thermal minima [CTmin] and maxima [CTmax]). However, whether fish acclimate in the laboratory similarly as they acclimatize in the field under comparable thermal variation is unclear. We used temperature data from a tidal salt marsh to design 21-day lab-acclimation treatments (static: 12, 17, 22, 27 °C; daily variation with mean 22 °C: i) range 17-27 °C, ii) range 17-27 °C with irregular extremes within 12-32 °C). We compared thermal limits in lab-acclimated and field-acclimatized eurythermal arrow goby (Clevelandia ios). Variable temperature-acclimated and acclimatized fish had similar CTmin and CTmax. Notably, arrow gobies showed rapid plasticity in their absolute thermal tolerance within one tidal cycle. The daily mean and max temperatures experienced were positively related to CTmax and CTmin, respectively. This study demonstrates that ecologically informed lab acclimation treatments can yield tolerance results that are applicable to wild fish.

Adaptive Long-Read Sequencing Reveals GGC Repeat Expansion in ZFHX3 Associated with Spinocerebellar Ataxia Type 4.

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.

How can community pharmacists be supported to manage skin conditions? A multistage stakeholder research prioritisation exercise.

OBJECTIVE: To establish research priorities which will support the development and delivery of community pharmacy initiatives for the management of skin conditions. DESIGN: An iterative, multistage stakeholder consultation consisting of online survey, participant workshops and prioritisation meeting. SETTING: All data collection took place online with participants completing a survey (delivered via the JISC Online Survey platform, between July 2021 and January 2022) and participating in online workshops and meetings (hosted on Microsoft Teams between April and July 2022). PARTICIPANTS: 174 community pharmacists and pharmacy staff completed the online survey.53 participants participated in the exploratory workshops (19 community pharmacists, 4 non-pharmacist members of pharmacy staff and 30 members of the public). 4 healthcare professionals who were unable to attend a workshop participated in a one-to-one interview.29 participants from the workshops took part in the prioritisation meeting (5 pharmacists/pharmacy staff, 1 other healthcare professional and 23 members of the public). RESULTS: Five broad areas of potential research need were identified in the online survey: (1) identifying and diagnosing skin conditions; (2) skin conditions in skin of colour; (3) when to refer skin conditions; (4) disease-specific concerns and (5) product-specific concerns.These were explored and refined in the workshops to establish 10 potential areas for research, which will support pharmacists in managing skin conditions. These were ranked in the prioritisation meeting. Among those prioritised were topics which consider how pharmacists work with other healthcare professionals to identify and manage skin conditions. CONCLUSIONS: Survey responses and stakeholder workshops all recognised the potential for community pharmacists to play an active role in the management of common skin conditions. Future research may support this in the generation of resources for pharmacists, in encouraging public take-up of pharmacy services, and in evaluating the most effective provision for dealing with skin conditions.

A model of purchase intention of complementary and alternative medicines: the role of social media influencers' endorsements.

BACKGROUND: Social Media Influencers (SMIs) are a fashionable way of marketing products by creating electronic word-of-mouth (e-WOM) on social media. The marketing of complementary and alternative medicines (CAMs) by SMIs is becoming increasingly popular and gaining credibility within consumers on social media platforms. Nonetheless, advising about healthcare products on social media should be examined as it is different from endorsing other kinds of commercial products. The aim of this study is to develop a model that provides the underlying mechanisms of the stimuli of SMIs on social media towards consumers' purchase intention of CAMs. METHODS: This study used best fit framework synthesis methods to develop the model. A priori theory selection was conducted by identifying a BeHEMoTh strategy (Behavior of Interest, Health context, Exclusions and Models or Theories) to systematically approach identifying relevant models and theories relative to the research aim. Further evidence derived from primary research studies that describe the behavior identified is coded against selected a priori theory to develop the model. RESULTS: This study presents a novel model for understanding the purchase behavior of CAMs using SMIs as a marketing strategy. The model included two well-known theories (theory of planned behaviour theory and source credibility theory) as well as extensive existing research from a multidisciplinary perspective. The model is exclusively designed to help identify elements affecting perceived source credibility and factors that have an influence over consumers' preferences to purchase CAMs by taking into consideration SMIs' endorsements. CONCLUSIONS: This study provides unique insights introducing new research areas to health literature and offers, new roles for healthcare professionals in this digital era by gaining new skills and competencies required to provide more credible and accurate information about CAMs. The study also highlights the new marketing era of online health-related product endorsements and recommends that policymakers and researchers carefully evaluate the impact of SMI's on the use of CAMs, as well as to regulate the content of these promotional materials.

