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What Is Known? and Objective. Immune checkpoint inhibitors (ICIs) play an important role in various cancers. The efficacy and safety of rechallenge with ICIs after immune-related adverse events (irAEs) were not well known. Accumulating studies report inconsistent findings. Thus, we conducted an updated meta-analysis by including more studies. Methods. We searched PubMed, Web of Science, Embase, and Cochrane Library for studies reporting the rechallenge of ICIs after irAEs. The evaluation outcomes included the incidence of irAEs, objective response rate (ORR), and disease control rate (DCR). Results and Discussion. A total of 896 ICI rechallenge cases from 24 studies were included. Compared to the initial treatment with ICIs, rechallenge showed a higher incidence of all-grade irAEs (OR, 2.78; 95% CI, 1.51–5.10; p = 0.001) and high-grade irAEs (OR, 1.88; 95% CI, 1.27–2.78; p = 0.002), but ORR (OR, 1.01; 95% CI, 0.55–1.84; p = 0.97) and DCR (OR, 1.21; 95% CI, 0.68–2.15; p = 0.52) were not further improved after the rechallenge of ICIs. What Is New? and Conclusion. More studies are included in this paper to compare and analyze the efficacy and safety of ICIs after rechallenge, so as to update the previous meta-analyses, and finally get different conclusions from the previous meta-analyses in terms of safety. Our results suggest that rechallenged ICIs after irAEs showed similar efficacy and lower safety than initial ICIs. However, these results need to be further verified by high-quality studies with large samples. In addition, we added subgroup analysis not available in previous meta-analyses to explore the association of cancer type, age, and gender factors with the incidence of irAE after ICI rechallenge. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) have transformed the therapeutic approach to diverse malignancies, leading to substantial enhancements in patient prognosis. However, along with their benefits, ICIs also increase the incidence of immune-related adverse events (irAEs). In the present paper, we highlight four cases of carpal tunnel syndrome (CTS) as an uncommon manifestation of toxicity induced by ICIs. Although diagnosed with different malignancies, the patients were undergoing ICI therapy when they developed CTS-consistent side effects accompanied by severe neuropathy. Prompt treatment with corticosteroids, intravenous immunoglobulins, or methotrexate resulted in complete symptomatic relief for all patients. This article therefore emphasizes the importance of recognizing and managing rare adverse events associated with ICI use to ensure optimal patient care. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibition therapy (ICIT) is an emerging field in oncology especially opening new horizons to chemotherapy refractory patients. However, immune-related adverse events (irAEs) and undesired response patterns such as progression after the initial good response in a subset of patients pose a major challenge and drawback to ICIT. This paper provides deep insight into ICIT related bottlenecks and corresponding effective management and combat strategies for very complex complications. Methods: The relevant literatures from PubMed have been reviewed. Based on obtained information, rigorous and exhaustive analyses have been made to present novel methods and strategies against ICIT drawbacks and bottlenecks. Results: The results show that baseline biomarker tests are very crucial to identify suitable candidates for ICIT and frequent assessments throughout ICIT help to recognize possible irAEs at early stages. Equally important are the necessity for mathematical definitions for the ICIT success rate and optimum duration, and the development of combat mechanisms against loss of sensitivity within the tumor microenvironment (TME). Conclusion: Rigorous management approaches are presented for mostly observed irAEs. Furthermore, for the first time in the literature, a non-linear mathematical model is invented to measure the ICIT success rate and to decide about the optimum ICIT duration. Finally, a strategy against tumor plasticity is introduced. [ABSTRACT FROM AUTHOR]

Background: Managing multidrug-resistant (MDR) HIV infections in children is particularly challenging due to the lack of experience with new drugs in the pediatric setting. Second-line albuvirtide (ABT) with an optimized antiretroviral background therapy was approved for adults and adolescents after first-line treatment failure. This paper describes the treatment outcomes and adverse effects of an ABT-based dual-active antiretroviral treatment regimen in a child with MDR HIV strains. Case presentation: A 13 year-old Chinese female patient infected with MDR HIV strains showed a decrease in viral load (from 4.48 log10 to 1.73 log10) and an increase in CD4 + T cells (from 15 to 308 cells/µl) after 12 months of treatment with an ABT-based antiretroviral regimen. The child showed no relevant drug-related adverse reactions. Conclusions: The case reported here could suggest that an ABT-based antiretroviral therapy might be beneficial and without relevant toxicity in children with MDR HIV. Infectiologists specializing in managing HIV should be prepared to manage an increasing number of children with MDR HIV. ABT might be a new treatment option for MDR HIV infection in children. [ABSTRACT FROM AUTHOR]

Damkier and Andersen do not seem to be convinced that patients carrying a genetic variant that has shown to significantly influence a drug's metabolism need optimization of their drug treatment by adjusting the dose. The fact that we used self-reported ADRs, inventoried by a research nurse, can also be seen as a strength of the study in an era of recognition of the value of patient-reported outcome measurement. When the analysis was performed in all patients after correction for the casemix, the effect size decreased from 0-30 to 0-13 (no longer significant), whereas the effect size in patients with an actionable genotype increased from 0-30 to 0-39 (appendix pp 30-33 in The Lancet paper). [Extracted from the article]

This document is a response to a comment made by Dr. Yoshiro Noguchi regarding a paper titled "Drugs That Interact With Colchicine Via Inhibition of Cytochrome P450 3A4 and P-Glycoprotein: A Signal Detection Analysis Using a Database of Spontaneously Reported Adverse Events (FAERS)." The authors of the response address two main issues raised by Dr. Noguchi: the potential for false signals due to overwhelming reports in concomitant medications, and the statistical approach used. The authors clarify that their study aimed to understand the potential impact of known interactions rather than finding unknown interactions. They also explain their methodology, which involved analyzing situations with at least 5 reports mentioning the adverse event and both medications. The authors disagree with the claim that their methods are questionable and defend their approach as conservative and transparent. [Extracted from the article]

