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This document is a compilation of articles and reviews on the treatment and management of osteoradionecrosis and medication-related osteonecrosis of the jaw (MRONJ). It includes systematic reviews, position papers, and studies discussing various treatment protocols, risk factors, and complications associated with these conditions. The articles provide insights from specialists in bone metabolism and maxillofacial specialists, offering a comprehensive perspective on the topic. The document also addresses the use of specific medications, such as pentoxifylline, tocopherol, clodronate, and denosumab, in the treatment and prevention of osteonecrosis. [Extracted from the article]

Background Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. Materials and Methods In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. Results As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. Conclusion Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications. Clinicaltrials.gov ID NCT03517449 [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the mental health information entities and associations between the biomedical, psychological and social domains of bipolar disorder (BD) by analyzing social media data and scientific literature. Design/methodology/approach: Reddit posts and full-text papers from PubMed Central (PMC) were collected. The text analysis was used to create a psychological dictionary. The text mining tools were applied to extract BD entities and their relationships in the datasets using a dictionary- and rule-based approach. Lastly, social network analysis and visualization were employed to view the associations. Findings: Mental health information on the drug side effects entity was detected frequently in both datasets. In the affective category, the most frequent entities were "depressed" and "severe" in the social media and PMC data, respectively. The social and personal concerns entities that related to friends, family, self-attitude and economy were found repeatedly in the Reddit data. The relationships between the biomedical and psychological processes, "afraid" and "Lithium" and "schizophrenia" and "suicidal," were identified often in the social media and PMC data, respectively. Originality/value: Mental health information has been increasingly sought-after, and BD is a mental illness with complicated factors in the clinical picture. This paper has made an original contribution to comprehending the biological, psychological and social factors of BD. Importantly, these results have highlighted the benefit of mental health informatics that can be analyzed in the laboratory and social media domains. [ABSTRACT FROM AUTHOR]

Background/aims: Serious adverse event reporting guidelines have largely been developed for pharmaceutical trials. There is evidence that serious adverse events, such as psychological distress, can also occur in non-pharmaceutical trials. Managing serious adverse event reporting and monitoring in palliative care non-pharmaceutical trials can be particularly challenging. This is because patients living with advanced malignant or non-malignant disease have a high risk of hospitalisation and/or death as a result of progression of their disease rather than due to the trial intervention or procedures. This paper presents a number of recommendations for managing serious adverse event reporting that are drawn from two palliative care non-pharmacological trials. Methods: The recommendations were iteratively developed across a number of exemplar trials. This included examining national and international safety reporting guidance, reviewing serious adverse event reporting procedures from other pharmacological and non-pharmacological trials, a review of the literature and collaboration between the ACTION study team and Data Safety Monitoring Committee. These two groups included expertise in oncology, palliative care, statistics and medical ethics and this collaboration led to the development of serious adverse event reporting procedures. Results: The recommendations included; allowing adequate time at the study planning stage to develop serious adverse event reporting procedures, especially in multi-national studies or research naïve settings; reviewing the level of trial oversight required; defining what a serious adverse event is in your trial based on your study population; development and implementation of standard operating procedures and training; refining the reporting procedures during the trial if necessary and publishing serious adverse events in findings papers. Conclusions: There is a need for researchers to share their experiences of managing this challenging aspect of trial conduct. This will ensure that the processes for managing serious adverse event reporting are continually refined and improved so optimising patient safety. Trial registration: ACTION trial registration number: ISRCTN63110516 (date of registration 03/10/2014). Namaste trial registration number: ISRCTN14948133 (date of registration 04/10/2017). [ABSTRACT FROM AUTHOR]

Background: Underreporting is the major limitation of a voluntary adverse drug reaction (ADR) reporting system. Many studies have assessed the effectiveness of different interventions designed to reduce underreporting. Objective: We aimed to conduct a critical review of papers that assessed the effectiveness of different strategies to increase ADR reporting, regardless of the health professionals or patients included. Data Sources: Scientific papers were selected after a search of the MEDLINE-PubMed and EMBASE scientific databases up to 7 December 2010. Study Selection: We included papers in English, French or Spanish that analysed an intervention aimed at increasing the number of reported ADRs, and quantify the results of the intervention in terms of number of reports. Data Extraction: The abstracts retrieved in both computerized searches were reviewed independently by two of the authors. Initially selected papers were thoroughly read to evaluate if they met inclusion and exclusion criteria. Data in finally selected papers were independently extracted by both authors and set in pre-designed tables. A third author took the final decision in case of disagreement. For each study, we analysed study design, type of intervention, assessment period, and results of the intervention. Results: Of the 4,221 papers located that fulfilled the search criteria, 43 met the selection criteria. With the exception of one study, the interventions assessed were deemed to be effective. The vast majority of papers displayed methodological and formal limitations that lowered the grade of evidence. Multiple interventions seem to have had more impact than did single interventions. There were very few cases in which interventions were designed on the basis of inappropriate attitudes and mistaken beliefs about ADRs. Conclusions: In general, there is a need for studies of better methodological quality in this topic, so that more evidence of the effectiveness of the respective strategies can be collected for the purpose of improving ADR reporting by health professionals. It is probable that multiple interventions cause greater increases in the ADR reporting rates than single. [ABSTRACT FROM AUTHOR]

The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on cardiovascular risk factors as a singular entity or on organ-specific HTN. Furthermore, available studies reporting findings on drug-induced HTN in MPNs report varying and contradictory findings. In consideration of the above, this study set out to systematically review the available literature and shed light on the occurrence of HTN in MPNs, its association with thrombosis, as well as the drugs used in MPN management that could increase blood pressure. The literature search yielded 598 potentially relevant records of which 315 remained after the duplicates (n = 283) were removed. After we screened the titles and the abstracts of these publications, we removed irrelevant papers (n = 228) and evaluated the full texts of 87 papers. Furthermore, 13 records did not meet the inclusion criteria and were excluded from the systematic review. Finally, a total of 74 manuscripts were entered into the qualitative synthesis and included in the present systematic review. Our systematic review highlights that HTN is the most common comorbidity encountered in MPNs, with an impact on both the occurrence of thrombosis and survival. Moreover, drug-induced HTN remains a challenge in the management of MPNs. Further research should investigate the characteristics of patients with MPNs and HTN, as well as clarify the contribution of HTN to the development of thrombotic complications, survival and management in MPNs. In addition, the relationship between clonal hematopoiesis of indeterminate potential, HTN, cardiovascular disease and MPNs requires examination in upcoming assessments. [ABSTRACT FROM AUTHOR]

