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Background: Providing primary care for people with frailty can be challenging due to an increased risk of adverse outcomes and use of potentially inappropriate medications which may exacerbate characteristics of frailty. eConsult is a service where primary care providers can receive timely specialist advice for their patients through a secure web-based application. We aimed to develop a classification system to characterize medication-focused eConsult questions for older adults with frailty and assess its usability. Methods: A classification system was developed and refined over three cycles of improvement through a cross-sectional study of 35 cases categorized as medication-focused from cases submitted in 2019 for patients aged 65 or older with frailty through the Champlain BASE eConsult service (Ontario, Canada). The final classification system was then applied to each case. Results: The classification system contains 5 sections: (1) case descriptives; (2) intent and type of question; (3) medication recommendations and additional information in the response; (4) medication classification; and (5) potentially inappropriate medications. Among the 35 medication-focused cases, the most common specialties consulted were endocrinology (9 cases, 26%) and cardiology (5 cases, 14%). Medication histories were available for 29 cases (83%). Many patients were prescribed potentially inappropriate medications based on explicit tools (AGS Beers Criteria®, STOPPFall, Anticholinergic Cognitive Burden Scale, ThinkCascades) yet few consults inquired about these medications. Conclusion: A classification system to describe medication-related eConsult cases for patients experiencing frailty was developed and applied to 35 eConsult cases. It can be applied to more cases to identify professional development opportunities and enhancements for eConsult services. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has heavily affected the economy, industries, and medicine. Local governments and medical institutions have struggled to respond. The purpose of this questionnaire survey was to evaluate strategies for pharmacy services, availability of ethanol for disinfection, and measures adopted for in-house infection control aiming to enhance future infection control efforts.Methods: Since pharmacies have been also affected by the COVID-19 pandemic, we surveyed COVID-19 measures taken at 174 pharmacies in Ehime prefecture, Japan.Results: The survey showed that pharmacies made changes to facilities and equipment, such as installing partitions at dispensing counters, procuring personal protective equipment for employees, and using ethanol for disinfection, even when these items were in short supply. Pharmacies also adopted new strategies, such as holding meetings with suppliers and internal staff via online platforms. Many pharmacies also undertook COVID-19 preventive measures, such as preparing documentation of infection control measures and disinfectants. Moreover, they held lectures and workshops on disinfection and infection control measures.Conclusions: From public health perspectives, pharmacies should adopt measures to prevent infections spread and, if necessary, utilise online tools and other new strategies to achieve this goal. It is also essential to educate the public about infection control, stockpile supplies, and work with hospitals to prevent COVID-19 spreads. [ABSTRACT FROM AUTHOR]

Purpose: Patient-reported experiences are a key source of information on quality in mental health care. Most patient experience surveys are limited to assessments from adults, including those conducted by parents or proxies on behalf of others. The aim of this study was to produce findings to inform development of modules on patient and parent experiences with medication in outpatient CAMHS in Norway, for use in previously validated instruments applied in national surveys., Patients and Methods: We developed survey questions based on a systematic literature review, expert-group consultations, interviews with adolescents and parents, and pretesting of the modules in a pilot study. This study included adolescents aged 12-17 years and parents with experiences from outpatient CAMHS and we present findings from semi-structured interviews., Results: Adolescents with ADHD emphasized the following aspects as important concerning medication use in CAMHS: positive effects of medication like better function and concentration in school and change of behaviour. They also stressed the importance of side effects such as eating problems, nausea, loss of appetite, insomnia, and changes in thoughts and feelings. In addition, adolescents highlighted the significance of aspects as support in daily routines for taking medications, while parents highlighted needs for a professional follow-up care. Parents emphasized aspects regarding their children's medication included both positive effects and change in behaviour, as well as their identification of negative side effects., Conclusion: Our findings from semi-structured interviews identified important aspects reported by both patients and parents on functions, side effects and follow-up care related to medication. The results indicated that both groups emphasized corresponding aspects of what was important regarding medication. However, when it came to follow-up care, the two groups highlighted distinct aspects, indicating differing priorities or concerns in this area., (© 2024. The Author(s).)

Background: Identification of potential drug-target interactions (DTIs) with high accuracy is a key step in drug discovery and repositioning, especially concerning specific drug targets. Traditional experimental methods for identifying the DTIs are arduous, time-intensive, and financially burdensome. In addition, robust computational methods have been developed for predicting the DTIs and are widely applied in drug discovery research. However, advancing more precise algorithms for predicting DTIs is essential to meet the stringent standards demanded by drug discovery., Results: We proposed a novel method called GSRF-DTI, which integrates networks with a deep learning algorithm to identify DTIs. Firstly, GSRF-DTI learned the embedding representation of drugs and targets by integrating multiple drug association information and target association information, respectively. Then, GSRF-DTI considered the influence of drug-target pair (DTP) association on DTI prediction to construct a drug-target pair network (DTP-NET). Next, we utilized GraphSAGE on DTP-NET to learn the potential features of the network and applied random forest (RF) to predict the DTIs. Furthermore, we conducted ablation experiments to validate the necessity of integrating different types of network features for identifying DTIs. It is worth noting that GSRF-DTI proposed three novel DTIs., Conclusions: GSRF-DTI not only considered the influence of the interaction relationship between drug and target but also considered the impact of DTP association relationship on DTI prediction. We initially use GraphSAGE to aggregate the neighbor information of nodes for better identification. Experimental analysis on Luo's dataset and the newly constructed dataset revealed that the GSRF-DTI framework outperformed several state-of-the-art methods significantly., (© 2024. The Author(s).)

Background: Celiac disease (CD) is one of the most common gluten-related disorders. Although the only effective treatment is a strict gluten-free diet, doubts remain as to whether healthcare professionals take this restriction into consideration when prescribing and dispensing medicines to susceptible patients. This scoping review aimed to find out the current evidence for initiatives that either describe the gluten content of medicines or intend to raise awareness about the risk of prescribing and dispensing gluten-containing medicines in patients with CD and other gluten-related disorders. Methods: A scoping review was conducted using three search strategies in PubMed/MEDLINE, TripDatabase and Web of Science in April 2021, following the PRISMA extension for scoping reviews (PRISMA-ScR). References from included articles were also examined. Two researchers screened the articles and results were classified according to their main characteristics and outcomes, which were grouped according to the PCC (Population, Concept and Context) framework. The initiatives described were classified into three targeted processes related to gluten-containing medicines: prescription, dispensation and both prescription and dispensation. Results: We identified a total of 3146 records. After the elimination of duplicates, 3062 articles remained and ultimately 13 full texts were included in the narrative synthesis. Most studies were conducted in the US, followed by Canada and Australia, which each published one article. Most strategies were focused on increasing health professional's knowledge of gluten-containing/gluten-free medications (n = 8), which were basically based on database development from manufacturer data. A wide variability between countries on provided information and labelling of gluten-containing medicines was found. Conclusion: Initiatives regarding the presence of gluten in medicines, including, among others, support for prescribers, the definition of the role of pharmacists, and patients' adherence problems due to incomplete labelling of the medicines, have been continuously developed and adapted to the different needs of patients. However, information is still scarce, and some aspects have not yet been considered, such as effectiveness for the practical use of solutions to support healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: Unused pharmaceuticals are currently a public health problem. This study aimed to identify unused pharmaceuticals, research practices about the disposal methods, classify the medicines according to Anatomical Therapeutic Chemical codes (ATC) and, to determine the number of unused medicines., Methods: The study was designed as a cross-sectional study. Data were collected between April and August 2023 in Burdur-Türkiye by non-probability sampling technique (convenience method). Pharmaceuticals were classified according to ATC. Statistical Package for Social Science SPSS (V.24) package program was used for data analysis., Results: A total of 1120 people, 1005 in the first sample group and 115 in the second sample group, participated in the study. Findings of first sample group: A total of 4097 boxes of unused pharmaceuticals (4.7 ± 4.3 boxes/per capita) were detected. It was found that pharmaceuticals were stored in areas such as kitchens (59.1%) and refrigerators (38.6%), the reason for keeping them was reuse (41%), and the disposal practice was household garbage (81%). Paracetamol (648 boxes), Other cold preparation (303 boxes), Dexketoprofen (239 boxes), Diclofenac (218 boxes), Amoxicillin and beta-lactamase inhibitor (190 boxes) were found to be the most frequently unused pharmaceuticals. Using the unused medicines at home without consulting a physician was 94.1% (self-medication). Findings of second sample group: Of the 6189 dosage forms in 265 boxes pharmaceutical, 3132(50.6%) dosage forms were used and 3057(49.4%) were found to be unused., Conclusion: There is a significant amount and number of unused medicines in households, and self-medication is common. Medicines are not properly disposed of and some of them expire. Public information is needed. A "drug take-back system" for unused medicines can be useful in solving this problem., (© 2024. The Author(s).)

Background: The co-administration of drugs known to interact greatly impacts morbidity, mortality, and health economics. This study aims to examine the drug-drug interaction (DDI) phenomenon with a large-scale longitudinal analysis of age and gender differences found in drug administration data from three distinct healthcare systems., Methods: This study analyzes drug administrations from population-wide electronic health records in Blumenau (Brazil; 133 K individuals), Catalonia (Spain; 5.5 M individuals), and Indianapolis (USA; 264 K individuals). The stratified prevalences of DDI for multiple severity levels per patient gender and age at the time of administration are computed, and null models are used to estimate the expected impact of polypharmacy on DDI prevalence. Finally, to study actionable strategies to reduce DDI prevalence, alternative polypharmacy regimens using drugs with fewer known interactions are simulated., Results: A large prevalence of co-administration of drugs known to interact is found in all populations, affecting 12.51%, 12.12%, and 10.06% of individuals in Blumenau, Indianapolis, and Catalonia, respectively. Despite very different healthcare systems and drug availability, the increasing prevalence of DDI as patients age is very similar across all three populations and is not explained solely by higher co-administration rates in the elderly. In general, the prevalence of DDI is significantly higher in women - with the exception of men over 50 years old in Indianapolis. Finally, we show that using proton pump inhibitor alternatives to omeprazole (the drug involved in more co-administrations in Catalonia and Blumenau), the proportion of patients that are administered known DDI can be reduced by up to 21% in both Blumenau and Catalonia and 2% in Indianapolis., Conclusions: DDI administration has a high incidence in society, regardless of geographic, population, and healthcare management differences. Although DDI prevalence increases with age, our analysis points to a complex phenomenon that is much more prevalent than expected, suggesting comorbidities as key drivers of the increase. Furthermore, the gender differences observed in most age groups across populations are concerning in regard to gender equity in healthcare. Finally, our study exemplifies how electronic health records' analysis can lead to actionable interventions that significantly reduce the administration of known DDI and its associated human and economic costs., (© 2024. The Author(s).)