The long-term and potential rare side effects of new immunomodulating drugs for the treatment of multiple sclerosis (MS) are often not well known. Spontaneous case report systems of adverse drug effects are a valuable source in pharmacovigilance, but have several limitations. Primary data collections within registries allow a comprehensive analysis of potential side effects, but face several challenges. This article will outline the chances and challenges of registry-based adverse event reporting, using the example of the German immunotherapeutic registry REGIMS. REGIMS is an observational, clinical multicenter registry that aims to assess the incidence, type, and consequences of side effects of MS immunotherapies. Patients treated with an approved MS medication are recruited by their physicians during routine visits in hospitals, outpatient clinics, and MS-specialized practices. REGIMS incorporates an electronic physician-based documentation in each center and a paper-based patient documentation, both at baseline and regular follow-up visits. By the end of 2019, 43 REGIMS centers were actively recruiting patients and performing follow-up documentations. The majority of the first 1000 REGIMS patients were female (69.3%), had relapse-remitting MS (89.8%), and were treated with a second-line therapy. During the implementation of REGIMS, several logistic and procedural challenges had to be overcome, which are outlined in this paper. Pharmacovigilance registries such as REGIMS provide high-quality primary data from a specific patient population in a real-world care setting and enable pharmacovigilance research that cannot be carried out using secondary data. Despite the logistic and procedural challenges in establishing a multicenter pharmacovigilance registry in Germany, the advantages outweigh the drawbacks. [ABSTRACT FROM AUTHOR]

Background: Mild non‐immediate reactions (NIR) to beta‐lactams (βLs) are the most common manifestation of adverse drug reactions in children, and the drug provocation test (DPT) remains the gold standard for diagnosis. However, there are still controversies about the protocol that should be used, especially regarding the administration of doses and the DPT length. Objective: This study aimed to evaluate a pediatric population with a history of mild NIR to amoxicillin (AMX) or to amoxicillin‐clavulanic acid (AMX/CL) who underwent a diagnostic workup including a DPT with the culprit drug, to understand if a graded DPT or, instead, a single full dose could be the most appropriate way of administration in clinical practice. Methods: The data of children were retrospectively analyzed for a 5‐year period, with demographic and clinical characteristics collected. We reported the allergy workup and the results of the DPT performed with the administration of incremental doses and a prolonged DPT at home for a total of 5 days. Results: Three hundred fifty‐four patients were included. Overall, 23/354 (6.5%) DPTs were positive: 11/23 patients showed a reaction after 2–8 h after the last dose on the 1st or 2nd day (1 reacted 30 min after the last dose), 1/23 reacted with urticaria 30 min after the first dose, 11/23 reacted at home on the 5th day of the DPT. Conclusion: This paper indirectly suggests that a single therapeutic dose administered on the 1st day of a DPT could be safe in the diagnostic workup of mild NIR to AMX/CL. Moreover, this could be less time‐consuming as patients would spend less time in the hospital, also considering the public health restrictions imposed during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: There is a need to strengthen the evidence base regarding medication use during pregnancy and to facilitate the early detection of safety signals. EudraVigilance (EV) serves as the primary system for managing and analysing information concerning suspected adverse drug reactions (ADRs) within the European Economic Area. Despite its various functionalities, the current format for electronic submissions of safety reports lacks a specific data element indicating medicine exposure during pregnancy. Objective: This paper aims to address the limitations of existing approaches by developing a rule-based algorithm in EV that more reliably identifies cases that are truly representative of an ADR during pregnancy. Methods: The study utilised the standardised MedDRA query (SMQ) 'Pregnancy and neonatal topics' (PNT) as a benchmark for comparison. Recognising that the SMQ PNT also retrieves healthy pregnancy outcomes, contraceptive failure, failed abortifacients as well as ADRs not associated with pregnancy, a novel algorithm was tailored to improve the accuracy of identifying suspected ADRs occurring during pregnancy. Results: Upon testing, the algorithm demonstrated superior performance, correctly predicting 90% of cases reporting an ADR during pregnancy, compared to 54% achieved by the SMQ PNT. The implementation of the algorithm in EV led to the retrieval of 202,426 cases. Conclusion: The development and successful testing of the novel algorithm represents a step forward in pregnancy-specific signal detection in EV. Because signals associated with pregnancy may be diluted in a large database such as EV, this study lays the groundwork for future research to evaluate the effectiveness of disproportionality methods on a more refined subset of pregnancy-related ADR reports. [ABSTRACT FROM AUTHOR]

This paper critically examines the approach to studying and intervening in organizations that derives from the work of Melanie Klein. It proposes that Klein's emphasis on reparation, while clearly valuable for effecting change, can also induce undue guilt that stymies employee subjectivity and damages the organization. The term "reparation compulsion" is offered to capture this particular dynamic. Defined as the incessant drive to atone for guilt, reparation compulsion has both individual and collective correlates that together constitute a unique and hitherto unexplored organizational pathology. Two vignettes are used to demonstrate the limits of reparation in a work setting before turning to Menzies' classic case study of a nursing service, which is revisited in light of the pitfalls of guilt-driven labor. Together, these illustrations revise and expand upon Menzies' concept of social defense, placing reparation compulsion at the core of a newfound "depressive" social defense system that has direct repercussions for those working in the caring professions, and particularly those afflicted with "compassion fatigue." Specifically, the argument is made that compassion fatigue is not just an unfortunate side effect of caring, but constitutive of an organization in which repairing others requires a chronic disrepair of the self. The paper concludes with discussing the implications for the psychoanalytic study of organizations. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to challenge the constructs regularly used by organisations around the world for the development of leadership. Design/methodology/approach: This is an opinion piece based on direct observation of hundreds of organisations over the years. Findings: The regular approaches used for the development of leadership skills in organisations have consistently failed to deliver against its promise. Moreover, it is often the case that organisations pursue new "solutions" to bridge the leadership gap, often to discover that their new approach not only failed to develop the skills needed but also had the side effect of distracting vast amounts of attention. This paper describes what, if not the various taxonomies that describe, "good leadership" looks like really and how it delivers sustainable and effective leadership transformation. Originality/value: This piece challenges the status quo, offering a more powerful way of connecting people with the purpose of their work, increasing the impact that individual leadership could have in the creation of value for all stakeholders, including themselves. [ABSTRACT FROM AUTHOR]