Sunlight Inactivation of Enveloped Viruses in Clear Water.

Enveloped virus fate in the environment is not well understood; there are no quantitative data on sunlight inactivation of enveloped viruses in water. Herein, we measured the sunlight inactivation of two enveloped viruses (Phi6 and murine hepatitis virus, MHV) and a nonenveloped virus (MS2) over time in clear water with simulated sunlight exposure. We attenuated UV sunlight wavelengths using long-pass 50% cutoff filters at 280, 305, and 320 nm. With the lowest UV attenuation tested, all decay rate constants (corrected for UV light screening, k̂) were significantly different from dark controls; the MS2 k̂ was equal to 4.5 m2/MJ, compared to 16 m2/MJ for Phi6 and 52 m2/MJ for MHV. With the highest UV attenuation tested, only k̂ for MHV (6.1 m2/MJ) was different from the dark control. Results indicate that the two enveloped viruses decay faster than the nonenveloped virus studied, and k̂ are significantly impacted by UV attenuation. Differences in k̂ may be due to the presence of viral envelopes but may also be related to other differing intrinsic properties of the viruses, including genome length and composition. Reported k̂ values can inform strategies to reduce the risk from exposure to enveloped viruses in the environment.

Evaluation of The Rational Drug Use (RDU) Literacy Among Undergraduate Students

Background: Irrational drug usage is a global concern. WHO recommended a strategy for integrating education and awareness on the rational use of medicine into general education programs. Objective: To evaluate the rational drug use (RDU) literacy among the undergraduate students of Ubon Ratchathani University. Methods: This mixed-methods research consists of a quantitative cross-sectional study with a self-administered RDU literacy questionnaire and a qualitative in-depth interview study. Descriptive statistics and inferential statistics were used in the quantitative study. Thematic analysis was used in the qualitative study. Results: Students who participated in this study included 640 undergraduate students. Approximately half of the participants never studied a RDU-related course (50.94%). Although the findings revealed that most of the participants (73.13%) had good RDU literacy, many participants had less frequency of the right options on some questions (e.g., advertisement of health products). Health sciences students were 2.8 times more likely than non-health sciences students to have good RDU literacy (AOR=2.835, 95% CI: 1.752-4.587). Four main themes were derived from the qualitative study: 1. Definition of RDU; 2. Facilitators; 3. Concerns; 4. RDU country. Conclusion: While the majority of participants demonstrated good RDU literacy, some actually engaged in irrational drug use. Activities promoting RDU literacy among undergraduate students, particularly in faculties other than health sciences, are still required (AU)

Facilitators and barriers of the rational drug use hospital program in Thailand

The Thailand Ministry of Public Health has started a rational drug use (RDU) policy, which includes multifaceted strategies as well as the RDU hospital program to tackle irrational drug use. Objective: To investigate facilitators and barriers related to the CIPP model of the RDU hospital program in Thailand. Methods: This is a qualitative study. Data were collected through semi-structured interviews with regional policymakers who were members of the executive board for RDU management in the 10th health region. The interviews were conducted via telephone using a topic guide informed by the CIPP framework and reviewed for content validity by the research team. Data were transcribed, and thematically analyzed. Results: Fifteen pharmaceutical policymakers were interviewed. The main facilitators related to context, input, and process were the national policy on RDU, RDU awareness/practices among health professionals, particularly prescribers, and multidisciplinary teamwork under the organization’s leadership to use data feedback to improve the program. The main barriers related to context, input, and process were a lack of policy advocacy at the regional and provincial levels, doctor-related reasons such as medicolegal concerns, and a lack of multidisciplinary teamwork. For the product theme, participants were very satisfied and perceived positive impacts at both the individual and organizational levels, such as increased RDU awareness in patients and multidisciplinary teams, as well as RDU prescription. However, negative impacts, such as tensions surrounding professional responsibility and accountability, have been observed. (AU)

Perceived current and future roles of UK-based community pharmacy professionals in the long-term management of acne.