Background: Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD., Methods: The project adopts a multidisciplinary approach, where the primary cohort for analysis will consist of approximately 250 patients in Norway, observed during the period of 2022-2026. Cohorts for comparative analysis will include all HAT-patients in Denmark from 2010 to 2022 (N = 500) and all Norwegian patients in conventional OAT (N = 8300). Data comes from individual in-depth and semi-structured interviews, self-report questionnaires, clinical records, and national registries, collected at several time points throughout patients' courses of treatment. Qualitative analyses will use a flexible inductive thematic approach. Quantitative analyses will employ a wide array of methods including bi-variate parametric and non-parametric tests, and various forms of multivariate modeling., Discussion: The project's primary strength lies in its comprehensive and longitudinal approach. It has the potential to reveal new insights on whether pharmaceutical heroin should be an integral part of integrated conventional OAT services to individually tailor treatments for patients with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some do not succeed with conventional OAT will strengthen the knowledge base for drug treatment in general. Results will be disseminated to the scientific community, clinicians, and policy makers., Trial Registration: The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK), ref.nr.:195733., (© 2024. The Author(s).)

Background: Medicine smuggling poses a serious public health threat, limiting patients' safe and timely access to this essential resource. Thus, this study aims to identify the factors contributing to the vulnerability to medicine smuggling and propose effective strategies to combat this issue in Iran., Methods: An analysis of news media was conducted using qualitative content analysis. News text items related to medicine smuggling were retrieved from various online news sources between March 21, 2017, and May 21, 2023. To select health-oriented and general online news stations, news agencies, and newspapers, the purposeful sampling method with a maximum variation strategy was used. The selected sources included Mehr News Agency, Khabar Online, Islamic Consultative Assembly News Agency (ICANA), Islamic Republic News Agency (IRNA), Iranian Students News Agency (ISNA), Hamshahri, Donya-e-Eqtesad newspapers, Webda, Sepid Online, and Iran's Food and Drug Administration News Agency (IFDANA). All data coding was manually done using Microsoft Excel software version 2016., Results: A total of 277 news articles were found to meet the established criteria for inclusion. The analysis revealed four main themes, each with several sub-themes, that shed light on the factors that drive vulnerability and the strategies to combat medicine smuggling. These themes are the economic environment, government and stewardship, information technology systems, and socio-cultural factors. The economic environment emerged as the most significant theme, encompassing medicine selection, reimbursement, and procurement, all of which affect the smuggling of pharmaceuticals in Iran., Conclusion: To combat medicine smuggling, it is important to adjust policies based on the identified vulnerabilities. Effective strategies to reverse pharmaceutical smuggling include capacity building of pharmaceutical manufacturing companies, implementing regulated and enhanced supervisory and rulemaking policies, strengthening health insurance, improving e-infrastructure, and increasing public awareness through collaborative approaches involving various stakeholders within and outside the health system., (© 2024. The Author(s).)

Background: Antimicrobial resistance (AMR) causes high levels of global mortality. There is a global need to develop new antimicrobials to replace those whose efficacy is being eroded, but limited incentive for companies to engage in R&D, and a limited pipeline of new drugs. There is a recognised need for policies in the form of 'push' and 'pull' incentives to support this R&D. This article discusses China, a country with a rapidly emerging pharmaceuticals and biotech (P&B) sector, and a history of using coordinated innovation and industrial policy for strategic and developmental ends. We investigate the extent to which 'government guidance funds' (GGFs), strategic industrial financing vehicles (a 'push' mechanism), support the development of antimicrobials as part of China's 'mission-driven' approach to innovation and industrial policy. GGFs are potentially globally significant, having raised approximately US$ 872 billion to 2020., Results: GGFs have a substantial role in P&B, but almost no role in developing new antimicrobials, despite this being a priority in the country's AMR National Action Plan. There are multiple constraints on GGFs' ability to function as part of a mission-driven approach to innovation at present, linked to their business model and the absence of standard markets for antimicrobials (or other effective 'pull' mechanisms), their unclear 'social' mandate, and limited technical capacity. However, GGFs are highly responsive to changing policy demands and can be used strategically by government in response to changing needs., Conclusions: Despite the very limited role of GGFs in developing new antimicrobials, their responsiveness to policy means they are likely to play a larger role as P&B becomes an increasingly important component of China's innovation and industrial strategy. However, for GGFs to effectively play that role, there is a need for reforms to their governance model, an increase in technical and managerial capacity, and supporting ('pull') incentives, particularly for pharmaceuticals such as antimicrobials for which there is strong social need, but a limited market. Given GGFs' scale and strategic importance, they deserve further research as China's P&B sector becomes increasingly globally important, and as the Chinese government commits to a larger role in global health., (© 2024. The Author(s).)

Background: In 2017, we published an article addressing drug shortages (DS) in Israel, exploring regulatory perspectives, challenges, and potential solutions. Since then, DS remain a significant concern for patients, healthcare providers, and policymakers globally. In this updated article, we revisit the topic, providing new insights, data, and analysis on the current DS landscape in Israel, efforts to mitigate them, and propose strategies to combat this escalating issue., Methods: We conducted a comprehensive search of the Israeli Ministry of Health (MOH) DS database, spanning from 2014 to the present. We extracted DS numbers and their reasons. Further searches on the Israeli MOH website, pharmaceutical division archives, and the internet yielded official MOH publications and correspondence regarding regulatory responses to DS from 2017 onwards. Additionally, two specific cases of DS were examined to analyze their handling. Recent activities and publications from the Israeli MOH aimed at reducing DS were also reviewed., Results: Between 2014 and 2022, DS surged 2.66-fold. Total DS were 3228; 672 due to commercial reasons, and 2556 to operational reasons (20.5% and 79.5% respectively). The average duration of intermittent DS increased 1.56-fold, from 85 to 133 days. Manufacturers informed the MOH 22 days prior to actual shortage on average. Analyzing 2022's DS (640) by ATC groups, prominent categories included nervous system drugs (18%), drugs acting on the alimentary tract and metabolism (14%), and dermatologicals (11%). Operational DS in 2022 (n = 564) were primarily due to stock delivery delays (38%), stock over-utilization (12%), and raw material shortages (9%). Sixteen official MOH publications on DS were identified from 2017 onwards. Moreover, two high-impact DS case studies were examined., Conclusion: Despite routine monitoring by the Israeli MOH and updating the DS policy throughout this period, DS persist, intensifying annually and posing serious health risks. This trend mirrors international patterns, affecting countries globally. In Israel's uniquely structured healthcare system, with its swift stakeholder cooperation and implementation capabilities, more effective DS management is conceivable. We propose ten universally applicable rules to address DS challenges., (© 2024. The Author(s).)

We report the successful fabrication of a pharmaceutical cellular bank (PCB) containing magnetotactic bacteria (MTB), which belong to the Magnetospirillum gryphiswaldense MSR1 species. To produce such PCB, we amplified MTB in a minimal growth medium essentially devoid of other heavy metals than iron and of CMR (Carcinogenic, mutagenic and reprotoxic) products. The PCB enabled to acclimate MTB to such minimal growth conditions and then to produce highly pure magnetosomes composed of more than 99.9% of iron. The qualification of the bank as a PCB relies first on a preserved identity of the MTB compared with the original strain, second on genetic bacterial stability observed over 100 generations or under cryo-preservation for 16 months, third on a high level of purity highlighted by an absence of contaminating microorganisms in the PCB. Furthermore, the PCB was prepared under high-cell load conditions (9.10 8  cells/mL), allowing large-scale bacterial amplification and magnetosome production. In the future, the PCB could therefore be considered for commercial as well as research orientated applications in nanomedicine. We describe for the first-time conditions for setting-up an effective pharmaceutical cellular bank preserving over time the ability of certain specific cells, i.e. Magnetospirillum gryphiswaldense MSR1 MTB, to produce nano-minerals, i.e. magnetosomes, within a pharmaceutical setting., (© 2024. The Author(s).)

Background: Over the last twenty years of orphan drug regulation in Europe, the regulatory framework has increased its complexity, with different regulatory paths and tools engineered to facilitate the innovation and accelerate approvals. Recently, the proposal of the new Pharmaceutical Legislation for the European Union, which will replace at least three Regulations and one Directive, was released and its new framework is raising many questions. The aim of this study was to present a characterisation of the Orphan Medicinal Products (OMPs) authorised by the European Commission (EC), between 2010 and 2022, looking into eighteen variables, contributing to the ongoing discussion on the proposal and implementation of the new Pharmaceutical Legislation proposed., Methods: Data of the OMPs identified and approved between 2010 and 2022 were extracted from the European Public Assessment Reports (EPARs) produced by the European Medicines Agency. Information regarding legal basis of the application, applicant, protocol assistance received, type of authorization, registration status, type of molecule, ATC code, therapeutic area, target age, disease prevalence, number of pivotal clinical trials supporting the application, clinical trial designs, respective efficacy endpoints and number of patients enrolled in the pivotal clinical trials were extracted. A descriptive statistical analysis was applied., Results: We identified 192 OMPs approved in the period between 2010 and 2022. 89% of the OMPs have legal basis of "full application". 86% of the sponsors received protocol assistance whereas 64% of the MAA benefited from the accelerated assessment. 53% of the active substances are small molecules; about 1 in 5 molecules are repurposed. 40% of the OMPs have oncological therapeutic indications and 56% of the OMPs are intended to treat only adults. 71% of the products were approved based on a single pivotal trial., Conclusions: This analysis of OMPs approved between 2010 and 2022 shows that a shift has occurred in the rare disease medicine development space. Through the period studied we observe an increase of non-small molecules approved, accelerated assessment received and non-standard MA's granted., (© 2024. The Author(s).)