aimed at identifying the best practice for counseling around depression in community and outpatient pharmacies, resulting in a draft guideline, proposing key steps and an algorithm for integration of community pharmacists into care for patients with depression. Methods: A literature review was performed followed by a detailed analysis, for the purpose of creation a short draft document used as a basis for creation of a guideline for pharmaceutical care for patients with depression. The technological scheme PRISMA flow diagram was applied. The paper is based on current knowledge, taking into consideration already published articles, guidelines, and recommendations about pharmaceutical care for patients with depression, giving a basis for further studies. Results: This paper includes two main sections: 1) depression – a short description of the main symptoms, risk factors and pharmacotherapy guidelines available in Bulgaria important for the purposes of ensuring qualitative community-based pharmaceutical care; and  2) the pharmacists' role in providing high-quality care – the main aspects of pharmaceutical care for patients with depression with specific examples. Conclusion: The involvement of pharmacists in supporting depressive patients is crucial taking into account the specific characteristics of the pharmacological treatment: delayed onset of clinical results, risks in case of sudden pharmacotherapy abruption without physician consultation, multiple adverse drug reactions and drug–drug, drug–food and drug–alcohol interactions, etc. The current article could also be used as an initial document for creating a methodological guideline for providing pharmaceutical care services for patients with depression. [ABSTRACT FROM AUTHOR]

Background: A number of methods exist for the risk assessment of hospital inpatients to determine the likelihood of patients experiencing drug-related problems (DRPs), including manual review of a patient's medication (medication reviews) and more complex electronic assessment using decision support alerts in electronic prescribing systems. A systematic review was conducted to determine the evidence base for potential risks associated with adult hospital inpatients that could not only lead to medication-related issues but might also be directly associated with pharmacist intervention. Objectives: The aims were to perform a systematic review of the literature in order to (1) identify all measurable risk factors associated with adult hospital inpatients that potentially lead to a pharmaceutical intervention; (2) critically evaluate the quality of the identified research; and (3) further subcategorise potential risk factors, so that pharmaceutical services may be targeted to patients 'at risk' by identifying potential risk factors in a patient's electronic hospital record. Methods: A systematic review, conducted in June 2013, searched ten medical literature databases for all papers identifying risks leading to pharmacist interventions or DRPs, adverse drug events (ADEs), adverse drug reactions, drug errors (where not included in the definition of an ADE), and medication-related problems. The search identified 7720 titles, from which 120 papers were sourced. A hand search of a further 11 journals was also performed. No date restrictions were imposed. All primary research and literature reviews were included. Summary articles were excluded with the exception of literature reviews. The inclusion of search outputs was validated by a third party pharmacy research graduate. Results: From the 7720 titles, 38 publications met the inclusion criteria for the review. The ten most frequently reported risk factors associated with medication-related issues that may potentially lead to a hospital pharmaceutical intervention are as follows (ranked in descending order of frequency): prescription of certain drugs or classes of drugs, polypharmacy, elderly patients (defined as over 65 years), female gender, poor renal function, the presence of multiple comorbidities, length of patient stay, history of drug allergy or sensitivity, patient compliance issues, and poor liver function. The ten classes of drugs most frequently reported to be associated with medication-related issues leading to a hospital pharmaceutical intervention are as follows (ranked in descending order of frequency): intravenous antimicrobials, thrombolytics/anticoagulants, cardiovascular agents, central nervous system agents, corticosteroids, diuretics, chemotherapy, insulin/hypoglycaemics, opiates, and anti-epileptics. Conclusion: Review of the literature identified 38 papers, from which the ten most frequently reported risk factors linked with factors that are potentially associated with hospital pharmaceutical interventions (all definitions included) were identified. No papers were identified that demonstrated a direct causal relationship between a potential risk factor and hospital pharmaceutical interventions. All of the potential risk factors associated with problems with the use of medicines can be identified from patient records on admission to hospital. These risk factors may be used to identify patients at risk, with a view to targeting pharmaceutical intervention in order to minimise risks of problems with medicines and improve efficiency of clinical pharmacy services. [ABSTRACT FROM AUTHOR]

Through the influence of neoliberal ideas, many critical infrastructures that used to be under public ownership have been opened up for market competition. Using the Swedish railway system as a case, this paper empirically explores whether such reforms have given rise to common‐pool resource problems, and discusses possible implications. The results show that institutional restructuring has created challenges related to balancing the use of the infrastructure with a sufficient level of maintenance. The paper concludes that the main value of analysing critical infrastructures from the perspective of common‐pool resources is the possibility of juxtaposing the way organizational and institutional interactions across scales generate both short‐term gains and long‐term negative side effects influencing reliability and safety. [ABSTRACT FROM AUTHOR]