Purpose: Coronavirus disease-2019 (COVID-19) is becoming a crucial health problem worldwide. Continued and high-speed mutations of this virus result in the appearance of new manifestations, making the control of this disease difficult. It has been shown that well-nourished patients have strong immune systems who mostly have short-term hospitalization compared to others. The purpose of this study is to review the major nutrients involved in the immune system reinforcement and to explain nutritional aspects during the recovery of COVID-19. Design/methodology/approach: In this review paper, the mechanistic role of nutrients in boosting the immune system and the nutritional aspects during the recovery of COVID-19 patients were discussed. Papers indexed in scientific databases were searched using antioxidants, COVID-19, inflammation, immune system, macronutrient, micronutrient and probiotic as keywords from 2000 to 2022. Findings: Because of the adverse effects of drugs like thrombosis, pulmonary embolism and hypercholesterolemia, a balanced diet with enough concentrations of energy and macronutrients could increase the patient's durability. The inflammatory cytokines in a vicious cycle delay patients' rehabilitation. The main mechanistic roles of micronutrients are attributed to the downregulation of virus replication and are involved in energy homeostasis. Dysbiosis is defined as another disturbance among COVID-19 patients, and supplementation with beneficial strains of probiotics helps to exert anti-inflammatory effects in this regard. Being on a well-planned diet with anti-inflammatory properties could reverse cytokine storms as the major feature of COVID-19. Future studies are needed to determine the safe and effective dose of dietary factors to control the COVID-19 patients. Originality/value: Being on a well-planned diet with anti-inflammatory properties could reverse cytokine storms as the major feature of COVID-19. Future studies are needed to determine the safe and effective dose of dietary factors to control the COVID-19 patients. [ABSTRACT FROM AUTHOR]

Doping is a public health issue and not simply a problem inside the professional sports community It is a complex and ancient phenomenon considering the vast variety of substances, supplied through both legal and illegal trading routes. It occurs in elite athletes but also affects amateur athletes and was generally considered as dangerous and unhealthy. Furthermore, it involves athletes' friends and relatives, medical staff, managers, chemists, biologists and pharmacists, pharmaceutical industries, clandestine laboratories and criminal organizations. Over time, doping has shown a great ability to discover and always use new substances and appropriated the new scientific discoveries. Unfortunately, new discoveries for the human health have been used in distorted way by the athletes. In fact, the athletes may be able to use gene therapy to re-engineer their bodies for better performances. Drug dependence depends on several factors: the socio-environmental context of the subject and what effects have the substance in the body. We will agree that sport is essentially under the current anti-doping campaign executed by a coordinated alliance between the World Anti-Doping Agency (WADA), law enforcement authorities, sports organizers and the media. This paper explores comprehensive description of the state of doping and its regulation in the past and nowadays. [ABSTRACT FROM AUTHOR]

The article focuses on the lack of proper medication for the treatment of spinal cord injury associated spasticity. It mentions that the drug baclofen which is a derivative of a gamma-aminobutyric acid, is usually prescribed to the patients with spinal cord injury, it, however leads to harmful side affects in patients including excessive drowsiness. .Before baclofen, cyproheptadine drug was used but it is no longer in use because it could lead to increased food intake and weight gain.

Immunotherapy has been used extensively for 80 years as a specific treatment of allergy. In the last decade, the clinical practice of immunotherapy has changed markedly in certain parts of Europe. In southern Europe immunotherapy still represents the cornerstone of allergy treatment, while in Scandinavia and Great Britain a large number of allergic patients receive immunotherapy. In spite of the fact that a large number of recently published, wee-performed clinical trials have documented the evidently beneficial effect of immunotherapy, the decrease is probably caused by a combination of some degree of uncertainty as to the clinical efficacy, the risk of side effects, and the introduction of potent new drugs for prophylactic treatment of allergic diseases. With the overall aim of improving the safety of immunotherapy and making it more convenient to patients, routes other than the subcutaneous administration of allergens have been investigated.

The article presents abstracts on dentistry which include oral health, adverse drug interactions in dentistry and lysine decarboxylase in gingivitis.

This article presents information on a study, published in the August 25, 2005, issue of the journal "Annals of Neurology," which reported an incident of cerebral edema in an 80-year-old woman following abrupt withdrawal from pregabalin. Pregabalin, reportedly, is an antiepileptic drug made by Pfizer Inc. under the brand name "Lyrica." The woman, suffering from severe pain associated with shingles, was taking part in a clinical trial of Lyrica. Within a week after terminating the drug, she experienced delirium and hallucinations, and a magnetic resonance imaging report revealed swelling similar to that seen in epileptic patients who abruptly stop their drugs.

The article focuses on therapeutic targets and scientific progress toward the development of appropriate animal models by utilizing novel strategies that will help in understanding the pathogenesis and pathophysiology of anorexigen-induced valvulopathy and pulmonary arterial hypertension (PAH). According to the author, various safety issues, such as valvulopathy with fenfluramine and PAH with aminorex, were initially not predicted by routine preclinical toxicology studies. The author also discusses the translatability challenges of drug effects from animals to humans.