Background: Individuals suffering with addiction have historically experienced disproportionally high levels of stigma. The process of inpatient care for those with substance abuse disorder (SUD) is multifaceted, shaped by the interplay of human interactions within the healthcare team and overarching structural factors like policy. While existing literature predominantly addresses personal and interpersonal stigma, the influence of structural stigma on care delivery practices remains understudied. Our research aims to investigate the impact of structural stigma on care processes for individuals with SUD admitted to acute medicine units., Methods: We conducted a secondary analysis of observation notes and interview transcripts utilizing an analytic framework related to structural stigma adapted from previous research. Data was collected from June 2019 to January 2020 in 2 hospitals. 81 participants consented to observation and 25 to interviews. Interviews were conducted with patients (n = 8), healthcare staff (n = 16), and caregivers (n = 1)., Results: Each aspect of care for people with SUD is adversely influenced by structural forms of stigma. There was evidence of a gap in accessing care and time pressures which deteriorated care processes. Structural stigma also manifested in the physical spaces designed for care and the lack of adequate resources available for mental health and addictions care. We found that structural stigma perpetuated other forms of implicit and explicit stigma., Conclusions: Structural stigma and other forms of stigma are interconnected. Improving care for people with SUD in hospital settings may require addressing structural forms of stigma such as how physical spaces are designed and how mental healthcare is integrated with physical healthcare within inpatient settings., (© 2024. The Author(s).)

Background: People who inject drugs (PWID) are at increased risk of HIV acquisition and often encounter barriers to accessing healthcare services. Uganda has high HIV prevalence among PWID and lacks integrated pre-exposure prophylaxis (PrEP) and harm reduction services. Understanding PWID experiences accessing and using harm reduction services and PrEP will inform strategies to optimize integration that align with PWID needs and priorities., Methods: Between May 2021 and March 2023, we conducted semi-structured interviews with PWID in Kampala, Uganda. We recruited participants with and without previous experience accessing harm reduction services and/or PrEP using purposive and snowball sampling. Interviews were audio recorded, translated, and transcribed. We used thematic analysis to characterize motivations for uptake of harm reduction and HIV prevention services, and strategies to optimize delivery of needle and syringe programs (NSP), medications for opioid use disorder (MOUD), and PrEP., Results: We conducted interviews with 41 PWID. Most participants were relatively aware of their personal HIV risk and accurately identified situations that increased risk, including sharing needles and engaging in transactional sex. Despite risk awareness, participants described engaging in known HIV risk behaviors to satisfy immediate drug use needs. All reported knowledge of harm reduction services, especially distribution of sterile needles and syringes, and many reported having experience with MOUD. Participants who had accessed MOUD followed two primary trajectories; limited resources and relationships with other PWID caused them to discontinue treatment while desire to regain something they believed was lost to their drug use motivated them to continue. Overall, PrEP knowledge among participants was limited and few reported ever taking PrEP. However, participants supported integrating PrEP into harm reduction service delivery and advocated for changes in how these services are accessed. Stigma experienced in healthcare facilities and challenges acquiring money for transportation presented barriers to accessing current facility-based harm reduction and HIV prevention services., Conclusions: Meeting the HIV prevention needs of PWID in Uganda will require lowering barriers to access, including integrated delivery of PrEP and harm reduction services and bringing services directly to communities. Additional training in providing patient-centered care for healthcare providers may improve uptake of facility-based services., (© 2024. The Author(s).)

Background: Financial interactions between pharmaceutical companies and physicians lead to conflicts of interest. This study examines the extent and trends of non-research payments made by pharmaceutical companies to board-certified allergists in Japan between 2016 and 2020., Methods: A retrospective analysis of disclosed payment data from pharmaceutical companies affiliated with the Japanese Pharmaceutical Manufacturers Association was conducted. The study focused on non-research payments for lecturing, consulting, and manuscript drafting made to board-certified allergists from 2016 to 2020. We performed descriptive analyses on payment data. Trends were analyzed using generalized estimating equation models., Results: Of the 3,943 board-certified allergists, 2,398 (60.8%) received non-research payments totaling $43.4 million over five years. Lecturing fees comprised 85.7% ($37.2 million) of the total payment amounts. For allergists who received at least one payment, the median amount per allergist was $3,106 (interquartile range: $966 - $12,124), in contrast to a mean of $18,092 (standard deviation: $49,233) over the five-year span. The top 1% and 10% of these allergists accounted for 20.8% and 68.8% of all non-research payments, respectively. The annual payment amounts significantly increased by 7.2% annual increase (95% CI: 4.4 - 10.0%, p < 0.001) each year until 2019, but saw a significant decrease in 2020 amid the COVID-19 pandemic., Conclusion: The majority of allergists received non-research payments, with a notable concentration among a small group. Payments increased annually until the pandemic's onset, which coincided with a substantial decrease. Further research is needed to explore the implications of these financial interactions on clinical practice and patient care in Japan., (© 2024. The Author(s).)

Background: ATDOM is the Catalan home healthcare program at primary care level. Patients in the home care program are usually frail, elderly people with multiple comorbidities. They are often polymedicated, leading to a high risk of drug-related problems (DRPs). Our hypothesis is that the pharmacist-led individualized review of the pharmacotherapeutic plans of ATDOM patients will be effective in improving the quality of treatments by reducing DRPs in terms of indication, adequacy, effectiveness, and safety., Methods: Aim: To compare the effectiveness of a standardized pharmaceutical intervention for the review and optimization of pharmacological treatments in ATDOM patients with usual management practice., Design: Pragmatic randomized clinical trial with a comparable control group, with prospective follow-up regarding the intervention on the adequacy of the pharmacological treatment of patients in the ATDOM program., Setting: Primary care teams in the Camp de Tarragona Primary Care Area, Tarragona, Spain., Participants: Four hundred and thirty-two ATDOM patients will be recruited, those who are over 65 years old and who are currently undergoing pharmacological treatment., Measures: Effectiveness of a six-month long intervention in reducing DRPs per patient and polypharmacy. Additionally, in the intervention group we will evaluate the implementation of the proposals for change or improvement made by the responsible physician., Analysis: The outcomes will be analyzed on an intent-to-treat basis and the analysis units will be the individual patients. Logistic regression and linear regression models will be used to evaluate the effects of the intervention on dichotomous and continuous variables versus the control arm., Ethics: The protocol was approved by the Research Ethics Committee of the Jordi Gol Primary Care Research Institute (IDIAPJGol), Barcelona, (19/141-P)., Discussion: If the results of the pharmaceutical intervention are favorable, widespread implementation of the program could be possible. It could be extended to all ATDOM patients or outpatients in general. Interdisciplinary teamwork could be strengthened as a result, which would improve the healthcare continuum., Trial Registration: Retrospectively registered., Clinicaltrials: gov Identifier NCT05820945; Registered 21 March, 2023., (© 2024. The Author(s).)

Introduction: Immediate access to naloxone is needed to prevent fatal opioid-related overdoses in the presence of fentanyl analogs saturating the opioid supply. Peer models engage impacted populations who are not accessing naloxone through standard venues, yet compensating peers who utilize syringe service programs with cash stipends to distribute naloxone within networks of people who use drugs is not well described., Methods: As part of the HEALing Communities Study, syringe service program-based interventions were developed in Holyoke and Gloucester, MA, which paid people who use drugs ("peers") cash to distribute naloxone. Early program outcomes were evaluated for the time each program was funded within the HCS study period., Results: During 22 study-months of observation, peers in two communities distributed 1104 naloxone kits. The total cost of peer compensation for program delivery was $10,510. The rate of peer-distributed naloxone per 100 K population reached 109 kits/mo and 222 kits/mo in the two communities. Participating peers addressed gaps in harm reduction outreach and distributed naloxone and other harm reduction equipment to individuals who were not syringe service program participants, expanding organizational reach. Being compensated with unrestricted cash stipends supported dignity and acknowledged peers' work in overdose prevention., Conclusion: The underutilization of compensated peer models is often attributed to funding and organizational barriers. These programs demonstrate that providing cash stipends to peers is feasible and expanded naloxone distribution at two existing syringe service programs. Providing cash stipends for peers who engage in secondary naloxone distribution offers promise in delivering naloxone to people not accessing syringe services., (© 2024. The Author(s).)

Background: Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, "whole-person" strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit ("mobile unit") with peer navigation compared to peer navigation alone to access these services at brick and mortar locations., Methods: HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of "one-stop" integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization., Discussion: This trial responds to a need for evidence on using a "whole-person" strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care., Trial Registration: ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021., (© 2024. The Author(s).)