An important mission statement for modern dentistry is to maintain patients' implants and teeth for a lifetime. As a corollary, a standardized dental caries risk classification should provide the basis for evidence-based specific therapies. This paper proposes that interproximal caries lesions, also termed "restorative invasion," which destroys natural anatomical tooth structure with periodontal and occlusal sequelae, is a key factor in the cascade of destruction of the dentition and periodontitis. Thus it can serve as the basis for caries risk assessment. The standardized Dental Risk Classification system proposed here can provide a basis for therapeutic modalities as well as for public health assessment and insurance reimbursement. [ABSTRACT FROM AUTHOR]

A drug's pharmacokinetic (PK) profile will determine its dose and the frequency of administration as well as the likelihood of observing any adverse drug reactions. It is important to understand these PK properties as early as possible in the drug discovery process, ideally, to accurately predict these prior to synthesising the molecule leading to significant improvements in efficiency. In this paper, we describe the approaches used within AstraZeneca to improve our ability of predicting the preclinical and human pharmacokinetic profiles of novel molecules using machine learning and artificial intelligence. We will show how combining chemical structure-based approaches with experimentally derived properties enables improved predictions of in vivo pharmacokinetics and can be extended to molecules that go beyond the classical Lipinski's rule-of-five space. We will also discuss how combining these in vitro and in vivo predictive models could ultimately improve our ability to predict the human outcome at the point of chemical design. [ABSTRACT FROM AUTHOR]

In June 2021, FDA released a Draft Guidance on Sponsor Responsibilities for IND Safety Reporting and cited components of a recommended Safety Surveillance Plan (SSP). To meet the expectations of the 2021 FDA guidance, sponsors should document their plan for aggregate safety assessment. The Drug Information Association-American Statistical Association Interdisciplinary Safety Evaluation scientific working group has proposed an Aggregate Safety Assessment Plan (ASAP) that addresses this recommendation. The 2021 FDA guidance also discusses potential strategies for unblinded review of safety data from ongoing studies by an independent Assessment Entity, which could occur via planned periodic evaluations or "triggered" reviews based on blinded data assessments. The Assessment Entity reviewing unblinded data makes recommendations as to whether the threshold has been met for submission of an aggregate IND safety report. In this paper, we discuss how the ASAP supports IND aggregate safety reporting decisions, including elements to be included in a proposed SSP appendix to the ASAP. In addition, the authors advocate for the benefits of developing a charter (or specific section of the Data Monitoring Committee charter, if applicable) that describes the responsibilities and conduct of the Assessment Entity. With these components in place, study sponsors will meet the objective of having clearly defined processes for the monitoring of clinical trial safety data in aggregate and making IND safety reporting decisions. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense pruritus. AD is harmful to both children and adults, but its pathogenic mechanism has yet to be fully elucidated. The development of mouse models for AD has greatly contributed to its study and treatment. Among these models, the exogenous drug-induced mouse model has shown promising results and significant advantages. Until now, a large amount of AD-related research has utilized exogenous drug-induced mouse models, leading to notable advancements in research. This indicates the crucial significance of applying such models in AD research. These models exhibit diverse characteristics and are highly complex. They involve the use of various strains of mice, diverse types of inducers, and different modeling effects. However, there is currently a lack of comprehensive comparative studies on exogenous drug-induced AD mouse models, which hinders researchers' ability to choose among these models. This paper provides a comprehensive review of the features and mechanisms associated with various exogenous drug-induced mouse models, including the important role of each cytokine in AD development. It aims to assist researchers in quickly understanding models and selecting the most suitable one for further investigation. [Display omitted] • Exogenous-drugs induced mouse models are very helpful in studying the pathogenesis of AD in humans. • Hapten-induced mouse models are cost-effective but time-consuming. • OVA-induced mouse models are widely applicable. • MC903-induced mouse models are ideal for rapid AD modelling. [ABSTRACT FROM AUTHOR]

This paper describes the patient-patient interactions (PPIs) graph extraction framework from patient’s review transcripts. The concept is to visualise patients as nodes and interactions representing links. Links are made based on review text similarity. Nodes are categorized as positive or negative according to the patient’s attitude toward a given drug. Attitudes are then utilized to categorize the links as supporting or opposing the use of a certain drug. If both patients share the same attitude: negative (severe side effect) or positive (moderate side effect), the relationship is considered supportive; if not, the link is considered opposed. Resulting graph represent a drug as a dispute between two factions arguing on related drug. The framework is explained and evaluated using a dataset included 3,763 patients’ reviews linked to 255 different drugs, -predictive-value (0.37). We argue that, this is caused by derogatory jargon that is an expected feature of patient’s review. The true-negative-recognition-rate is 0.70 and true-positive-recognition-rate is 0.54. Total-average-accuracy, which is independent of class priors, is 0.66. Results show that, it is possible to use text proximity measures and sentiment analysis to capture PPIs structure. [ABSTRACT FROM AUTHOR]