Tracking devices have become small enough to be widely applied to arthropods to study their movement. However, possible side effects of these devices on arthropod performance and behaviour are rarely considered.We performed a systematic review of 173 papers about research in which tracking devices—radio frequency identification (RFID), harmonic radar and radio telemetry tags—were attached to terrestrial arthropods. The impact of such tags was quantified in only 12% of the papers, while in 40% the potential impact was completely disregarded. Often‐cited rules of thumb for determining appropriate tag weight had either no empirical basis or were misconstrued.Several properties of a tracking device (e.g. weight, balance, size, drag) can affect different aspects of an arthropod's life history (e.g. energy, movement, foraging, mating). The impact can differ among species and environments. Taken together, these tag effects can influence the reliability of obtained movement data and conclusions drawn from them. We argue that the impact of tracking devices on arthropods should be quantified for each (a) study species, (b) tag type, and (c) environmental context. As an example, we include a low‐effort impact study of the effect of an RFID tag on a digger wasp.Technological advancements enable studying the movement of arthropods in unprecedented detail. However, we should adopt a more critical attitude towards the use of tracking devices on terrestrial arthropods. The benefits of tracking devices should be balanced against their potential side effects on arthropods and on the reliability of the resulting data. [ABSTRACT FROM AUTHOR]

Objective: Describe and synthesise existing published research on the experiences and support needs of informal caregivers of people with multimorbidity. Design: Scoping literature review. Primary database and secondary searches for qualitative and/or quantitative English-language research with an explicit focus on informal carers of people with multimorbidity (no date restrictions). Quality appraisal of included papers. Thematic analysis to identify key themes in the findings of included papers. Results: Thirty-four papers (reporting on 27 studies) were eligible for inclusion, the majority of which were rated good quality, and almost half of which were published from 2015 onwards. The review highlights common difficulties for informal carers of people with multiple chronic illnesses, including practical challenges related to managing multiple health care teams, appointments, medications and side effects, and psychosocial challenges including high levels of psychological symptomatology and reduced social connectedness. Current gaps in the literature include very few studies of interventions which may help support this caregiver group. Conclusion: Interest in this research area is burgeoning. Future work might fruitfully examine the potential benefits of audio-recorded health care consultations, and digitally delivered psychosocial interventions such as online peer support forums, for supporting and enhancing the caring activities and wellbeing of this caregiver group. [ABSTRACT FROM AUTHOR]

Purpose: The present scoping review aims to assess the non-inferiority of distributed learning over centrally and locally trained machine learning (ML) models in medical applications. Methods: We performed a literature search using the term "distributed learning" OR "federated learning" in the PubMed/MEDLINE and EMBASE databases. No start date limit was used, and the search was extended until July 21, 2020. We excluded articles outside the field of interest; guidelines or expert opinion, review articles and meta-analyses, editorials, letters or commentaries, and conference abstracts; articles not in the English language; and studies not using medical data. Selected studies were classified and analysed according to their aim(s). Results: We included 26 papers aimed at predicting one or more outcomes: namely risk, diagnosis, prognosis, and treatment side effect/adverse drug reaction. Distributed learning was compared to centralized or localized training in 21/26 and 14/26 selected papers, respectively. Regardless of the aim, the type of input, the method, and the classifier, distributed learning performed close to centralized training, but two experiments focused on diagnosis. In all but 2 cases, distributed learning outperformed locally trained models. Conclusion: Distributed learning resulted in a reliable strategy for model development; indeed, it performed equally to models trained on centralized datasets. Sensitive data can get preserved since they are not shared for model development. Distributed learning constitutes a promising solution for ML-based research and practice since large, diverse datasets are crucial for success. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to estimate the incidence of cardiac immune‐related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs). Methods and results: First, we performed an ICI pharmacovigilance analysis, finding 4.2% of cardiac disorders, including myocarditis, for anti‐CTLA‐4, anti‐PD‐1, and anti‐PD‐L1 therapies. Patients treated with anti‐PD‐1 antibodies presented a greater number of cardiac adverse events (AEs) than those treated with anti‐CTLA‐4 (69.4% vs. 20%). Then, we analysed the incidence and characteristics of cardiac irAEs in 1265 papers published prior to 31 August 2020. Of the 4751 patients studied, 1.3% presented cardiac irAEs, with myocarditis being the most frequent (50.8%); 15 patients died (24.6%) due to cardiac irAEs. Finally, we conducted a meta‐analysis to determine cardiac irAEs in randomized clinical trials, identified through a systematic search from the ClinicalTrials.gov database, finding an incidence of 3.1% for ICI monotherapies, 5.8% for dual ICI therapies, 3.7% (irAEs/AEs) for ICIs plus chemotherapy, and cardiac AEs were reported in 2.5% of patients treated solely with chemotherapy. Conclusions: Our study provides precise data for the incidence of cardiac irAEs among patients using ICIs, where despite its low incidence, the high rate of mortality is an important issue to consider. ICIs induce mainly myocarditis at the first doses, and dual therapies seem to provoke higher rates of cardiac irAEs than monotherapies or ICIs plus chemotherapy. [ABSTRACT FROM AUTHOR]

Figures from the Editor's selected issue highlights will be displayed each month in the journal image carousel on the BJCP homepage http://bpspubs.onlinelibrary.wiley.com/hub/journal/10.1111/(ISSN)1365-2125/ You will really like this issue of the Br J Clin Pharmacology! In the third paper Gerd Mikus, from Heidelberg, Germany, describes a micro-dosed cocktail of three DOACs that can be used to identify drug-drug interactions. Stefan Weisshaar I et al i . from Vienna, Austria, are actively fighting this other epidemic and investigated the clinical effects of various dose ratios of morphine and naloxone in OUD patients. [Extracted from the article]

Simple Summary: Malignant neoplasms are currently one of the main causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in cancer biology and immunity research have led to the development of immunotherapy, which is now used in routine clinical practice in cancer treatment. Along with the increasing number of patients treated with immunotherapy, a wider spectrum of side effects, called immune-related adverse events, have been brought to light. Most of them have a mild or moderate manifestation. However, in rare cases of life-threatening symptoms, proper and rapid management is of utmost importance. In this review, we focus on life-threatening endocrine side effects of immunotherapy to provide information on the symptoms, diagnostics, and management strategies described in the literature to date. Malignant neoplasms are currently one of the leading causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in research in cancer biology and immunity have led to the development of immunotherapy, which is now used on an everyday basis in cancer treatment in addition to surgical treatment, classical cytostatics, and radiotherapy. The efficacy of immunotherapy has promoted the great popularity of this treatment among patients, as well as significant research interest. The increasing number of patients being treated with immunotherapy not only reassures physicians of the efficacy of this technique but also shows the wide spectrum of side effects of this therapy, which has not been considered before. Immune-related adverse events may affect many systems and organs, such as digestive, cardiovascular, respiratory, skin, or endocrine organs. Most complications have a mild or moderate course, but there are life-threatening manifestations that are essential to be aware of because if they are not properly diagnosed and treated on time, they can have fatal consequences. The purpose of this paper was to present the results of a literature review on the current state of knowledge on life-threatening endocrine side effects (such as adrenal crisis, thyroid storm, myxoedema crisis, diabetic ketoacidosis, and severe hypocalcaemia) of immune checkpoint inhibitors to provide information on symptoms, diagnostics, and management strategies. [ABSTRACT FROM AUTHOR]

Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of the antidote acetylcysteine linked to new methods of risk assessment transformed the treatment of this poisoning. This review will describe the way in which risk assessment and treatments have developed over the last 50 years and highlight the remaining areas of uncertainty. A search of PubMed and its subsidiary databases revealed 1,166 references published in the period 1963–2023 using the combined terms "paracetamol", "poisoning", and "acetylcysteine". Focused searches then identified 170 papers dealing with risk assessment of paracetamol poisoning, 141 with adverse reactions to acetylcysteine and 114 describing different acetylcysteine regimens. To manage the extensive literature, we focused mainly on contributions made by the authors during their time in Edinburgh and Denver. The key relationship between paracetamol dose and toxicity risk was established in 1971 and led to the development of the Rumack-Matthew nomogram from data collected in Edinburgh. A series of papers on the mechanisms of toxicity were published in 1973, and these showed that paracetamol hepatotoxicity was caused by the formation of a toxic intermediate epoxide metabolite normally detoxified by glutathione but which, in excess, was bound covalently to hepatic enzymes and proteins. An understanding of the relationship between the rate of paracetamol metabolism, paracetamol concentration, and toxic hazard in humans soon followed. These discoveries were followed by the testing of a range of sulfhydryl-donors in animals and "at risk" patients. Acetylcysteine was developed as the lead intravenous antidote in the United Kingdom. The license holder in the United States refused to make an intravenous formulation. Thus, oral acetylcysteine became the antidote trialed in the United States National Multicenter Study. Intravenous acetylcysteine regimens used initially in the United Kingdom and subsequently in the United States used loading doses of 150 mg/kg over 15 minutes or one hour, 50 mg/kg over four hours, and 100 mg/kg over 16 hours. These regimens were associated with adverse drug reactions (nausea, vomiting and anaphylactoid reactions) and hence, treatment interruption. Newer dosing regimens now give loading doses more slowly. One, the Scottish and Newcastle Anti-emetic Pretreatment protocol, using an acetylcysteine regimen of 100 mg/kg over two hours followed by 200 mg/kg over 10 hours, has been widely adopted in the United Kingdom. A cohort comparison study suggests this regimen has comparable efficacy to standard regimens and offers opportunities for selective higher acetylcysteine dosing. No dose-ranging studies with acetylcysteine were done, and no placebo-controlled studies were performed. Thus, there is uncertainty regarding the optimal dose of acetylcysteine, particularly in patients ingesting very large overdoses of paracetamol. The choice of intervention concentration on the Rumack-Matthew nomogram has important consequences for the proportion of patients treated. The United States National Multicenter Study used a "treatment" line starting at 150 mg/L (992 µmol/L) at 4 hours post overdose, extending to 24 hours with a half-life of 4 hours, now standard there, and subsequently adopted in Australia and New Zealand. In the United Kingdom, the treatment line was initially 200 mg/L (1,323 µmol/L) at 4 hours (the Rumack-Matthew "risk" line). In 2012, the United Kingdom Medicines and Healthcare products Regulatory Agency lowered the treatment line to 100 mg/L (662 µmol/L) at 4 hours for all patients, increasing the number of patients admitted and treated at a high cost. Risk assessment is a key issue for ongoing study, particularly following the development of potential new antidotes that may act in those at greatest risk. The development of biomarkers to assess risk is ongoing but has yet to reach clinical trials. Even after 50 years, there are still areas of uncertainty. These include appropriate acetylcysteine doses in patients who ingest different paracetamol doses or multiple (staggered) ingestions, early identification of at-risk patients, and optimal treatment of late presenters. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular disorders (TMD) are the main cause of chronic facial pain, and intra‐articular (IA) injections of hyaluronic acid (HA) are commonly performed. Objectives: This umbrella review of systematic reviews aimed at analysing the effectiveness of HA injections on pain and functional outcomes in patients affected by TMD. Methods: PubMed, Cochrane Library and PEDro were systematically searched from inception until 17 January 2023 to identify systematic reviews evaluating the effects on pain and functional outcomes of HA IA injections. PROSPERO registration number: CRD42022382586. Results: Out of 316 papers suitable for title/abstract screening, 18 articles were included in the umbrella review. Thirteen studies included only randomized controlled clinical trials (RCTs). The included systematic reviews reported no statistically significant differences between HA and corticosteroids, whereas platelet derivates seem to have good results in pain relief. The literature did not show severe adverse events, except for mild pain in the site of injection. Concerning the quality assessment of the 18 systematic reviews, 2 (11.11%) had a high quality, 3 (16.67%) a moderate quality, 7 (38.89%) a low quality and 6 (33.33%) a critically low quality. Conclusions: Taken together, findings of this umbrella review showed intriguing effects of IA HA injections in terms of reduction of pain intensity and improvement of functioning in patients affected by TMD. Furthermore, there is no agreement on the effectiveness of a combination of arthrocentesis or arthroscopy with IA HA injections. Although the literature showed these positive results after IA HA injections, the overlapping of primary studies in the systematic reviews included might have affect our results, such as the very low quality of the papers. Thus, further RCTs are needed to confirm the efficacy of IA injections of HA on pain relief in patients with TMD. [ABSTRACT FROM AUTHOR]