Introduction: Acne is a common skin condition treated in community pharmacy but moderate to severe cases may need referral to general practice for treatment that may include topical or oral antimicrobial treatments. Pharmacy teams working in the community are well-placed to manage acne treatments in line with NICE guidance. Objectives: To explore the perceived current and future roles of community pharmacy (CP) teams alongside needs to achieve potential future roles. Additionally, usefulness of the TARGET acne 'How to' toolkit to support these roles was sought. Methods: A mixed-methods electronic survey of UK-based CP professionals and stakeholders in March 2023. Results: 54 pharmacy professionals and stakeholders responded to the survey. The current confidence of pharmacy professionals in managing acne was rated as moderate and reviewing long-term medications for acne prescribed by another healthcare professional was seen as a future role. The needs identified to undertake such a role were: training, availability of prescribing or supply frameworks, and appropriate remuneration. The TARGET acne resources were thought of as being very useful for acne management. Conclusions: Potential future roles for CP have been identified, alongside additional needs to undertake these roles; the TARGET acne 'How to' resources could support pharmacy professionals in the management and review of antimicrobial treatment for acne.

Enveloped and non-enveloped virus survival on microfiber towels.

Background: Handwashing is an important intervention which can reduce indirect disease transmission, however soap and water for handwashing purposes is not available in some low-resource regions. When handwashing with soap and water is not possible, individuals may use alternatives such as the Supertowel (a microfiber towel with an antimicrobial coating). Testing of viral inactivation as a result of antimicrobial treatment on the Supertowel, however, has been limited. The goal of this study is to provide information about the performance of the Supertowel's antimicrobial treatment against viruses, which will help inform the use of the towels as handwashing alternatives. Methods: We seeded the Supertowel and a regular microfiber towel with two bacteriophages (enveloped Phi6 and non-enveloped MS2) and monitored viral inactivation over time. Additionally, we assessed if temperature, humidity, whether the towel was initially wet or dry, or virus type had an effect on viral decay rate constants. Virus concentrations were measured repeatedly over 24 h. Results: We found that neither towel type (whether the towel was a Supertowel or a regular microfiber towel) nor humidity were significant variables in our model of decay rate constants (P = 0.06 and P = 0.22, respectively). We found that the variables of temperature, whether towels were initially wet versus dry, and virus type were significantly different from 0, suggesting that these variables explained variance in the decay rate constant (P = 6.55 × 10-13, P = 0.001, and P < 2 × 10-16, respectively). Higher temperatures, dry towels, and enveloped viruses all resulted in increases in the decay rate constant. Conclusions: Viruses seeded onto a Supertowel decay similar to viruses seeded onto a regular towel indicating that the virucidal potential of the Supertowel is minimal.

Age-dependent dysregulation of locus coeruleus firing in a transgenic rat model of Alzheimer's disease.

Hyperphosphorylated tau in the locus coeruleus (LC) is ubiquitous in prodromal Alzheimer's disease (AD), and LC neurons degenerate as AD progresses. Hyperphosphorylated tau alters firing rates in other brain regions, but its effects on LC neurons are unknown. We assessed single unit LC activity in anesthetized wild-type (WT) and TgF344-AD rats at 6 months, which represents a prodromal stage when LC neurons are the only cells containing hyperphosphorylated tau in TgF344-AD animals, and at 15 months when amyloid-ß (Aß) and tau pathology are both abundant in the forebrain. At baseline, LC neurons from TgF344-AD rats were hypoactive at both ages compared to WT littermates but showed elevated spontaneous bursting properties. Differences in footshock-evoked LC firing depended on age, with 6-month TgF344-AD rats demonstrating aspects of hyperactivity, and 15-month transgenic rats showing hypoactivity. Early LC hyperactivity is consistent with appearance of prodromal neuropsychiatric symptoms and is followed by LC hypoactivity which contributes to cognitive impairment. These results support further investigation into disease stage-dependent noradrenergic interventions for AD.