Background: Despite the pivotal role of clinical trials in advancing orthopaedic oncology knowledge and treatment strategies, the persistent issues of trial discontinuation and nonpublication are significant problems. This study conducted an analysis examining clinical trial discontinuation rates, associations between intervention types and discontinuation/nonpublication, and the role of funding, enrollment size, and their implications for trial success and completion., Methods: This study, conducted on May 1, 2023, utilized a cross-sectional design to comprehensively analyze phase 3 and 4 randomized controlled trials within the realm of orthopaedic oncology. We specifically incorporated Phase 3 and 4 trials as they are designed to evaluate prolonged outcomes in human subjects and are more likely to reach publication. Study characteristics of interest included the intervention utilized in the clinical trial, presence of funding, whether the trial was published, completed, and trial enrollment size. The investigation involved an examination of ClinicalTrials.gov, a prominent online repository of clinical trial data managed by the National Library of Medicine of the USA. Descriptive statistics and multivariate logistic regressions were used to determine statistical significance., Results: Among the cohort of 130 trials, 19.2% were prematurely discontinued. Completion rates varied based on intervention type; 111 pharmaceutical trials demonstrated a completion rate of 83.8%, whereas 19 non-pharmaceutical trials exhibited a completion rate of 8.0% (P < .001). Surgical trials, totaling 10, showed a completion rate of 90%. The overall trial publication rate was 86.15%, with pharmaceutical interventions achieving a publication rate of 91.96%. Larger-scale trials (≥ 261 participants) emerged as a protective factor against both discontinuation (Adjusted Odds Ratio [AOR]: 0.85, 95% Confidence Interval [CI] 0.42-0.95) and nonpublication (AOR: 0.19, 95% CI 0.13-.47), compared to smaller-scale trials., Conclusion: This study accentuates the heightened vulnerability of non-pharmaceutical interventions and trials exhibiting lower rates of enrollment to the issues of discontinuation and nonpublication. Moving forward, the advancement of clinical trials necessitates a concerted effort to enhance trial methodologies, especially concerning nonpharmaceutical interventions, along with a meticulous refinement of participant enrollment criteria., (© 2024. The Author(s).)

Background: People who use drugs (PWUD) experience elevated HIV risk and numerous barriers to facility-based HIV testing. HIV self-testing (HIVST) could circumvent many of those barriers and is acceptable among PWUD, yet HIVST implementation for PWUD is limited. Service providers' perspectives on specific HIVST delivery strategies could help increase availability for PWUD., Methods: From April-November 2021, we interviewed 16 health, harm reduction, and social service providers working with PWUD in San Diego, CA. Interviews and rapid thematic analysis explored perspectives on HIVST's utility and appropriateness, as well as the feasibility of and anticipated challenges with specific HIVST delivery strategies, including peer or secondary distribution., Results: Participants viewed HIV as a significant threat to PWUD health and confirmed the presence of numerous barriers to local facility-based HIV testing. Participants viewed HIVST as a promising and potentially empowering solution. Based on community familiarity with secondary distribution of harm reduction supplies (i.e., naloxone) and information, participants viewed secondary distribution of HIVST kits as an appropriate and feasible strategy for increasing the reach of HIVST, but also described potential barriers (e.g., engaging socially disconnected individuals, ensuring linkages to services following HIVST) and provided suggestions for alternative HIVST kit delivery models (e.g., harm reduction vending machines)., Conclusions: Service providers viewed secondary distribution of HIVST kits among PWUD as promising, appropriate, and feasible, yet specialized efforts may be needed to reach the most marginalized individuals and ensure consistent provision of educational information and referral supports that maximize the impact of this approach., (© 2024. The Author(s).)

Background: Globally, an estimated 14% of adults live with migraine disease which impacts their physical, emotional and social wellbeing. To target the disease comprehensively, research recommends a multidisciplinary approach to migraine management. Yet, at present, migraine management primarily centers around pharmaceutical treatments. The aim of this study was to investigate the extent to which emotional awareness could influence the uptake of self-care behaviours of community-dwelling adults with migraine., Methods: A cross-sectional online survey explored personal experiences with migraine disease and strategies or behaviours to manage migraine attacks. Chi-squared tests were used to investigate differences in ratings of migraine prevention and management strategies between users and non-users of the strategies. Univariable logistic regressions were used to assess the effectiveness of self-care behaviours to manage or prevent migraine attacks., Results: We surveyed 170 community-dwelling adults with migraine in the United Kingdom, Austria, Germany and the United States. Most (85%) respondents had experienced migraine for over five years, where 42% of attacks usually lasted several days. Whereas we did not differentiate between diagnosis by a neurologist or self-diagnosis, the most common diagnoses in the cohort were migraine without aura (38.9%) and migraine with aura (29%). Staying hydrated was the most popular preventative strategy (87%), 70.2% used prescription medication and 64.9% changed their diet and/or supplements. Almost all ( 92.4%) respondents stated that their mood or emotions could trigger their migraine attacks. Keeping a headache or mood diary was the lowest-rated prevention strategy and was rated as "probably ineffective" or causing "no change" in preventing migraine attacks. Over a third (39.7%) kept track of their physical wellbeing and symptoms. Reasons stated for tracking symptoms included to identify triggers (65.8%), show reports to a healthcare professional (59.6%), understand when they must take medication (48.1%), track improvements (67.3%) or deteriorations (67.3%)., Conclusions: Migraine management is dominated by pharmaceutical management for acute pain attacks and lifestyle changes for managing migraine long-term. Perception of the effectiveness of those techniques is high, whereas perception of interventions that target the emotional or psychological components of chronic pain management (keeping a mood diary, and mental health support) is mixed. There exists a gap between the recommended biopsychosocial approach and the current state of migraine management., (© 2024. The Author(s).)

Background: Osteosarcoma represents a serious clinical challenge due to its widespread genomic alterations, tendency for drug resistance and distant metastasis. New treatment methods are urgently needed to address those treatment difficulties in osteosarcoma to improve patient prognoses. In recent years, small-molecule based anion transporter have emerged as innovative and promising therapeutic compound with various biomedical applications. However, due to a lack of efficient delivery methods, using ion transporters as therapeutic drugs in vivo remains a major challenge., Result: Herein, we developed self-assembled supramolecular drugs based on small-molecule anion transporters, which exhibited potent therapeutic effect towards osteosarcoma both in vitro and in vivo. The anion transporters can disrupt intracellular ion homeostasis, inhibit proliferation, migration, epithelial-mesenchymal transition process, and lead to osteosarcoma cell death. RNA sequencing, western blot and flow cytometry indicated reprogramming of HOS cells and induced cell death through multiple pathways. These pathways included activation of endoplasmic reticulum stress, autophagy, apoptosis and cell cycle arrest, which avoided the development of drug resistance in osteosarcoma cells. Functionalized with osteosarcoma targeting peptide, the assembled supramolecular drug showed excellent targeted anticancer therapy against subcutaneous xenograft tumor and lung metastasis models. Besides good tumor targeting capability and anti-drug resistance, the efficacy of the assembly was also attributed to its ability to regulate the tumor immune microenvironment in vivo., Conclusions: In summary, we have demonstrated for the first time that small-molecule anion transporters are capable of killing osteosarcoma cells through multiple pathways. The assemblies, OTP-BP-L, show excellent targeting and therapeutic effect towards osteosarcoma tumors. Furthermore, the supramolecular drug shows a strong ability to regulate the tumor immune microenvironment in vivo. This work not only demonstrated the biomedical value of small-molecule anion transporters in vivo, but also provided an innovative approach for the treatment of osteosarcoma., (© 2024. The Author(s).)

Background: Characterizing the diffusion of adopted changes in policy and clinical practice can inform enhanced implementation strategies to ensure prompt uptake in public health emergencies and other rapidly evolving disease areas. A novel guidance document was introduced at the onset of the COVID-19 pandemic in British Columbia (BC), Canada, which supported clinicians to prescribe opioids, stimulants, and benzodiazepines. We aimed to determine the extent to which uptake and discontinuation of an initial attempt at a prescribed safer supply (PSS) program were influenced through networks of prescribers., Methods: We executed a retrospective population-based study using linked health administrative data that captured all clinicians who prescribed to at least one client with a substance use disorder from March 27, 2020, to August 31, 2021. Our main exposure was the prescribing patterns of an individuals' peers, defined as the proportion of a prescribers' professional network (based on shared clients), which had previously prescribed PSS, updated monthly. The primary outcome measured whether a clinician had prescribed their initial PSS prescription during a given calendar month. The secondary outcome was the discontinuation of PSS prescribing, defined as an absence for PSS prescriptions for at least 3 months. We estimated logistic regression models using generalized estimated equations on monthly repeated measurements to determine and characterize the extent to which peer networks influenced the initiation and discontinuation of PSS prescribing, controlling for network, clinician, and caseload characteristics. Innovators were defined as individuals initiating PSS prior to May 2020, and early adopters were individuals initiating PSS after., Results: Among 14,137 prescribers treating clients with substance use disorder, there were 228 innovators of prescribed safer supply and 1062 early adopters through the end of study follow-up, but 653 (50.6%) were no longer prescribing by August 2021. Prescribers with over 20% of peers whom had adopted PSS had a nearly fourfold higher adjusted odds of PSS prescribing themselves (aOR: 3.79, 95% CI: (3.15, 4.56)), compared to those with no connected safer supply prescribers., Conclusions: The uptake of PSS in BC was highly dependent on the behavior of prescribers' peer networks. Future implementation strategies to support PSS or other policies would benefit from leveraging networks of prescribers., (© 2024. The Author(s).)

Local medical systems (LMSs) are complex and dynamic, encompassing local perceptions of diseases, prevention and treatment strategies, and evaluations of therapeutic responses. These systems are not isolated and interact with other medical systems, such as the biomedical system. The interaction between these systems creates a "contact zone", which some authors refer to as intermedicality, involving both competitive and complementary interactions. However, there is limited discussion in the literature regarding the complexity of these interactions. Some studies seek to understand this interaction through the lens of hybridization, a concept introduced to ethnobiology by Ana Ladio and Ulysses Albuquerque. The authors conceptualize hybridization as "discrete structures and practices coming together to form a new practice not necessarily implying homogenization." They discuss hybridization in the context of medicinal plants used in urban settings and propose seven hybridization subprocesses to gain a deeper understanding of this phenomenon. In this study, we update these hybridization subprocesses, expanding the concepts to comprehend the specific interaction of resources from LMS and biomedical systems known and used by different human groups. In this context, we propose a new subprocess and have made adjustments to the existing subprocesses to encompass the diversity of possible interactions between medicinal plants and pharmaceuticals, providing evidence from the literature demonstrating interactions that can be classified within the proposed subprocesses. Furthermore, we discuss, from a theoretical standpoint, how these subprocesses may have implications for the resilience of medical systems. Moreover, we propose a flowchart that can be utilized to identify these hybridization subprocesses in intermedicality contexts in future studies. These classifications are crucial because they enable us to comprehend the complexity of interactions between medicinal plants and pharmaceuticals, as well as the impacts that these different interactions can have on the resilience of LMSs., (© 2023. The Author(s).)