Drug overdose claimed more than 100,000 lives in the United States in 2021. Drug‐induced homicide (DIH) laws create specific criminal liability for individuals who provide drugs that cause or contribute to the death of another person. DIH prosecutions in the United States have increased substantially over the past decade despite the absence of meaningful evidence of their individual‐ or community‐level impacts. Recently, Lee et al. analyzed the impact of DIH laws on county‐level opioid overdose mortality across 92 counties in 10 states and concluded that DIH laws are associated with significant reductions in rates of opioid overdose death. In this commentary, we present evidence demonstrating that the Lee et al. study is fundamentally flawed. Specifically, the legal data used by Lee et al. to define their treatment condition (the presence or absence of a state‐level DIH law) is incorrect in almost every aspect. We also describe significant methodological weaknesses, including flawed sampling strategies that resulted in a biased sample of county overdose rates as well as flawed modeling strategies that cannot effectively evaluate the hypothesis that DIH laws negatively impact opioid overdose mortality. More research on the individual‐ and community‐level impacts of DIH laws is needed. In the meantime, we advise policymakers to strengthen state 911 Good Samaritan laws, as DIH laws appear to erode the efficacy of this proven overdose‐prevention strategy. Key points: Drug‐induced homicide laws create specific criminal liability for individuals who provide drugs that cause or contribute to the death of another person and are increasingly used in the United States despite little evidence of their impact on overdose and other harms.This paper critically evaluates a recent paper that analyzed the impact of these laws on county‐level opioid overdose mortality across 92 counties in 10 US states, concluding that these laws are associated with reduced opioid overdose deaths.We present evidence demonstrating that the previous paper is fundamentally flawed, detailing serious errors in the underlying legal research as well as significant methodological weaknesses that render the results of the paper unreliable.Reliable research on the impact of these laws is urgently needed. In the meantime, policymakers are urged to implement policies with robust evidence demonstrating their overdose‐prevention impacts: medications for opioid use disorder, naloxone access, and syringe services programs. [ABSTRACT FROM AUTHOR]

Background: This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs. Methods: We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published. Results: A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone. Conclusion: Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients. [ABSTRACT FROM AUTHOR]

Introduction: Drug treatment can be related to the development of adverse drug reactions (ADRs). Aim: In this paper, we evaluated ADRs in patients admitted to the Ambulatory of Pain Medicine of the University Hospital Renato Dulbecco in Catanzaro. Methods: We conducted a prospective analysis between 1 February 2021 and 20 July 2023 on patients with neuropathic pain referred to the Ambulatory of Pain Medicine of "Renato Dulbecco" University Hospital in Catanzaro (Calabria, Italy). Patients aged >18 years with clinical signs of neurologic pain and a score upon completing the Douleur Neuropathique en 4 Questions (DN4) questionnaire of ≥4 were included. The association between drugs and ADR or between drugs and drug–drug-interactions (DDIs) was evaluated using Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. Results: During the study period, we analyzed 2370 patients referred to the ambulatory of pain medicine. After the evaluation of inclusion and exclusion criteria, 33.5% of patients were enrolled. All patients presented at least one comorbidity and daily used a mean of five drugs (range 3–11). Using the Naranjo score, the development of ADRs was documented in 112 patients (score 6). Using parametric and non-parametric statistical analysis, we failed to report an association between ADR and dosage or ADR and patient characteristics. Conclusion: Our results show the development of ADRs in 18% of patients with neuropathic pain. This low percentage of drug interaction could be a limitation in real life because it is probably due to the site of the study and the appropriate prescription of drugs. Therefore, it shows that it is necessary to motivate healthcare to pay attention to the prescription of drugs in poly-treated patients to reduce the risk of ADRs. [ABSTRACT FROM AUTHOR]

The use of immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in the treatment of various malignancies, significantly reshaping cancer treatment. However, as a result of the widespread use of ICIs, several immune-related adverse events (iRAEs) have emerged, some of which can be rare and potentially fatal. In this paper, we reported the earliest case of Sintilimab used in the treatment of esophageal cancer with severe inflammatory myopathy (involving the cardiac, respiratory, and skeletal muscles)in China. This patient was an elderly female who presented to our institution with progressive limb weakness and ptosis. Prior to the onset of symptoms, the patient had undergone a radical esophagectomy for esophageal cancer, experienced several cycles of of radiotherapy and chemotherapy, as well as two doses of Sintilimab treatment. Shortly after initiating immunotherapy, the patient developed symptoms including bilateral ptosis, limb weakness, and difficulty swallowing and breathing. The levels of creatine kinase and troponin I in the patient's blood were significantly elevated, and positive results were observed for anti-skeletal and anti-cardiac muscle antibodies, indicating that the patient might be developing ICIs-related inflammatory myopathy. Fortunately, the patient responded well to treatment including corticosteroids, plasmapheresis, intravenous immunoglobulin, and other supportive therapies. Here, we discuss the incidence, mechanisms, and management strategies of fatal iRAEs. Early detection and timely intervention may be critical in reducing the incidence and mortality rates of iRAEs and improving patient outcomes. [ABSTRACT FROM AUTHOR]

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Omadacycline is a novel tetracycline antibiotic that exhibits good in vitro antibacterial activity against atypical pathogens such as Mycoplasma pneumoniae. It is approved for the treatment of adults with communityacquired bacterial pneumonia. However, the safety and efficacy of omadacycline in pediatric patients under 18 years of age have not yet been established. In the present paper, we report a case of pediatric communityacquired pneumonia in which initial empirical anti-infective therapy had failed. The patient received empirical anti-infective therapy with azithromycin and other antimicrobial agents upon admission but showed a poor clinical response and developed secondary tinnitus and liver dysfunction. After the confirmation of M. pneumoniae infection through metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid, an antibiotic switch to omadacycline was made. Thereafter, the patient's condition improved, and no adverse reactions were observed. These findings demonstrate that mNGS enables the identification of infection-causing pathogens in patients with unresponsive pneumonia. Omadacycline can be considered as an alternative option for antiinfective therapy in pediatric M. pneumoniae pneumonia, especially when the presence of bacterial resistance, adverse drug reactions, or organ failure are taken into consideration. [ABSTRACT FROM AUTHOR]