Bendamustine plus rituximab for the treatment of Waldenström Macroglobulinemia: Patient outcomes and impact of bendamustine dosing.

Bendamustine and rituximab (BR) therapy is commonly used in the treatment of Waldenström Macroglobulinemia (WM). The impact dose of Bendamustine dose on response and survival outcomes is not well-established, and the impact of its use in different treatment settings is not clear. We aimed to report response rates and survival outcomes following BR, and clarify the impact of depth of response and bendamustine dose on survival. A total of 250 WM patients treated with BR in the frontline or relapsed settings were included in this multicenter, retrospective cohort analysis. Rates of partial response (PR) or better differed significantly between the frontline and relapsed cohorts (91.4% vs 73.9%, respectively; p < 0.001). Depth of response impacted survival outcomes: two-year predicted PFS rates after achieving CR/VGPR vs PR were 96% versus 82%, respectively (p = 0.002). Total bendamustine dose was predictive of PFS: in the frontline setting, PFS was superior in the group receiving ≥1000 mg/m2 compared with those receiving 800-999 mg/m2 (p = 0.04). In the relapsed cohort, those who received doses of <600 mg/m2 had poorer PFS outcomes compared with those who received ≥600 mg/m2 (p = 0.02). Attaining CR/VGPR following BR results in superior survival, and total bendamustine dose significantly impacts response and survival outcomes, in both frontline and relapsed settings.

A gene regulatory network for neural induction.

During early vertebrate development, signals from a special region of the embryo, the organizer, can redirect the fate of non-neural ectoderm cells to form a complete, patterned nervous system. This is called neural induction and has generally been imagined as a single signalling event, causing a switch of fate. Here, we undertake a comprehensive analysis, in very fine time course, of the events following exposure of competent ectoderm of the chick to the organizer (the tip of the primitive streak, Hensen's node). Using transcriptomics and epigenomics we generate a gene regulatory network comprising 175 transcriptional regulators and 5614 predicted interactions between them, with fine temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization, single-cell RNA-sequencing, and reporter assays, we show that the gene regulatory hierarchy of responses to a grafted organizer closely resembles the events of normal neural plate development. The study is accompanied by an extensive resource, including information about conservation of the predicted enhancers in other vertebrates.

Thai stakeholders' awareness and perceptions of the patient adverse event reporting system for herbal medicines: a qualitative study.

BACKGROUND: In Thailand, the consumption of herbal medicines has been increasing. Adverse events (AEs) of herbal medicines have been identified through the spontaneous reporting system. However, the number of patients reporting AEs of herbal medicines remains limited. AIM: To explore the awareness and perceptions about the patient reporting system and to explore attitudes towards safety of herbal medicines, experiences, and intention to report AEs of herbal medicines. METHOD: Semi-structured in-depth interviews were conducted with stakeholders (patients, community pharmacists, village health volunteers, and consumers who had experienced submitting a complaint about health products to the Consumers Foundation). Additionally, a focus group discussion was held with stakeholders (academics, herbal medicine manufacturers, healthcare professionals, policy maker who was responsible for promoting the use of herbal medicines, pharmacovigilance staff, patient, and representative from patient organisations). The data were audio recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Fifty participants were interviewed and the focus group discussion included 12 participants. Patients had positive attitudes towards the safety of herbal medicines. Lack of awareness of the patient reporting system was identified. Nevertheless, all stakeholders acknowledged the importance of the safety monitoring of herbal medicines and indicated a willingness to report AEs via the patient reporting system in the future. A simple reporting system, a variety of reporting channels, the provision of feedback, and providing rewards would motivate patients to report AEs. CONCLUSION: Although there is a lack of awareness, this provides a great opportunity to improve patient AE reporting system for herbal medicines in Thailand.