Introduction: Spontaneous reporting of adverse events (AEs) is a mainstay of pharmacovigilance, and an ongoing challenge is how to ensure that more high-quality reports are collected for comprehensive information provision. The Med Safety App, a smartphone-based application, was launched in Nigeria in November 2020 to provide an electronic platform for users to seamlessly report AEs. There has been a paucity of evidence on the use of this application or other mobile applications for reporting adverse drug reactions/AEs following immunization in the Nigerian environment. Objective: The aim of this study was to evaluate the trends in adverse event reporting before and after the introduction of the Med Safety App in Nigeria. Methods: This was a retrospective, observational study using data from the VigiFlow database to compare adverse event reporting in Nigeria before and after the deployment of the Med Safety App. The baseline period was 1st April 2019 to 30th October 2020 and the comparison period was 1st November 2020 to 31st May 2022. We used Vigilance Hub, the back-end system for the Med Safety App, to extract data on App downloads and de-identified user statistics. Data were summarized using descriptive statistics, frequencies and proportions. Quality was assessed by assigning a completeness score to each individual case safety report. The Kruskal–Wallis test was used to test for differences in medians between groups. Results: Following deployment of the App, the Nigerian National Pharmacovigilance Centre recorded an increase in the total number of adverse event reports received in VigiFlow, from 2051 in the baseline period to 18,995 following deployment of the App, with 81.7% of those reported via the Med Safety App. There was a reduction in the proportion of paper-based reporting from 98.4 to 15.7% post-deployment, and direct reporting by consumers increased from 2.7 to 17.6%. Of the 15,526 reports submitted via the App, 15,111 (97.3%) had a completeness score above 70% and 6993 (45%) had a completeness score of 100%. The median completeness score of adverse event reports on the Med Safety App was 6 out of 7. On bivariate analysis using the Kruskal–Wallis test, there was an association between means of reporting and completeness score, and this association was significant, with a p value of 0.0001, which may reflect the validation rules that are applied within the App. Conclusion: Deployment of the Med Safety App increased both the number and quality of adverse event reports; however, more awareness and capacity building are needed to strengthen and sustain reporting on the tool by all categories of healthcare professionals and consumers/patients. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICI) may trigger autoimmune neurological conditions, including movement disorders (MD). Objectives: The aim of this study was to characterize MDs occurring as immune‐related adverse events (irAEs) of ICIs. Methods: A systematic literature review of case reports/series of MDs as irAEs of ICIs was performed. Results: Of 5682 eligible papers, 26 articles with 28 patients were included. MDs occur as a rare complication of cancer immunotherapy with heterogeneous clinical presentations and in most cases in association with other irAEs. Inflammatory basal ganglia T2/fluid attenuated inversion recovery abnormalities are rarely observed, but brain imaging is frequently unrevealing. Cerebrospinal fluid findings are frequently suggestive of inflammation. Half of cases are associated with a wide range of autoantibodies. Steroids and ICI withdrawal usually lead to improvement, even though some patients experienced relapses or a severe clinical course. Conclusion: MDs are a rare complication of ICIs that should be promptly recognized to offer patients a correct diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Clinical pharmacists add significant value to the health care team and are associated with reduced hospital mortality, drug costs, length of stay, and adverse drug reactions. However, there remains a paucity of evaluative data regarding optimal clinical pharmacy practice models. Identifying optimal patient (or bed)‐to–clinical pharmacist ratios is one mechanism to assess the allocation of resources. The ACCP Task Force on Clinical Pharmacy Services was charged with developing a white paper to examine optimal ratios in different care settings, considering confounders and other factors that affect the interpretation of ratio data. The committee performed an extensive search of the pharmacy, medical, and nursing literature to identify existing data on provider‐to‐patient ratios. Recommendations on ratios are mainly from survey data or statements from various health care organizations. Many factors affect the capacity of clinical pharmacists to achieve patient care and non‐patient care responsibilities. Examples include general differences in baseline expectations; nonstandardized program performance metrics; variable hospital/practice setting types; variable patient acuity and complexity; competing priorities and other resources; industry‐wide rates of and variability in addressing burnout; inconsistent means for justifying numbers and historical corporate structures; and external endorsements and mandates. Although some areas of practice such as critical care pharmacy have more robust evidence for specific ratios, others such as pediatrics are far less clear. A clinical pharmacist ratio must be established as a starting point. This will allow for better allocation today and serve as a springboard for future determinations. Furthermore, clinical pharmacist ratios should be preserved to offer reliable patient care 365 days per year. As clinical pharmacist services shift from beneficial to essential, continuous daily patient care services must be the practice model moving forward. [ABSTRACT FROM AUTHOR]

Although psychoactive drugs have their therapeutic values, they have been implicated in the pathogenesis of male infertility. This study highlights psychoactive drugs reported to impair male fertility, their impacts, and associated mechanisms. Published data from scholarly peer-reviewed journals were used for the present study. Papers were assessed through AJOL, DOAJ, Google Scholar, PubMed/PubMed Central, and Scopus using Medical Subjects Heading (MeSH) indexes and relevant keywords. Psychoactive drugs negatively affect male reproductive functions, including sexual urge, androgen synthesis, spermatogenesis, and sperm quality. These drugs directly induce testicular toxicity by promoting ROS-dependent testicular and sperm oxidative damage, inflammation, and apoptosis, and they also suppress the hypothalamic-pituitary–testicular axis. This results in the suppression of circulating androgen, impaired spermatogenesis, and reduced sperm quality. In conclusion, psychoactive drug abuse not only harms male sexual and erectile function as well as testicular functions, viz., testosterone concentration, spermatogenesis, and sperm quality, but it also alters testicular histoarchitecture through a cascade of events via multiple pathways. Therefore, offering adequate and effective measures against psychoactive drug-induced male infertility remains pertinent. [ABSTRACT FROM AUTHOR]

Based on the Theory of Planned Behavior, this paper explores the perceptions of the COVID-19 vaccine among South Asian communities residing in the UK. Thirty-eight semi-structured interviews were conducted using a qualitative approach and analyzed using thematic analysis. Participants represented Indian, Pakistani, Bangladeshi, Sri Lankan, Afghani, and Nepali backgrounds. The participants revealed that family and community influence their perceptions of the COVID-19 vaccine. The results suggest that normalizing vaccine acceptance, addressing unknown side effects, and popularizing vaccine efficacy data will increase vaccine uptake within the South Asian community in the UK. [ABSTRACT FROM AUTHOR]