Traditional remedies have gained recognition for their effectiveness in treating various conditions such as diabetes, arthritic pain, liver disease, cough and cold, memory enhancement, and immunological stimulation. Their perceived safety has led to the increasing use of herbs by people without prescriptions. These therapies remain significant in areas with limited access to modern drugs or cultural preferences for traditional treatments. With a long history of use, traditional medicines have been the primary method of pain management. This review article explores natural and herb-based analgesics, their origins, and potential benefits, along with the growing scientific evidence supporting their effectiveness. Studies have examined their efficacy in treating musculoskeletal pain, neuropathic pain, and migraines. Rather than being seen as separate therapies, traditional medicines should be considered supplementary or alternative options that can be integrated into comprehensive pain management regimens. However, some studies have reported adverse drug reactions associated with herbal formulations and plants. Therefore, there is a need for pharmacovigilance in traditional medicine to ensure patient safety and promote evidence-based practices. Although pharmacovigilance in this field is still developing, it faces challenges due to the wide availability of herbal medicines without on-site medical supervision. This paper discusses the complex challenges of herbal pharmacovigilance, provides insights on recent advancements, and offers recommendations for improving the safety monitoring of traditional medications in the future. [ABSTRACT FROM AUTHOR]

Background: Post-intensive care syndrome (PICS) is defined as a new or worsening impairment in physical, cognitive, or mental health following critical illness. Intensive care unit recovery centers (ICU-RC) are one means to treat patients who have PICS. The purpose of this study is to describe the role of pharmacists in ICU-RCs. Research Question: What is the number and type of medication interventions made by a pharmacist at an ICU-RC at 12 different centers? Study Design and Methods: This prospective, observational study was conducted in 12 intensive care units (ICUs)/ICU-RCs between September 2019 and July 2021. A full medication review was conducted by a pharmacist on patients seen at the ICU-RC. Results: 507 patients were referred to the ICU-RC. Of these patients, 474 attended the ICU-RC and 472 had a full medication review performed by a pharmacist. Baseline demographic and hospital course data were obtained from the electronic health record and at the ICU-RC appointment. Pharmacy interventions were made in 397 (84%) patients. The median number of pharmacy interventions per patient was 2 (interquartile range [IQR] = 1,3). Medications were stopped and started in 124 (26%) and 91 (19%) patients, respectively. The number of patients that had a dose decreased and a dose increased was 51 (11%) and 43 (9%), respectively. There was no difference in the median total number of medications that the patient was prescribed at the start and end of the patient visit (10, IQR = 5, 15). Adverse drug event (ADE) preventive measures were implemented in 115 (24%) patients. ADE events were identified in 69 (15%) patients. Medication interactions were identified in 30 (6%) patients. Interpretation: A pharmacist plays an integral role in an ICU-RC resulting in the identification, prevention, and treatment of medication-related problems. This paper should serve as a call to action on the importance of the inclusion of a pharmacist in ICU-RC clinics. [ABSTRACT FROM AUTHOR]

Background: Hemovigilance is an important aspect of transfusion medicine. However, the frequency of the adverse reactions often varies using different reporters. Recently, we have employed a new information technology (IT)-based in-hospital hemovigilance system. Here, we evaluated changes in practice after implementation of an IT-based reporting system.Study Design and Methods: We compared the rate of frequency and details of blood transfusion-related adverse reactions 3 years before and after introduction of the IT-based reporting system. Contents and severity of the adverse reactions were reported in a paper-based reporting system, but input by selecting items in an IT-based reporting system. The details of adverse reactions are immediately sent to the blood transfusion unit online.Results: After we introduced the IT-based reporting system, the reported rate of transfusion-related adverse reactions increased approximately 10-fold from 0.20% to 2.18% (p < 0.001), and frequencies of urticaria, pruritus, rash, fever (p < 0.001), hypertension (p = 0.001), tachycardia (p = 0.003), and nausea and vomiting (p = 0.010) increased significantly. Although there was no error report in the paper-based reporting, incorrect reports were observed in 90 cases (0.52%) in the IT-based reporting (p < 0.001).Conclusion: The advantages of IT-based reporting were: 1) a significant increase in the frequency of adverse reaction reporting and 2) a significant decrease in underreporting, although the true frequency has yet to be clarified. The disadvantage of the IT-based reporting was an increased incidence of incorrect inputs, all of which was unnoticed by the reporters. Our results showed several important points in need of monitoring after introduction of an IT-based reporting system. [ABSTRACT FROM AUTHOR]

Intranasal (IN) medications offer a safe non-invasive way to rapidly deliver drugs in situations where intravenous (IV) access and intramuscular (IM) administration is challenging or not feasible. In the prehospital setting, this can be an essential alternative in time critical situations including trauma management, seizures, and agitated patients. However, there is a paucity of evidence summarizing its efficacy in this environment. This systematic review aims to assess the current evidence supporting the use of IN medicine (midazolam, ketamine, fentanyl, morphine, glucagon, and naloxone) in the prehospital setting alone. A systematic literature search (PROSPERO CRD42023440713) of PubMed, Web of Science, OVID Medline, "Cochrane Central Register of Controlled Trials," Cochrane reviews and Embase was performed from inception to June 2023 to identify studies where IN medications were administered to patients in the prehospital setting. All randomized controlled trials, observational cohort studies, case series, and case reports were included. Papers not written in English, review articles, abstracts, and non-published data (including letters to the editor) were excluded. The methodological quality of the included studies was interpreted using the Cochrane risk of bias tool and rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. No funding was received. From 4818 studies, 39 were included (seven for midazolam, five for ketamine, twelve for fentanyl, one for diamorphine, two for glucagon, and twelve for naloxone). A total of 24,097 patients were treated with IN medications across all the studies. There were five moderate quality, four low quality, and thirty very low quality studies. The potential efficacy of IN fentanyl and ketamine was demonstrated consistently throughout the studies with less clear evidence for midazolam, morphine, glucagon, and naloxone. This review was severely limited by the study quality, with most studies demonstrating "high concerns" for bias. Prehospital IN medication administration has wide-ranging potential, particularly for administering analgesia. There are likely to be certain populations, for example, pediatrics, that will benefit the most, although conclusions are limited by the quality of evidence currently available. We encourage additional research in this area, particularly with robust prospective double-blind RCTs. [ABSTRACT FROM AUTHOR]