Background: Discarding pharmaceuticals in the garbage or into the sewage system are still the most common methods in many countries. This study aims to investigate the guidance provided by pharmacists to customers on the disposal of unused and expired household medications in São Paulo State, Brazil., Method: The study population consisted of 630 pharmacists from the State of São Paulo, who work in community pharmacies. They answered an online questionnaire with questions composed in three blocks: demographic, work, and academic information on the pharmacist; guidance about the disposal of household medications; and knowledge regarding the reverse logistics of these medications. An invitation to participate in the questionnaire was made via WhatsApp, individually and collectively. Inferential statistics were performed using the chi-square test and were considered significant when p < 0.05%., Results: Among the participating pharmacists, the majority were women under 60 years old,56 (8.89%) stated that they never orient the customer regarding the disposal of unused and expired household medications, while 574 (91,12%) indicated that they almost provide guidance. The frequency with which they provided guidance was influenced by the number of years since graduation (p = 0.0047), the time they had worked in pharmacies and drugstores (p = 0.0007), and whether or not they had a graduate degree (p = 0.0181). Regarding the disposal of medications, among the 643 responses provided by the pharmacists,516 (80.25%) indicated that they oriented customers to return them to a pharmacy., Conclusion: A small number of pharmacists always orient customers on the proper disposal that should be followed for unused and expired household medications, prioritizing their return to a pharmacy. In general, these pharmacists have longer periods of work experience and higher academic qualifications. Thus, it is important to increase knowledge through professional training and further education programs., (© 2023. The Author(s).)

Background: The frass of several herbivorous insect species has been utilised as natural medicines in Asia; however, the metabolite makeup and pharmaceutical activities of insect frass have yet to be investigated. Oligophagous Papilionidae insects utilise specific kinds of plants, and it has been suggested that the biochemicals from the plants may be metabolised by cytochrome P450 (CYP) in Papilionidae insects. In this study, we extracted the components of the frass of Papilio machaon larvae reared on Angelica keiskei, Oenanthe javanica or Foeniculum vulgare and examined the biological activity of each component. Then, we explored the expression of CYP genes in the midgut of P. machaon larvae and predicted the characteristics of their metabolic system., Results: The components that were extracted using hexane, chloroform or methanol were biochemically different between larval frass and the host plants on which the larvae had fed. Furthermore, a fraction obtained from the chloroform extract from frass of A. keiskei-fed larvae specifically inhibited the cell proliferation of the human colon cancer cell line HCT116, whereas fractions obtained from the chloroform extracts of O. javanica- or F. vulgare-fed larval frass did not affect HCT116 cell viability. The metabolites from the chloroform extract from frass of A. keiskei-fed larvae prevented cell proliferation and induced apoptosis in HCT116 cells. Next, we explored the metabolic enzyme candidates in A. keiskei-fed larvae by RNA-seq analysis. We found that the A. keiskei-fed larval midgut might have different characteristics from the O. javanica- or F. vulgare-fed larval metabolic systems, and we found that the CYP6B2 transcript was highly expressed in the A. keiskei-fed larval midgut., Conclusions: These findings indicate that P. machaon metabolites might be useful as pharmaceutical agents against human colon cancer subtypes. Importantly, our findings show that it might be possible to use insect metabolic enzymes for the chemical structural conversion of plant-derived compounds with complex structures., (© 2023. The Author(s).)

Lower extremity deep venous thrombosis (LEDVT) affects patient's quality of life for a long time, and even causes pulmonary embolism, which threatens human health. Current anticoagulant drugs in clinical treatment are hampered by the risk of bleeding due to poor targeting and low drug penetration. Here, we used platelet (PLT)-like biological targeting to enhance the delivery and accumulation of nanomedicines in thrombus and reduce the risk of bleeding. Meanwhile, the parallel strategy of "thrombus thermal ablation and anticoagulation" was applied to increase the permeability of drugs in thrombus and achieve the optimal antithrombotic effect. Polypyrrole (PPy) and rivaroxban (Riv, an anticoagulant drug) were co-assembled into platelet membrane-coated nanoparticles (NPs), PLT-PPy/Riv NPs, which actively targeted the thrombotic lesion at multiple targets in the platelet membrane and were thermally and drug-specific thrombolysed by 808 nm laser irradiation. The combination therapy resulted in up to 90% thrombolysis in a femoral vein thrombosis model compared to single phototherapy or drug therapy. The results showed that the nanoformulation provided a new direction for remote precise and controlled sustained thrombolysis, which was in line with the trend of nanomedicine towards clinical translation., (© 2023. The Author(s).)

Background: High-grade serous ovarian cancer (OvCa) is the most common type of epithelial OvCa. It is usually diagnosed in advanced stages, leaving a woman's chance of survival below 50%. Despite traditional chemotherapeutic therapies, there is often a high recurrence rate following initial treatments. Hence, a targeted drug delivery system is needed to attack the cancer cells and induce apoptosis, overcome acquired drug resistance, and protect normal cells from cytotoxicity. The present study shows that targeting folate receptor alpha (FRα) through planetary ball milling (PBM) nanoparticles (NPs) induces apoptosis in OvCa cells., Results: Human tissue microarrays (TMAs) show overexpression of FRα in Stage IV OvCa tissues compared to matched normal tissues. They provide a focus for a targeted delivery system. We formulated PBM nanoparticles encapsulated with paclitaxel (PTX) or fisetin (Fis) and conjugated with folic acid (FA). The cytotoxic effect of these PBM NPs reduced the concentration of the toxic chemotherapy drug PTX by five-fold. The combined treatment of PTX-FA NPs and Fis-FA NPs inhibited cell proliferation and induced apoptosis more extensively than the individual drugs alone. Apoptosis of OvCa cells, determined by flow cytometry, showed an increase from 14.4 to 80.4% (OVCAR3 cells) and from 2.69 to 90.0% (CAOV3 cells) in the number of apoptotic cells. Also, expressions of the pro-apoptotic markers, BAK and active caspase-3, were increased after PTX-FA + Fis-FA PBM NP treatment. In addition to looking at targeted treatment effects on apoptosis, drug resistance was investigated. Drug resistance in OvCa cells was reversed by ABCG2, an ABC-transporter marker., Conclusions: Our study shows that PTX-FA and Fis-FA PBM NPs directly target platinum-resistant OvCa cells, induce cytotoxic/apoptotic effects, and reverse multi-drug resistance (MDR). These findings allow us to create new clinical applications using PTX-FA and Fis-FA combination nanoparticles to treat drug-resistant cancers., (© 2023. The Author(s).)

Background: (Hydroxy)cinnamyl alcohols and allylphenols, including coniferyl alcohol and eugenol, are naturally occurring aromatic compounds widely utilised in pharmaceuticals, flavours, and fragrances. Traditionally, the heterologous biosynthesis of (hydroxy)cinnamyl alcohols from (hydroxy)cinnamic acids involved CoA-dependent activation of the substrate. However, a recently explored alternative pathway involving carboxylic acid reductase (CAR) has proven efficient in generating the (hydroxy)cinnamyl aldehyde intermediate without the need for CoA activation. In this study, we investigated the application of the CAR pathway for whole-cell bioconversion of a range of (hydroxy)cinnamic acids into their corresponding (hydroxy)cinnamyl alcohols. Furthermore, we sought to extend the pathway to enable the production of a variety of allylphenols and allylbenzene., Results: By screening the activity of several heterologously expressed enzymes in crude cell lysates, we identified the combination of Segniliparus rugosus CAR (SrCAR) and Medicago sativa cinnamyl alcohol dehydrogenase (MsCAD2) as the most efficient enzymatic cascade for the two-step reduction of ferulic acid to coniferyl alcohol. To optimise the whole-cell bioconversion in Escherichia coli, we implemented a combinatorial approach to balance the gene expression levels of SrCAR and MsCAD2. This optimisation resulted in a coniferyl alcohol yield of almost 100%. Furthermore, we extended the pathway by incorporating coniferyl alcohol acyltransferase and eugenol synthase, which allowed for the production of eugenol with a titre of up to 1.61 mM (264 mg/L) from 3 mM ferulic acid. This improvement in titre surpasses previous achievements in the field employing a CoA-dependent coniferyl alcohol biosynthesis pathway. Our study not only demonstrated the successful utilisation of the CAR pathway for the biosynthesis of diverse (hydroxy)cinnamyl alcohols, such as p-coumaryl alcohol, caffeyl alcohol, cinnamyl alcohol, and sinapyl alcohol, from their corresponding (hydroxy)cinnamic acid precursors but also extended the pathway to produce allylphenols, including chavicol, hydroxychavicol, and methoxyeugenol. Notably, the microbial production of methoxyeugenol from sinapic acid represents a novel achievement., Conclusion: The combination of SrCAR and MsCAD2 enzymes offers an efficient enzymatic cascade for the production of a wide array of (hydroxy)cinnamyl alcohols and, ultimately, allylphenols from their respective (hydroxy)cinnamic acids. This expands the range of value-added molecules that can be generated using microbial cell factories and creates new possibilities for applications in industries such as pharmaceuticals, flavours, and fragrances. These findings underscore the versatility of the CAR pathway, emphasising its potential in various biotechnological applications., (© 2023. The Author(s).)