The kidney is critical in the human body's excretion of drugs and their metabolites. Renal transporters participate in actively secreting substances from the proximal tubular cells and reabsorbing them in the distal renal tubules. They can affect the clearance rates (CLr) of drugs and their metabolites, eventually influence the clinical efficiency and side effects of drugs, and may produce drug–drug interactions (DDIs) of clinical significance. Renal transporters and renal transporter-mediated DDIs have also been studied by many researchers. In this article, the main types of in vitro research models used for the study of renal transporter-mediated DDIs are membrane-based assays, cell-based assays, and the renal slice uptake model. In vivo research models include animal experiments, gene knockout animal models, positron emission tomography (PET) technology, and studies on human beings. In addition, in vitro–in vivo extrapolation (IVIVE), ex vivo kidney perfusion (EVKP) models, and, more recently, biomarker methods and in silico models are included. This article reviews the traditional research methods of renal transporter-mediated DDIs, updates the recent progress in the development of the methods, and then classifies and summarizes the advantages and disadvantages of each method. Through the sorting work conducted in this paper, it will be convenient for researchers at different learning stages to choose the best method for their own research based on their own subject's situation when they are going to study DDIs mediated by renal transporters. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to explore and theorise about the desistance process of Maltese mothers who previously used drugs. The study unpacks how initial and continued desistance from high-risk drug use (HRDU) is impacted by being a mother within the Maltese context and identifies contingencies for desistance and examines how they are negotiated along the desistance pathways. Design/methodology/approach: The study adopted a symbolic interactionist-inspired career framework and involved in-depth exploration of trajectories of mothering and desistance of eight Maltese women with a history of HRDU. Data were gathered through in-depth interviews and analysis used an evolved grounded theory methodology. Findings: Four explanatory categories were identified in the interview data to document the role of mothering in the various pathways to desistance recounted by the women. These are: becoming a mother; differing pathways of desistance in relation to mothering; the lived experience; identity negotiation and transformation. This study highlights how identity fluidity and transformation is central to the desistance process. Practical implications: The paper aims to inform policy and practice with mothers who use drugs and their families and has important implications for the development and delivery of gender transformative interventions. Originality/value: This study challenges taken-for-granted beliefs about the influence of mothering on desistance and identifies the complexities involved. [ABSTRACT FROM AUTHOR]

Introduction: Underreporting is a major limitation of the voluntary reporting system of adverse drug reactions (ADRs). A 2009 systematic review showed the knowledge and attitudes of health professionals were strongly related with underreporting of ADRs. Objective: Our aim was to update our previous systematic review to determine factors (sociodemographic, knowledge and attitudes) associated with the underreporting of ADRs by healthcare professionals. Methods: We searched the MEDLINE and EMBASE databases for studies published between 2007 and 2021 that met the following inclusion criteria: (1) published in English, French, Portuguese or Spanish; (2) involving health professionals; and (3) the goal was to evaluate factors associated with underreporting of ADRs through spontaneous reporting. Results: Overall, 65 papers were included. While health professional sociodemographic characteristics did not influence underreporting, knowledge and attitudes continue to show a significant effect: (1) ignorance (only serious ADRs need to be reported) in 86.2%; (2) lethargy (procrastination, lack of interest, and other excuses) in 84.6%; (3) complacency (the belief that only well tolerated drugs are allowed on the market) in 46.2%; (4) diffidence (fear of appearing ridiculous for reporting merely suspected ADRs) in 44.6%; and (5) insecurity (it is nearly impossible to determine whether or not a drug is responsible for a specific adverse reaction) in 33.8%, and the absence of feedback in 9.2%. In this review, the non-obligation to reporting and confidentiality emerge as new reasons for underreporting. Conclusions: Attitudes regarding the reporting of adverse reactions continue to be the main determinants of underreporting. Even though these are potentially modifiable factors through educational interventions, minimal changes have been observed since 2009. Clinical Trials Registration: PROSPERO registration number CRD42021227944. [ABSTRACT FROM AUTHOR]

A potential complication of pharmacotherapy for a given patient is the possibility of various side effects of drugs, which are manifested in many ways and constitute iatrogenic causes of diseases. Among the systemic side effects of drugs, there are also those involving the urinary tract, although these are less reported in the literature. The use of numerous drugs—especially of anticholinergics or drugs with anticholinergic potential, opioid analgesics, non-steroidal anti-inflammatory drugs, antidepressants, first-generation antipsychotics (classic neuroleptics) and selected cardiovascular drugs (beta-blockers, thiazides potassium-sparing diuretics, statins), as well as others—may increase the risk of developing urological disorders, such as urinary retention or incontinence, urinary tract infections, urolithiasis, erectile dysfunction in men and retroperitoneal fibrosis. The purpose of this paper is to characterise the abovementioned drug-induced disorders of the lower urinary tract on the basis of a non-systematic literature review. [ABSTRACT FROM AUTHOR]

Older patients are prone to multimorbidity or related polypharmacy, which may cause various adverse drug reactions (ADRs) and a high incidence of drug‐related health problems. Although not often noted, ADRs include nutrition‐related adverse reactions. Aging, multiple illnesses, mental and psychological problems, declining physical function, and environmental factors can lead to decreased food intake and increased metabolic stress in older people, resulting in energy imbalances that cause malnutrition. ADRs can lead to appetite loss, followed by decreased food intake, which in turn causes malnutrition and deficiencies of various nutrients. However, these nutrition‐related ADRs have received less attention. This review article describes drug–nutrition interactions, with a particular focus on older patients. Geriatr Gerontol Int 2023; 23: 465–477. Pharmacotherapy is a very important means of disease prevention and treatment for older patients. However, adverse drug reactions can have a significant negative impact on the health of older people. In this paper, the impact of drug therapy on nutritional status, dietary intake, the absorption and excretion of nutrients, and metabolism, with a focus on older people, is reviewed. [ABSTRACT FROM AUTHOR]