Additional risk minimization strategies may be required to assure a positive benefit–risk balance for some therapeutic products associated with serious adverse drug reactions/risks of use, without which these products may be otherwise unavailable to patients. The goals of risk minimization strategies are often fundamentally to influence the behavior of healthcare professionals (HCPs) and/or patients and can include appropriate patient selection, provision of education and counselling, appropriate medication use, adverse drug reaction monitoring, and adoption of other elements to assure safe use, such as pregnancy prevention. Current approaches to additional risk minimization strategy development rely heavily on information provision, without full consideration of the contextual factors and multi-level influences on patient and HCP behaviors that impact adoption and long-term adherence to these interventions. Application of evidence-based behavioral science methods are urgently needed to improve the quality and effectiveness of these strategies. Evidence from the fields of adherence, health promotion, and drug utilization research underscores the value and necessity for using established behavioral science frameworks and methods if we are to achieve clinical safety goals for patients. The current paper aims to enhance additional risk minimization strategy development and effectiveness by considering how a behavioral science approach can be applied, drawing from evidence in understanding of engagement with pharmaceutical medicines as well as wider public health interventions for patients and HCPs. [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]

Chronic Myelogenous Leukaemia (CML) is a haematopoietic stem cells disease with complex dynamical behaviour. One of the effective factors in treating patients is to determine the appropriate drug dosage. A physician should test the different drug dosages through trial and error in order to find its optimal value. This procedure is normally a time‐consuming and error‐prone task that can even be harmful. The contribution of this paper is to design an intelligent control strategy, which can be used to help physicians, by finding a drug treatment regimen to minimize the number of cancer cells for a CML patient. In this paper, the eligibility traces algorithm and Q‐learning approach are adopted as sub‐optimal methods for progressively reducing the population of cancer cells. In addition, the injected dosage of the drug has improved, compared with previous methods. More importantly, the proposed method is followed by the reduction in side effects of the drug. The advantage of the backward view and the previous states investigation are applied in the Eligibility Traces algorithm. These effects increase the learning procedure and decrease the growth rate of cancer cells and total dosage of the injected drug during the treatment period of time. The proposed strategy mitigates the side effects of the drug on the normal cells. [ABSTRACT FROM AUTHOR]

Background: In a bid to end the ongoing coronavirus disease 2019 pandemic, many countries, including the UK, have rolled out mass immunisation programmes. While considered generally safe and effective, vaccines against coronavirus disease 2019 have been reported to be associated with rare and potentially adverse reactions and side effects. Case report: This paper reports an unusual case of a patient who developed a unilateral vocal fold paralysis shortly after receiving the first dose of the Oxford-AstraZeneca ChAdOx1 nCov-19 vaccine. Conclusion: To our knowledge, this is the first reported case of vocal fold paralysis following administration of the Oxford-AstraZeneca vaccine. The authors support the position that currently approved coronavirus disease 2019 vaccines remain safe and effective; however, further surveillance and vigilance using real-world data are highly encouraged. [ABSTRACT FROM AUTHOR]

Drug-Induced liver injury (DILI) is a common harmful drug reaction of some medication which can cause the damage to liver cells, or might be a chance of death. In the western countries DILI is the main cause for acute liver failure. These reactions are very common because almost all drug regimens can cause injury to liver. Most of DILI cases are harmless and they get better after stopping the offending drug. These reactions are mainly due to some pharmacological remedies, traditional medications, herbal and nutritional supplements. Due to these harmful reactions, elevation is noticed in the liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate, total bilirubin) 2N from its normal value. Drug-induced liver injury includes 1,000 of pharmacological remedies or more. Here, we review the maximum current literature, so the treatment includes timely diagnosis and removal of the doubtable medication is the key. This paper explains the different causes, pharmacological medications responsible for drug-induced liver injury, effect of covid-19 on liver injury and future perspective. It is important to be aware of and remove the suspected agent as soon as possible. There are no specific risk factors for DILI, but existing liver disease and genetic factors may be a priority for some people. Treatment of liver damage caused by drugs and herbs includes immediate drug withdrawal and supportive care aimed at alleviating unwanted symptoms. Main purpose of this paper is to deliver the info about the DILI, which are dose related, identification and consideration of disease. [ABSTRACT FROM AUTHOR]

Copyright of Animal Technology & Welfare is the property of Institute of Animal Technology of Great Britain 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.)

This paper mainly describes a platform to achieve targeted drug delivery in the next-generation wireless capsule endoscopy. Targeted drug delivery helps in giving the medicine to the affected area only instead of giving it to the entire body. The major mechanism of the proposed system is the micro-positioning of the targeted medication with a level of 1 ml. This micro-positioning enables us to place the capsule in the required direction. The proposed micro-positioning mechanism allows a needle to be positioned within a 22.5° segment of a cylindrical capsule and be extendible up to 1.5mm outside the capsule body. The locomotion of the microrobot is achieved by magnetic mechanisms, which helps in holding the capsule as well as resist the peristaltic movement when necessary. The proposed infrastructure of the 3 mechanism can be done using the combination of a single micro-motor with a volume of 200 mm. An in-intensity evaluation of the mechanics is furnished and a top-level view of the requirements important to comprehend fashionable system integration is cited right here. This paper mainly aims to give the medication to the specified location. This will reduce the reaction of the drugs especially those drugs which are used for cancer treatment. Cancer treating drug when given through blood will reach all other organs before reaching the diseased tissue or part of the organ. Not only that, but it also helps to turn down the cost of drugs used for the cure. It is envisaged that the targeted drug delivery platform will empower a new breed of capsule microrobots for therapy in addition to diagnostics for pathologies such as ulcerative colitis and small intestinal Crohn's disease. [ABSTRACT FROM AUTHOR]