Introduction: The COVID-19 pandemic is a serious threat to everyone's health. Numerous studies have demonstrated that vaccines are very effective in preventing COVID-19-related severe illness, hospitalization, and death. Children's vaccination exerts its protecting effect by preventing the spread of the virus. The purpose of this study was to analyze the rate of COVID-19 immunization among Lebanese children aged 1 to 11 years and assess parental factors that affect immunization rates., Methods: An online cross-sectional study was conducted between January and March 2023. The online survey was distributed across all social media channels, including the Ministry of Public Health website., Results: A total of 390 parents filled the survey (mean age = 37.48 ± 8.39 years; 50.5% mothers; 70% with a university level of education). Mothers compared to fathers, having a history of bad reaction to a vaccine vs. not, and higher vaccine hesitancy were significantly associated with less willingness to administer the vaccine to the child. Trusting pharmaceutical companies was significantly associated with more willingness to administer the vaccine to the child., Conclusion: The results of this study show that the factors associated with parents' decisions to vaccinate their children may vary. Our findings conclude that vaccine acceptance is being highly associated with parental concerns, trust, and information regarding the vaccine safety and efficacy., (© 2023. The Author(s).)

Background: Patient safety is a central healthcare policy worldwide. Adverse drug events (ADE) are among the main threats to patient safety. Children are at a higher risk of ADE in each stage of medication management process. ADE rate is high in the administration stage, as the final stage of preventing medication errors in pediatrics and neonates. The most effective way to reduce ADE rate is using medication administration clinical decision support systems (MACDSSs). The present study reviewed the literature on MACDSS for neonates and pediatrics. It identified and classified the data elements that mapped onto the Fast Healthcare Interoperability Resources (FHIR) standard and the functionalities of these systems to guide future research., Methods: PubMed/ MEDLINE, Embase, CINAHL, and ProQuest databases were searched from 1995 to June 31, 2021. Studies that addressed developing or applying medication administration software for neonates and pediatrics were included. Two authors reviewed the titles, abstracts, and full texts. The quality of eligible studies was assessed based on the level of evidence. The extracted data elements were mapped onto the FHIR standard., Results: In the initial search, 4,856 papers were identified. After removing duplicates, 3,761 titles, and abstracts were screened. Finally, 56 full-text papers remained for evaluation. The full-text review of papers led to the retention of 10 papers which met the eligibility criteria. In addition, two papers from the reference lists were included. A total number of 12 papers were included for analysis. Six papers were categorized as high-level evidence. Only three papers evaluated their systems in a real environment. A variety of data elements and functionalities could be observed. Overall, 84 unique data elements were extracted from the included papers. The analysis of reported functionalities showed that 18 functionalities were implemented in these systems., Conclusion: Identifying the data elements and functionalities as a roadmap by developers can significantly improve MACDSS performance. Though many CDSSs have been developed for different medication processes in neonates and pediatrics, few have actually evaluated MACDSSs in reality. Therefore, further research is needed on the application and evaluation of MACDSSs in the real environment., Protocol Registration: (dx.doi.org/10.17504/protocols.io.bwbwpape)., (© 2023. The Author(s).)

As a well-known group of the probiotic family, the Lactobacillus has increasingly contributed to hindering the growth of pathogens, particularly resistant species, in the last decades. Since antibiotic resistance has become a severe problem in global healthcare systems and considerably increased the mortality and morbidity rate in infectious diseases, we aimed to obtain a new stable formulation of Lactobacillus to overcome resistant infections. For this purpose, we designed various gel formulations containing Lactobacillus rhamnosus (L. rhamnosus) as an active pharmaceutical ingredient (API) in a water base and oil base gel, evaluated the probiotic stability in formulation to obtain an optimum formulation, and finally, investigated the antibacterial activities of that against two common hospital-associated multidrug-resistant pathogens, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Furthermore, the pharmaceutical aspects of the optimum formulation, including stability, homogeneity, spreadability, pH value, conductivity, and rheological behavior, were assessed.The results indicated that the optimum formulation based on glycerol exhibited desirable pharmaceutical properties, including long-term stability, a perfect level of homogeneity, an acceptable range of spreadability with pseudo-plastic thixotropic behavior, and a promising antibacterial potential against MRSA and VRE. Our findings indicate that this novel probiotic formulation could be an excellent candidate to cope with antibiotic-resistant species, representing a hopeful treatment potential for topical applications, particularly in incurable infections. However, further in vivo studies seem warranted to evaluate their bactericidal activity against multi-drug resistant microorganisms., (© 2023. The Author(s).)

Background: We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept., Methods: Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables., Results: The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product., Conclusions: Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory., Trial Registration: ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05., (© 2023. The Author(s).)

Background: The COVID-19 pandemic strained healthcare systems immensely as of 2020. Switzerland's hospital pharmacies' responses during the first wave were surveyed with a view to improving the quality of pharmaceutical management in future health crises., Methods: An online survey was sent to the heads of all of Switzerland's hospital pharmacies. The questionnaire was organised into eleven sections of questions covering many topics regarding the management of COVID-19's first wave. Data collection occurred from May to June 2020., Results: Analyses were performed using the 43 questionnaires (66%), with at least one answer per questionnaire, out of 65 distributed. Seventeen of 41 pharmacies responding (41%) had existing standard operating procedures or pandemic plans and 95% of these (39/41) set up crisis management steering committees. Twenty-nine of 43 pharmacies responding (67%) created new activities to respond to the pandemic's specific needs. Twenty-six of 39 pharmacies responding (67%) created new drug lists for: COVID-19-specific treatments (85%; 22/26), sedatives (81%; 21/26), anaesthetics (77%; 20/26) and antibiotics (73%; 19/26). Drug availability in designated COVID-19 wards was managed by increasing existing stocks (54%; 22/41 pharmacies) and creating extra storage space (51%; 21/41). Two drugs generated the greatest concern about shortages: propofol (49%; 19/39 pharmacies) and midazolam (44%; 17/39). Remdesivir stocks ran out in 26% of pharmacies (10/39). Twelve of 43 pharmacies (28%) drafted specific new documents to respond to medical needs regarding drug administration, 12 (28%) did so for drug preparation and 10 (23%) did so for treatment choices., Conclusions: Switzerland's hospital pharmacies encountered many challenges related to the COVID-19 crisis and had to find solutions quickly, effectively and safely. The survey highlighted the key role that hospital pharmacies played in many aspects of the pandemic by providing logistical and clinical support to medical and nursing care teams. The lessons and experiences outlined could be used to improve the quality of hospital pharmacies' readiness for similar future events., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Effective pharmaceutical inventory management is essential for optimizing healthcare outcomes and supply chain performance. However, challenges such as stockouts, overstocking, and wastage can hinder this process. This study examines the interrelationships between overstocking, stockouts, and wastage in eight healthcare facilities in Northern KwaZulu-Natal, South Africa. It also explores the extent of these challenges and investigates the use of medicine redistribution as a strategy to address inventory management issues., Methods: A retrospective quantitative analysis was conducted using pharmacy inventory records from public healthcare facilities. Eight facilities, including hospitals and a community healthcare center in King Cetshwayo District, were purposively sampled. Linear regression analysis was used to examine the association between medicine redistribution as the outcome and the predictors - stockouts, overstocking, and wastage. Pearson's correlation was utilized to evaluate associations between the predictors. Descriptive statistics were employed to quantify the levels and extent of overstocking, stockouts, and wastage related to expiry., Results: The study included eight healthcare facilities with pharmacy warehouses managed by pharmacists. A total of 392 medicines were analyzed (49 per facility). Stockouts affected 85.6% of medicines, while overstocking and expiry-related wastage impacted 50.6% and 15.2% of medicines, respectively. The most common stock-out medicines were salbutamol 200mcg inhalant (4.0%), paracetamol 500 mg tablets (3.5%), and azithromycin 500 mg tablets (3.3%). Overstocking, stock with short-dated expiry, and expired medicines explained 68% of redistribution transactions to other facilities (r² = 0.68). A moderate, statistically significant correlation was observed between overstocking and expiry-related wastage (r² = 0.47, p-value = 0.020). Stockouts had a weak correlation with redistribution, accounting for only 4.5% (p-value < 0.01). A weak correlation was found between stockouts and overstocking (r = 0.10), as well as between stockouts and expired medicines (r = -0.20)., Conclusion: This study highlights significant challenges in inventory management, particularly regarding stockouts, overstocking, and expiry-related wastage in the evaluated healthcare facilities. Medicine redistribution emerged as a viable strategy to address these challenges. Improving inventory management practices and implementing targeted interventions are crucial for optimizing pharmaceutical supply chain performance and enhancing healthcare delivery outcomes in this setting., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The impact of cancer interventions has been conducted in several research due to the significant burden of this non-communicable disease. The interventions that played an important role in the improvement of the patient's quality of life (QoL) and health-related quality of life (HRQL) can be classified into two main groups: pharmaceutical and non-pharmacological methods. However, studies so far often analyze a specific group of interventions for specific types of cancer. Thus, in this systematic review and meta-analysis, we synthesized the overall impact of cancer interventions on patients' quality of life in several cancers.In this research, we followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) to search the longitudinal original research on the Web of Science (WOS) database. After that, the Newcastle-Ottawa Scale (NOS) and Jadad Scale were used to assess the quality of non-randomized control trials and randomized control trials, respectively. Then, the characteristics of the included studies were described in the six main fields table and the random effect model with robust estimation was applied to analyze the impact of interventions on the health utility of patients.From the database, 122 longitudinal original research were included in the meta-regression, with most of them having high or fair quality. The European Organization for the research and treatment of cancer scale for quality of life (EORTC-QLQ) was the most used health utility measurement at 65.15%. In the adjusted effect models, the Visual Analogue Scale (VAS) had significant statistics in all models when we compared it with the EQ-5D Scale (p < 0.05) and several types of cancer such as breast, lung, and prostate cancer had significant statistics when comparing with hematological cancer in the model types of cancer (p < 0.01). Moreover, radiotherapy, screening, and a combination of chemotherapy and best supportive care also had significant statistics (p < 0.01) in the model of interventions when compared with radiotherapy applied only. Our research can suggest a vital combination of both pharmaceutical and non-pharmacological interventions to improve the quality of life of some common types of cancer patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Antibody technology is widely used in the fields of biomedical and clinical therapies. Nonetheless, the complex in vitro expression of recombinant proteins, long production cycles, and harsh storage conditions have limited their applications in medicine, especially in clinical therapies. Recently, this dilemma has been overcome to a certain extent by the development of mRNA delivery systems, in which antibody-encoding mRNAs are enclosed in nanomaterials and delivered to the body. On entering the cytoplasm, the mRNAs immediately bind to ribosomes and undergo translation and post-translational modifications. This process produces monoclonal or bispecific antibodies that act directly on the patient. Additionally, it eliminates the cumbersome process of in vitro protein expression and extends the half-life of short-lived proteins, which significantly reduces the cost and duration of antibody production. This review focuses on the benefits and drawbacks of mRNA antibodies compared with the traditional in vitro expressed antibodies. In addition, it elucidates the progress of mRNA antibodies in the prevention of infectious diseases and oncology therapy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Evidence of drug-induced liver injury is abundant in adults but is lacking in children. Our aim was to identify suspected drug signals associated with pediatric liver injury., Methods: Hepatic adverse events (HAEs) among children reported in the Food and Drug Administration Adverse Event Reporting System were analyzed. A descriptive analysis was performed to summarize pediatric HAEs, and a disproportionality analysis was conducted by evaluating reporting odds ratios (RORs) and proportional reporting ratios to detect suspected drugs., Results: Here, 14,143 pediatric cases were reported, specifically 49.6% in males, 45.1% in females, and 5.2% unknown. Most patients (68.8%) were 6-18 years old. Hospitalization ranked first among definite outcomes (7,207 cases, 37.2%). In total, 264 disproportionate drug signals were identified. The top 10 drugs by the number of reports were paracetamol (1,365; ROR, 3.6; 95% confidence interval (CI), 3.4-3.8), methotrexate (878; ROR, 2.5; 95% CI, 2.3-2.7), vincristine (649; ROR, 3.0; 95% CI, 2.8-3.3), valproic acid (511; ROR, 3.2; 95% CI, 2.9-3.6), cyclophosphamide (490; ROR, 2.4; 95% CI, 2.2-2.6), tacrolimus (427; ROR, 2.4; 95% CI, 2.2-2.7), prednisone (416; ROR, 2.1; 95% CI, 1.9-2.3), prednisolone (401; ROR, 2.3; 95% CI, 2.1-2.5), etoposide (378; ROR, 2.3; 95% CI, 2.1-2.6), and cytarabine (344; ROR, 2.8; 95% CI, 2.5-3.2). After excluding validated hepatotoxic drugs, six were newly detected, specifically acetylcysteine, thiopental, temazepam, nefopam, primaquine, and pyrimethamine., Conclusions: The hepatotoxic risk associated with 264 signals needs to be noted in practice. The causality of hepatotoxicity and mechanism among new signals should be verified with preclinical and clinical studies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The improper disposal of pharmaceutical preparations substantially threatens human health and environmental safety. Pharmacists are responsible for properly disposing of unwanted medications and educating patients about how to do so themselves. This study aimed to assess community pharmacists' knowledge, determine their views on how to dispose of unwanted pharmaceuticals, and assess the extent to which they realize that it is their responsibility to guide patients toward the safe disposal of expired medications., Methods: A descriptive cross-sectional study was conducted between December 2021 and April 2022 among 400 practicing pharmacists who were chosen to participate by random cluster sampling. Community pharmacists' practices, awareness, and beliefs about disposing of unused drugs were evaluated. The Statistical Package for Social Sciences (IBM-SPSS) version 21 was used for data entry and analysis., Results: Of 400 pharmacists, 348 stated that they did not participate in courses on the safe disposal of unwanted medications. Disposal of drugs in the garbage, an unsafe method, was very frequently recommended by pharmacists to patients, especially regarding inhalers, antibiotics, hormonal drugs, and solid and semisolid drugs. However, many pharmacists advised patients to return their hormonal, category B, and category C drugs to the pharmacy. A total of 61.3% of pharmacists agreed and 26% strongly agreed that unsafe disposal of drugs negatively affects the environment. A total of 54.3% of the participants agreed that improper disposal of antibiotics might be a reason for increased antimicrobial resistance, and 54.5% of them agreed that improper disposal of hormonal drugs might contribute to the development of certain cancers. A total of 80.3% of the participants perceived that most unwanted drugs in pharmacies were those returned from patients. A total of 97.3% of the participants supported establishing a drug disposal system, with 77.5% choosing to have the district health board responsible for funding this system. A total of 48.5% of the participants indicated that a lack of education and awareness on the issue of getting rid of unused drugs constitutes a challenge to the safe disposal of medicines, and 66% of them said that a lack of law enforcement constitutes another challenge. A total of 95.5% of the participants agreed or strongly agreed that good training for health sector workers and organizing workshops to develop knowledge on this subject would improve practices. A total of 93.3% supported distributing educational brochures, and 92.8% supported placing special containers in every pharmacy to collect unwanted drugs., Conclusions: Most pharmacists in our study returned drugs to manufacturing companies and stores, and few followed the correct methods of incineration and return of drugs to the Ministry of Health. Current data emphasize the issue of improper disposal of medicine in Palestine and the need for improved education among healthcare workers., (© 2023. The Author(s).)