Investigating the Efficacy of Various Handwashing Methods against Enveloped and Non-Enveloped Viruses.

Respiratory and diarrheal diseases are leading causes of death worldwide. Handwashing may reduce disease; however, recommended methods (soap and water for 20 seconds) are not always possible, particularly in low-resource settings. The aim of this study is to evaluate handwashing when recommended methods are not feasible, including washing with water only, washing with soapy water, washing for a short duration, using alcohol-based hand sanitizer (ABHS), and cleaning hands with towels. To evaluate laboratory efficacy, we seeded MS2 (a non-enveloped virus) and Phi6 (an enveloped virus) onto the hands of volunteers who then washed their hands. Viruses remaining were recovered and quantified using culture-based and molecular methods to determine the log reduction value (LRV) after washing. Results indicated that washing with water only and with soapy water were similar to washing with soap and water for 20 seconds for both viruses (median LRV for MS2 = 2.8; Phi6 = 3.2). Most towel alternative conditions had LRVs significantly smaller than LRVs from washing with soap and water for either virus. LRVs of ABHS and soap and water for 5 seconds were similar to soap and water for 20 seconds for Phi6 but less for MS2 (median MS2 LRV differences = 2.5 and 0.51 for ABHS and soap and water for 5 seconds, respectively). Additionally, LRVs determined using molecular methods were in agreement with those obtained using culture-based methods. These results suggest some handwashing alternatives were as effective as recommended methods whereas others were not, and inform recommendations and future research on handwashing alternatives in low-resource settings.

A systematic review of contemporary competency-based education and training for pharmacy practitioners and students.

BACKGROUND: The use of competency-based education (CBE) worldwide is increasing and has been advocated for by key reports in health professional education. Recent developments, including the first global competency framework for pharmacists published by the International Pharmaceutical Federation (FIP) in 2012, can help facilitate CBE adoption. However, adopting CBE is complex and involves various features and stages of development. OBJECTIVE: This systematic review examines pharmacy education and training to identify features of CBE-related approaches currently in use worldwide to develop a picture of contemporary CBE-related activity in pharmacy for the purpose of guiding future development. METHOD: Scopus, Web of Science, Medline, Embase, and ERIC electronic databases were searched to identify relevant literature. Studies associated with CBE or training of pharmacy practitioners and related postgraduate or undergraduate students were included. Studies were limited to those published in English from 2010 to 2021. Two authors performed the screening and selection of studies, and a 3rd author resolved any discrepancies. The review followed PRSIMA guidelines and was registered with PROSPERO under CRD42022296424. The findings were analysed using an inductive approach and presented descriptively. RESULTS: Twenty-eight studies were included in the review, all of which originate from high-income countries, spanning a range of educational levels and research designs. A total of 20 features and 21 supporting components were identified and categorised, connected to those previously identified in the closely linked medical literature, and categorised into 6 overarching themes: design, teaching and learning, feedback and assessment, faculty, resources, and internal and external factors. A collective understanding of the concept of competency, in combination with a shared vision between education, regulation, and practice, underpins successful application of the CBE approach. CONCLUSIONS: This review summarises common features of CBE across the globe which can be used to guide further developments in pharmacy education. Mutual consensus on the design and delivery of CBE features ensures that the intended learning outcomes are in alignment with the learner's experience and congruent with the realities of pharmacy practice.

Quantifying the Viral Reduction Achieved Using Ash and Sand as Handwashing Agents.