Discrete choice experiments (DCEs) are a way to assess priority-setting in health care provision. This approach allows for the evaluation of individuals’ preferences as a means of adding criteria to traditional quality-adjusted life year analysis. The aim of this systematic literature review was to identify attributes for designing a DCE in order to then develop and validate a framework that supports decision-making on health technologies. Our systematic literature review replicated the methods and search terms used by de Bekker-Grob et al. 2012 and Clark et al. 2014. The Medline database was searched for articles dated between 2008 and 2015. The search was limited to studies in English that reflected general preferences and were choice-based, published as full-text articles and related to health technologies. This study included 72 papers, 52% of which focused on DCEs on drug treatments. The average number of attributes used in all included DCE studies was 5.74 (SD 1.98). The most frequently used attributes in these DCEs were improvements in health (78%), side effects (57%) and cost of treatment (53%). Other, less frequently used attributes included waiting time for treatment or duration of treatment (25%), severity of disease (7%) and value for money (4%). The attributes identified might inform future DCE surveys designed to study societal preferences regarding health technologies in order to better inform decisions in health technology assessment. [ABSTRACT FROM AUTHOR]

Objectives: We carried out a systematic review of the literature to evaluate the effect of centchroman on mastalgia as well as any side effects.Methods: The databases of the Cochrane Library, Medline (PubMed), Embase, ProQuest and ClinicalTrials.gov were systematically searched. The quality of randomised controlled clinical trials (RCTs) was assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomised clinical trials. The quality of non-randomised clinical trials was assessed using the Cochrane risk of bias assessment tool for non-randomised studies of interventions (ROBINS-I). Owing to different outcomes reporting, a meta-analysis of the results was not possible.Results: Thirteen papers were included in the study. Of these, 12 showed a significant effect of centchroman in reducing breast pain at 3 months. One study that compared the effect of centchroman with that of tamoxifen reported a significant reduction in breast pain in both groups at 3 months; the difference between the two groups was not significant. Six studies showed the effectiveness of centchroman at 6 months. None of the papers reported any serious side effects of centchroman.Conclusions: Since a meta-analysis could not be conducted and the quality of the papers was low, there was insufficient evidence to evaluate the effect of centchroman on mastalgia. It is therefore recommended to conduct well-designed RCTs to compare the effect of centchroman on mastalgia with that of a placebo or other medication. [ABSTRACT FROM AUTHOR]

Pharmacovigilance, the scientific discipline pertaining to drug safety, has been studied extensively and is progressing continuously. In this field, medical informatics techniques and interpretation play important roles, and appropriate approaches are required. In this study, we investigated and analyzed the trends of pharmacovigilance systems, especially the data collection, detection, assessment, and monitoring processes. We used PubMed to collect papers on pharmacovigilance published over the past 10 years, and analyzed a total of 40 significant papers to determine the characteristics of the databases and data analysis methods used to identify drug safety indicators. Through systematic reviews, we identified the difficulty of standardizing data and terminology and establishing an adverse drug reactions (ADR) evaluation system in pharmacovigilance, and their corresponding implications. We found that appropriate methods and guidelines for active pharmacovigilance using medical big data are still required and should continue to be developed. [ABSTRACT FROM AUTHOR]

Prediction of Adverse Drug Reactions (ADRs) has been an important aspect of Pharmacovigilance because of its impact in the pharma industry. The standard process of introduction of a new drug into a market involves a lot of clinical trials and tests. This is a tedious and time consuming process and also involves a lot of monetary resources. The faster approval of a drug helps the patients who are in need of the drug. The in silico prediction of Adverse Drug Reactions can help speed up the aforementioned process. The challenges involved are lack of negative data present and predicting ADR from just the chemical structure. Although many models are already available to predict ADR, most of the models use biological activities identifiers, chemical and physical properties in addition to chemical structures of the drugs. But for most of the new drugs to be tested, only chemical structures will be available. The performance of the existing models predicting ADR only using chemical structures is not efficient. Therefore, an efficient prediction of ADRs from just the chemical structure has been proposed in this paper. The proposed method involves a separate model for each ADR, making it a binary classification problem. This paper presents a novel CNN model called Drug Convolutional Neural Network (DCNN) to predict ADRs using chemical structures of the drugs. The performance is measured using the metrics such as Accuracy, Recall, Precision, Specificity, F1 score, AUROC and MCC. The results obtained by the proposed DCNN model outperform the competing models on the SIDER4.1 database in terms of all the metrics. A case study has been performed on a COVID-19 recommended drugs, where the proposed model predicted the ADRs that are well aligned with the observations made by medical professionals using conventional methods. [ABSTRACT FROM AUTHOR]

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: Hospital readmissions due to medication-related problems occur frequently, burdening patients and caregivers emotionally and straining health care systems economically. In times of limited health care resources, interventions to mitigate the risk of medication-related readmissions should be prioritized to patients most likely to benefit. Focusing on general internal medicine patients, this scoping review aims to identify risk factors associated with drug-related 30-day hospital readmissions. Methods: We began by searching the Medline, Embase, and CINAHL databases from their inception dates to May 17, 2022 for studies reporting risk factors for 30-day drug-related readmissions. We included all peer-reviewed studies, while excluding literature reviews, conference abstracts, proceeding papers, editorials, and expert opinions. We also conducted backward citation searches of the included articles. Within the final sample, we analyzed the types and frequencies of risk factors mentioned. Results: After deduplication of the initial search results, 1159 titles and abstracts were screened for full-text adjudication. We read 101 full articles, of which we included 37. Thirteen more were collected via backward citation searches, resulting in a final sample of 50 articles. We identified five risk factor categories: (1) patient characteristics, (2) medication groups, (3) medication therapy problems, (4) adverse drug reactions, and (5) readmission diagnoses. The most commonly mentioned risk factors were polypharmacy, prescribing problems—especially underprescribing and suboptimal drug selection—and adherence issues. Medication groups associated with the highest risk of 30-day readmissions (mostly following adverse drug reactions) were antithrombotic agents, insulin, opioid analgesics, and diuretics. Preventable medication-related readmissions most often reflected prescribing problems and/or adherence issues. Conclusions: This study's findings will help care teams prioritize patients for interventions to reduce medication-related hospital readmissions, which should increase patient safety. Further research is needed to analyze surrogate social parameters for the most common drug-related factors and their predictive value regarding medication-related readmissions. [ABSTRACT FROM AUTHOR]

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]

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]