Background: This study describes the effectiveness of a novel active pharmaceutical ingredient, fluralaner (isoxazoline class), against important ectoparasites infesting cattle in Brazil., Methods: A total of 13 studies involving a 5% fluralaner-based pour-on formulation (Exzolt 5%; further referred to as Exzolt) were conducted. Specifically, the effectiveness of this formulation was studied against Rhipicephalus microplus (6 studies), Cochliomyia hominivorax larvae (4 studies), Dermatobia hominis larvae (1 study) and Haematobia irritans flies (2 studies)., Results: The therapeutic efficacy of Exzolt was found to exceed 98% at 4 days post treatment (DPT), while persistent efficacy (> 90% efficacy) against repeated infestations of R. microplus was observed for up to 79 DPT. In field studies, ≥ 98% therapeutic efficacy was demonstrated at all study sites by 7 DPT, and a persistent efficacy (> 90% efficacy) was observed for 42, 49 or 56 DPT. Exzolt prevented C. hominivorax eggs from developing to the larval stage, thus mitigating the development of myiasis in cattle naturally and artificially infested with this screworm. The efficacy of Exzolt against D. hominis larvae was 98% at 3 DPT, while persistent efficacy (> 90% effectiveness) was found to last for up to 70 DPT. Against H. irritans, Exzolt showed therapeutic efficacy (≥ 90%) within the first day of treatment at both study sites, while persistent efficacy (≥ 90%) was observed for 7 DPT at one site and for 21 DPT at the other site., Conclusions: Overall, the results from these studies confirm that Exzolt is therapeutically efficacious against the most important ectoparasites infesting cattle in Brazil. The novel active pharmaceutical ingredient, fluralaner, provides a new treatment option for farmers to control cattle ectoparasites, especially where there is resistance to other chemical classes. In addition, an effective control of ectoparasites will improve overall cattle health and well-being as well as production., (© 2023. The Author(s).)