Medicinal plants or Chinese materia medica (CMM) are now attracting worldwide attention as they have increasingly prominent advantages over chemical drugs in disease treatment and healthcare. Since the 1990s, World Health Organization (WHO) and International Organization for Standardization established the Technical Committee of Traditional Chinese Medicine (ISO/TC 249) have carried out the development of quality standards on medicinal plants or CMMs respectively, and a considerable number of monographs and international standards have been published. Since the two international organizations adhere to different principles, the standards they develop naturally have different emphasis. Driven by market demand and international trade, ISO mainly takes quality, efficacy and safety into consideration when developing standards, while WHO pays more attention to clinical practice, quality control and medication guidance. Up to now, there is a lack of comparative analysis on the records, background, principles, basic content, and main requirements of quality standards on medicinal plants or CMMs respectively published by WHO and ISO. Therefore, based on international standards of CMM developed by ISO/TC 249 platform and WHO Monographs on Selected Medicinal Plants, this paper systematically compares the purposes, selected principles, standard-developing process, basic content, and main quality requirements to summarize their similarities and differences, and find their merits, aiming to serve as a reference to the development of international standards for CMMs that helps them go global. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Chongqing University of Technology (Natural Science) is the property of Chongqing University of Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma but are associated with immune‐related adverse events (irAEs). This single center, cross‐sectional survey aimed to describe the long‐term symptom burden and impact on health‐related quality of life (HRQL) of advanced melanoma patients with sustained disease control following treatment with ICIs. Methods: Advanced melanoma patients (stage IIB, III or IV, AJCCv8), treated with anti‐PD1‐based ICIs, who were off‐treatment and had at least 6 months follow‐up from their last infusion with an ongoing response in the metastatic setting or no evidence of disease recurrence in the adjuvant setting. A paper‐based questionnaire, consisting of the EORTC QLQ‐C30, EORTC QLQ‐FA12, and the PRO‐CTCAE was administered. Results: Of 90 participants, 61 (68%) completed the questionnaire; 40 received single‐agent anti‐PD1, and 21 anti‐PD1/anti‐CTLA4. Thirty‐three (54%) were treated in the adjuvant setting. At the time of enrolment, 31 (51%) participants had active treatment for a previous irAE. Overall, 18/61 (30%) participants reported long‐term symptoms and trouble in physical and emotional functioning. Physical fatigue was common and interfered with daily activities (n = 12, 20%). In the PRO‐CTCAE questionnaire, muscle ache (n = 12, 20%) and joint ache (n = 9, 15%) were commonly reported. Despite this, participants reported overall good health (6.00, range 2.00–7.00) and reasonable level of HRQL (6.00, range 3.00–7.00). Discussion: Melanoma survivors experience long‐term symptoms in physical and psychosocial HRQL domains after ICI treatment. These results underline the importance to address existing gaps in survivorship care, implement these findings in clinical practice and increase awareness for long‐term symptoms in these patients. [ABSTRACT FROM AUTHOR]

Adverse drug reactions (ADRs) are a prominent cause of morbidity and mortality and higher healthcare expenditures. Healthcare professionals (HCPs) play a crucial role in ADR reporting through spontaneous reporting systems, but under-reporting is their major limitation. The goal of this study is to evaluate HCPs' knowledge, attitude, and practice regarding ADR reporting as well as the factors that influence reporting using research papers that are currently available. A literature search was conducted using sources such as PubMed, Scopus, and Google Scholar to find studies that evaluated HCPs' knowledge, attitudes, and practices regarding ADRs reporting in Ethiopia. A standard procedure of systematic review protocol was used to conduct this review. Demographic factors, sample size, response rate, survey delivery, HCP working setting, and encouraging and discouraging factors of ADR reporting were extracted from articles. A total of 17 articles were included in the systematic review out of 384. The number of HCPs in the included studies ranged from 62 to 708. Response rate ranges from 76.1% to 100%. Most of the research included in this evaluation looked at HCPs, who worked in hospitals. When pharmacists were compared to other HCPs, they were more likely to report ADRs; because they had higher knowledge, attitude, and practice. Lack of understanding, unavailability of reporting forms, uncertainty about the causal relationship between the drug and ADR, and failure to report because the ADR was well known were among the common hurdles to ADR reporting identified in research. To improve reporting, educational initiatives and continued training in pharmacovigilance and ADRs are frequently recommended considerations. In Ethiopia, there is a pressing need to close the gap in HCP knowledge, attitudes, and practice regarding PV and ADR reporting. To address this point, specific educational interventions based on existing gaps in ADR reporting should be developed and integrated into the health education curriculum or provided as in-service training after graduation. [ABSTRACT FROM AUTHOR]

PURPOSE: Increasing use of immune checkpoint inhibitors (ICIs) in routine cancer care will increase the incidence of immune-related adverse events (irAEs). Systems are needed to support remote monitoring for irAEs. Electronic patient-reported outcome (ePRO) symptom monitoring systems can help monitor and manage symptoms and side effects. We assessed the content and features of ePRO symptom monitoring systems for irAEs, and their feasibility, acceptability, and impact on patient outcomes and health care utilization. METHODS: A systematic literature search was conducted in May 2022 on MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials. Quantitative and qualitative data relevant to the review questions were extracted and synthesized in tables. RESULTS: Seven papers describing five ePRO systems were included. All systems collected PROs between clinic visits. Two of five used validated symptom questionnaires, 3/5 provided prompts to complete questionnaires, 4/5 provided reminders to self-report, and 3/5 provided clinician alerts for severe/worsening side effects. Four of five provided coverage of ≥26/30 irAEs in the ASCO irAE guideline. Feasibility and acceptability were demonstrated with consent rates of 54%-100%, 17%-27% of questionnaires generating alerts, and adherence rates of 74%-75%. One paper showed a reduction in grade 3-4 irAEs, treatment discontinuation, clinic visit duration, and emergency department presentations, while another showed no difference in these outcomes or the rate of steroid use. CONCLUSION: There is preliminary evidence of the feasibility and acceptability of ePRO symptom monitoring for irAEs. However, further studies are needed to confirm the impact on ICI-specific outcomes, such as the frequency of grade 3-4 irAEs and duration of immunosuppression. Suggestions for the content and features of future ePRO systems for irAEs are provided. [ABSTRACT FROM AUTHOR]