The WHO recommends handwashing with soap and water for 20-40 seconds. In settings where soap is not available, ash or sand is used for handwashing, yet their efficacy as handwashing materials is underresearched. The purpose of this study was to quantify the removal of viruses using ash and sand as handwashing agents, and compare their efficacy to commonly recommended handwashing methods. We performed a volunteer study to estimate the log reduction value (LRV) of model viruses Phi6 and MS2 on hands after six handwashing conditions: two handwashing agents (ash and water, and sand and water) with two time points (5 and 20 seconds), and two handwashing agents (soap and water, and water only) with one time point (20 seconds). Plaque assays were used to measure infectious virus reduction. Handwashing with any of the handwashing agents for 20 seconds resulted in a greater LRV than the 2-log reduction U.S. Food and Drug Administration criteria for both viruses. Soap and water resulted in a significantly greater LRV (2.7-4.8) than washing with ash and water (2.0-2.8) or sand and water (1.8-2.7) for 5 seconds for both viruses, and water only resulted in a significantly higher LRV (2.8) than all ash (2.0-2.6) and sand (1.8-2.4) conditions for MS2 only. These results suggest that using ash or sand as handwashing agents can be efficacious in reducing viruses but may be less efficacious than soap, especially when used for shorter durations. Further research should investigate the use of ash and sand as handwashing agents in real-world settings.

Logic model for opioid safety in chronic non-malignant pain management, an in-depth qualitative study.

BACKGROUND: Opioids are commonly used for the management of chronic non-malignant pain in Pakistan; but there is a lack of literature around precursors or motivators in the use of opioids. AIM: The study holistically explored factors contributing towards the unsafe use of opioids and identifies strategies to overcome them. METHOD: Exploratory qualitative methods using interviews, focus groups and non-participant observational case studies were used. Interviews and focus groups were carried out face-to-face as well as virtually and observations were conducted in community pharmacies in Islamabad and Khyber Pukhtoon Khuwa province, Pakistan. Data were collected from 4 stakeholder groups; pharmacy policy makers (n = 11), people with chronic non-malignant pain (n = 14), doctors (n = 31) and community pharmacists (n = 36) by purposive critical case sampling method. Data were analysed inductively using reflexive thematic analysis and then deductively mapped to a social ecological framework. Non-participant observations were analysed using a cross case synthesis using explanation building technique. Data from all three methods were triangulated to develop a logic model. RESULTS: Identified factors at macro (regulation), meso (social perceptions of pain and opioids) and micro levels (uncontrolled pain, self-medication, health literacy) and strategies are presented holistically and were used to develop a logic model for the prevention and mitigation of factors currently causing unsafe use of opioids. CONCLUSION: The study provides an in-depth view of factors contributing towards diversion of pharmaceutical opioids and can help guide national and international policy makers in their future initiatives to promote safe use of opioids in the management of chronic non-malignant pain in Pakistan.

Identification of candidate hub genes correlated with the pathogenesis, diagnosis, and prognosis of prostate cancer by integrated bioinformatics analysis.

Background: Prostate cancer (PCa) has the second highest morbidity and mortality rates in men. Concurrently, novel diagnostic and prognostic biomarkers of PCa remain crucial. Methods: This study utilized integrated bioinformatics method to identify and validate the potential hub genes with high diagnostic and prognostic value for PCa. Results: Four Gene Expression Omnibus (GEO) datasets including 123 PCa samples and 76 normal samples were screened and a total of 368 differentially expressed genes (DEGs), including 120 up-regulated DEGs and 248 down-regulated DEGs, were identified. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the DEGs were majorly enriched in focal adhesion, chemical carcinogenesis, drug metabolism, and cytochrome P450 pathways. Then, 11 hub genes were identified from the protein-protein interaction (PPI) network of the DEGs; 7 of the 11 genes showed the ability of distinguishing PCa from normal prostate based on receiver operating characteristic (ROC) curve analysis. And 5 of the 11 genes were correlated with clinical attributes. Lower CAV1, KRT5, SNAI2 and MYLK expression level were associated with higer Gleason score, advanced pathological T stage and N stage. Lower KRT5 and MYLK expression level were significantly correlated with poor disease-free survival, and lower KRT5 and PTGS2 expression level were significantly related to biochemical recurrence (BCR) status of PCa patients. Conclusions: In conclusion, CAV1, KRT5, SNAI2, and MYLK show potential clinical diagnostic and prognostic value and could be used as novel candidate biomarkers and therapeutic targets for PCa.