Background: Emergence of Plasmodium falciparum resistance to artemether-lumefantrine in Africa prompted the pilot introduction of multiple first-line therapies (MFT) against malaria in Kenya, potentially exposing women-of-childbearing-age (WOCBAs) to anti-malarials with unknown safety profiles in the first trimester. This qualitative study explored knowledge and perceptions among healthcare providers providing malaria treatment to WOCBAs and pregnant women., Methods: In-depth interviews were conducted with purposively selected public and private health facility (HF) and drug outlet (DO) providers within and outside the pilot-MFT area. County health managers were interviewed about their knowledge of the national treatment guidelines. Transcripts were coded by content analysis using the World Health Organization health system building blocks (leadership/governance, financing, health workforce, health information systems, access to medicines, and service delivery)., Results: Thirty providers (HF:21, DO:9) and three health managers were interviewed. Eighteen providers were from HFs in the pilot-MFT area; the remaining three and all nine DOs were outside the pilot-MFT area. The analysis revealed that providers had not been trained in malaria case management in the previous twelve months. DO providers were unfamiliar with national treatment guidelines in pregnancy and reported having no pregnancy tests. Health managers were unable to supervise DOs due to resource limitations. Providers from HFs and DOs noted poor sensitivity of malaria rapid diagnostic tests (RDTs) and hesitancy among patients who associated malaria-RDTs with HIV testing. Almost all providers reported anti-malarial stock-outs, with quinine most affected. Patient preference was a major factor in prescribing anti-malarials. Providers in HFs and DOs reported preferentially using artemether-lumefantrine in the first trimester due to the side effects and unavailability of quinine., Conclusion: Knowledge of malaria case management in drug outlets and health facilities remains poor. Improved regulation of DO providers is warranted. Optimizing treatment of malaria in pregnancy requires training, availability of malaria commodities, and pregnancy tests., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Many medicine quality problems are detected after they arrive at health facilities. Thus, critically defective medicines that may pose health risks to patients need to be withheld or recalled., Aims: To investigate the withheld and recalled medicines in relation to the types of defects, their total numbers, therapeutic categories, pharmaceutical dosage forms, and country of manufacturer during the study period., Methods: A retrospective review was performed on withheld and recalled medicines published on the publicly available National Medicines Regulatory Authority (NMRA) official website in Sri Lanka between June 2018 and August 2021. Details on substandard medicines (SM) were extracted and documented. Each record of SM was individually reviewed to determine the type of defect, subsequent action taken by NMRA, therapeutic category, pharmaceutical dosage form, and country of manufacturer., Results: A total of 163 defects were identified in 143 defective medicines, among which the most common types of defects were contamination (n = 59, 36.2%), stability defects (n = 41, 25.2%), packaging and labelling defects (n = 27, 16.6%) and active pharmaceutical ingredient defects (n = 26, 15.9%). Out of 143 total defective medicines identified, anti-infectives accounted for 41.9%, while parenteral preparations (44.0%) were found to be frequently defective. Nearly 70% of the recalled and withheld medicines were of Indian origin, and some manufacturers were identified to be repeatedly involved., Conclusions: This study revealed that contamination was the most frequent cause of defective medicines, while parenteral preparations and anti-infectives were the most susceptible pharmaceutical dosage form and therapeutic category found to be substandard, respectively. In addition, the findings show that some manufacturers were accountable for repetitive withholdings and recalls, which reflects the ignorance of quality control measures and weak regulatory inspections as a violation of Good Manufacturing Practice (GMP)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Bangladesh outperforms its Least Developed Country (LDC) status on a range of health measures including life expectancy. Its frontline medical practitioners, however, are not formally trained medical professionals, but instead lightly-trained 'village doctors' able to prescribe modern pharmaceuticals. This current study represents the most complete national survey of these practitioners and their informal 'clinics'., Methods: The study is based on a national Computer Assisted Telephone Interviewing (CATI) of 1,000 informal practitioners. Participants were sampled from all eight divisions and all 64 districts of Bangladesh, including 682 participants chosen from the purposively recruited Refresher Training program conducted by the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), supplemented with 318 additional participants recruited through snowball sampling., Primary and Secondary Outcome Measures: In addition to demographics, village doctors were asked about the characteristics of their 'clinics' including their equipment, their training, income and referral practices., Results: Three quarters of the wholly male sample had not completed an undergraduate program, and none of the sample had received any bachelor-level university training in medicine. Medical training was confined to a range of short-course offerings. Village doctor 'clinics' are highly dependent on the sale of pharmaceuticals, with few charging a consultation fee. Income was not related to degree of short-course uptake but was related positively to degree of formal education. Finally, practitioners showed a strong tendency to refer patients to the professional medical care system., Conclusions: Bangladesh's village doctor sector provides an important pathway to professional, trained medical care, and provides some level of care to those who cannot afford or otherwise access the nation's established healthcare system. However, the degree to which relatively untrained paramedical practitioners are prescribing conventional medicines has concerning health implications., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: Low adherence is a major challenge in healthcare worldwide, being particularly dangerous for patients with chronic diseases, such as cardiovascular diseases and heart failure, where strict adherence is essential. Non-adherence is observed in almost half of patients, and the consequences encompass a lack of therapeutic effects, health deterioration, decreased quality of life, and even death. For cardiovascular patients, the great importance of health education and pharmaceutical education can be provided within pharmaceutical care in community pharmacies. Therefore, our study aimed at evaluating the level of satisfaction with the "Healthy Heart" pharmaceutical service, in which patients received pictograms with dosage information affixed to their medication., Material and Methods: The study was designed for patients who had been prescribed an antiplatelet medication for the first time. The patients were recruited by 577 pharmacies that took part in the study after completing a special course. Ultimately, 1590 patients were enrolled in the study. The project ran from November 2019 to January 2022., Results: Most of patients had a positive attitude to the "Healthy Heart" pharmaceutical service. More than 85% of the respondents were of the opinion that the pictograms facilitated the use of the medication, and 81.7% of the respondents stated that the system of labels helped in adherence. Over 66% of the respondents thought that such labels should be included in pharmacy services, and 77.92% of the participants reported that this system of labelling medications should be offered through all pharmacies., Conclusions: Pharmaceutical labels in the pharmacists' everyday practice can largely improve patient adherence. These efforts, provided as part of their pharmaceutical services, can have a huge influence on optimisation of patient health outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) are highly effective in treating rheumatoid arthritis (RA), albeit high drug cost has restricted their use in many countries. As a countermeasure, Norway implemented pharmaceutical tendering as a cost-reducing strategy. The aim of this study was to assess the annual proportion of different b/tsDMARDs registered to treat RA patients under the influence of a Norwegian pharmaceutical tendering between 2010 and 2019., Method: The data is collected from ten Norwegian outpatient centers. The included patients are categorized as naïve, non-naïve, and current b/tsDMARD users. 13 individual b/tsDMARDs are assessed and compared with the tender rankings from each year. Overview of subcutaneous (sc) with per oral vs. intravenous (iv) and biosimilars vs. non-biosimilar are also described., Result: The tender-winning b/tsDMARD was the most or second most used drug in nine out of ten years for naïve users, seven for non-naïve users, and twice for current users. The average sum of the highest and second highest proportion among naïve, non-naïve, and current b/tsDMARD users were 75%, 53%, and 50% during the ten years, respectively. The tender-winning drug was iv in eight out of ten years. However, the average total proportion of sc and per oral b/tsDMARDs was about 70% for naïve b/tsDMARD users, 50% for non-naïve b/tsDMARD users, and 60% for current b/tsDMARD users. The main contributors to sc and per oral b/tsDMARD were etanercept (reference and biosimilar) and certolizumab pegol. The main contributors to iv b/tsDMARD were rituximab reference and infliximab biosimilar. Despite low-ranking offers, rituximab reference (offered as a second-line drug) often achieved a high proportion among non-naïve and current b/tsDMARD users. After the introduction of biosimilars, their average proportion was about 40%, 40%, and 20% for naïve, non-naïve, and current b/tsDMARD users, respectively., Conclusion: Based on observed data, a higher tender rank was associated with a higher proportion among naïve and non-naïve b/tsDMARD users. However, in most cases, sc b/tsDMARDs achieved a higher proportion with lower tender ranks than iv b/tsDMARDs with higher tender ranks., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Several jurisdictions in Canada have recently considered decriminalizing possession of illicit drugs for personal use (henceforth, simple possession) as part of their responses to the ongoing drug toxicity/overdose crisis. In this context, we sought to examine an early implementation case of a de facto depenalization policy of simple possession offences in Vancouver, Canada, that was enacted in 2006. Specifically, we characterized experiences of people who use drugs (PWUD) whose drugs were discretionally seized by police without arrest., Methods: Data were derived from three prospective cohorts of community-recruited PWUD in Vancouver over 16 months in 2019-2021. We conducted multivariable generalized estimating equations analyses to determine the prevalence of and factors associated with drug seizure. Sub-analyses used data collected in 2009-2012 and examined the trends over time., Results: Among 995 participants who were interviewed in 2019-2021, 63 (6.3%) had their drugs seized by police at least once in the past 6 months. In multivariable analyses, factors significantly associated with drug seizure included: homelessness (adjusted odds ratio [AOR]: 1.98; 95% confidence interval [CI] 1.09-3.61), working in the unregulated drug market (AOR: 4.93; 95% CI 2.87-8.49), and naloxone administration (AOR: 2.15; 95% CI 1.23-3.76). In 2009-2012, 67.8% reported having obtained new drugs immediately after having their drugs seized by police. Odds of drug seizure were not significantly different between the two time periods (2019-2021 vs. 2009-2012) (AOR: 0.93; 95% CI: 0.64-1.35)., Conclusions: Despite the depenalization policy, the Vancouver Police Department has continued to seize illicit drugs from PWUD, even in cases where no arrest occurred. This policing practice may create health and safety risks for PWUD as it forces PWUD to increase the engagement with the unregulated illicit drug market. Our findings support calls for abolishing this often-undocumented discretionary policing practice that may exacerbate ongoing health inequities and interfere with peer-based overdose prevention efforts., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Over 40% of the six million dry metric tons of sewage sludge, often referred to as biosolids, produced annually in the United States is land applied. Biosolids serve as a sink for emerging pollutants which can be toxic and persist in the environment, yet their fate after land application and their impacts on human health have not been well studied. These gaps in our understanding are exacerbated by the absence of systematic monitoring programs and defined standards for human health protection., Methods: The purpose of this paper is to call critical attention to the knowledge gaps that currently exist regarding emerging pollutants in biosolids and to underscore the need for evidence-based testing standards and regulatory frameworks for human health protection when biosolids are land applied. A scoping review methodology was used to identify research conducted within the last decade, current regulatory standards, and government publications regarding emerging pollutants in land applied biosolids., Results: Current research indicates that persistent organic compounds, or emerging pollutants, found in pharmaceuticals and personal care products, microplastics, and per- and polyfluoroalkyl substances (PFAS) have the potential to contaminate ground and surface water, and the uptake of these substances from soil amended by the land application of biosolids can result in contamination of food sources. Advanced technologies to remove these contaminants from wastewater treatment plant influent, effluent, and biosolids destined for land application along with tools to detect and quantify emerging pollutants are critical for human health protection., Conclusions: To address these current risks, there needs to be a significant investment in ongoing research and infrastructure support for advancements in wastewater treatment; expanded manufacture and use of sustainable products; increased public communication of the risks associated with overuse of pharmaceuticals and plastics; and development and implementation of regulations that are protective of health and the environment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Oral administration is preferred over other drug delivery methods due to its safety, high patient compliance, ease of ingestion without discomfort, and tolerance of a wide range of medications. However, oral drug delivery is limited by the poor oral bioavailability of many drugs, caused by extreme conditions and absorption challenges in the gastrointestinal tract. This review thoroughly discusses the targeted drug vehicles to the intestinal lymphatic system (ILS). It explores the structure and physiological barriers of the ILS, highlighting its significance in dietary lipid and medication absorption and transport. The review presents various approaches to targeting the ILS using spatially precise vehicles, aiming to enhance bioavailability, achieve targeted delivery, and reduce first-pass metabolism with serve in clinic. Furthermore, the review outlines several methods for leveraging these vehicles to open the ILS window, paving the way for potential clinical applications in cancer treatment and oral vaccine delivery. By focusing on targeted drug vehicles to the ILS, this article emphasizes the critical role of these strategies in improving therapeutic efficacy and patient outcomes. Overall, this article emphasizes the critical role of targeted drug vehicles to the ILS and the potential impact of these strategies on improving therapeutic efficacy and patient outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)