Immunotherapy is widely regarded as a promising treatment for cancer. However, the immune effector phase suppression of tumor microenvironment (TME) and the generation of immune-related adverse events limit its application. Research indicates that sonodynamic therapy (SDT) can effectively activate antitumor immunity while killing tumor cells. SDT produces cytotoxic substances of tumors, and then cell apoptosis and immunogenic death occur by selectively activating the sonosensitizer under ultrasound. In recent years, various SDT alone as well as SDT in combination with other therapies have been developed to induce immunogenic cell death (ICD) and enhance immunotherapy. This paper overviews the research progress of SDT and nanotechnology in recent years, including the strategies involving SDT alone, SDT-based synergistic induction of antitumor immunity, and immunotherapy based on SDT for multimodal immunotherapy. Finally, the prospects and challenges of these SDT-based therapies in cancer immunotherapy are discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Psoriasis is an inflammatory disease associated with important comorbidities that shape a specific clinical frame. Concerns have been expressed in recent decades about the role of systemic inflammation in the promotion of various organ neoplasia. Moreover, psoriasis treatment is chronic, usually lifelong, and uses various classes of drugs, of which some have an intrinsic effect on the body's cancer-control mechanisms. While in other works we studied the correlation between psoriasis, its treatment, and organ cancers, this paper is a review of available data that evaluate the connection and intricate risk of skin cancer in psoriatic patients. Good knowledge of these risks might help both the patient and the care provider to avoid the development of skin neoplasia in selected patients. Psoriasis is a common chronic, immune-mediated, inflammatory disease with associated comorbidities. Common psoriasis-associated comorbidities include psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory digestive syndromes, and depression. A less studied association is between psoriasis and specific-site cancers. A key cell in the pathophysiology of psoriasis is the myeloid dendritic cell, which links the innate and adaptive immune systems, and therefore is involved in the control of cancer-prevention mechanisms. The relationship between cancer and inflammation is not new, with inflammation being recognized as a key element in the development of neoplastic foci. Infection leads to the development of local chronic inflammation, which further leads to the accumulation of inflammatory cells. Various phagocytes produce reactive oxygen species that cause mutations in cellular DNA and lead to the perpetuation of cells with altered genomes. Therefore, in inflammatory sites, there will be a multiplication of cells with damaged DNA, leading to tumor cells. Over the years, scientists have tried to assess the extent to which psoriasis can increase the risk of developing skin cancer. Our aim is to review the available data and present some information that might help both the patients and the care providers in properly managing psoriatic patients to prevent skin cancer development. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are frequently utilized for the treatment of a range of stomach disorders, but like any medication, they can cause adverse reactions. The benefits of taking these drugs generally outweigh the risks, but Potential adverse effects should be taken into consideration. This review will present updated information on the negative reactions associated with PPIs and identify areas for further research. The research for this paper was gathered from a variety of sources, including Google Scholar, Science Direct, PubMed and other journals published between 1998 and 2022. [ABSTRACT FROM AUTHOR]

Copyright of Farmacia is the property of Societatea de Stiinte Farmaceutice Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

2022; 88 (12): 4985 - 4996. doi: 10.1111/bcp.15571 6 Aurich B, Apele-Freimane D, Banaschewski T, et al. c4c: Paediatric pharmacovigilance: methodological considerations in research and development of medicines for children - a c4c expert group white paper. At the same time almost half of these prescriptions are off-label, due to a historical lack of medicines specifically developed for children.1 For ethical, practical and economic reasons, academic and industry researchers were reluctant to study drugs in children. On average, half of all children in Europe take medicines, either for acute or chronic illness. [Extracted from the article]

Copyright of Przegląd Elektrotechniczny is the property of Przeglad Elektrotechniczny and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Adverse drug reactions (ADRs) are increasingly becoming a serious public health problem. Spontaneous reporting systems (SRSs) are an important way for many countries to monitor ADRs produced in the clinical use of drugs, and they are the main data source for ADR signal detection. The traditional signal detection methods are based on disproportionality analysis (DPA) and lack the application of data mining technology. In this paper, we selected the spontaneous reports from 2011 to 2018 in Jiangsu Province of China as the research data and used association rules analysis (ARA) to mine signals. We defined some important metrics of the ARA according to the two-dimensional contingency table of ADRs, such as Confidence and Lift, and constructed performance evaluation indicators such as Precision, Recall, and F1 as objective standards. We used experimental methods based on data to objectively determine the optimal thresholds of the corresponding metrics, which, in the best case, are Confidence = 0.007 and Lift = 1. We obtained the average performance of the method through 10-fold cross-validation. The experimental results showed that F1 increased from 31.43% in the MHRA method to 40.38% in the ARA method; this was a significant improvement. To reduce drug risk and provide decision making for drug safety, more data mining methods need to be introduced and applied to ADR signal detection. [ABSTRACT FROM AUTHOR]