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Corticosteroids (CSs) are widely used in oncology, presenting several different indications. They are useful for induction of apoptosis in hematological neoplasms, for management of anaphylaxis and cytokine release/hypersensitivity reaction and for the symptomatic treatment of many tumour- and treatment-related complications. If the employment of CSs in the oncological setting results in several benefits for patients and satisfaction for clinicians, on the other hand, many potential adverse events (AEs), both during treatment and after withdrawal of CSs, as well as the duality of the effects of these compounds in oncology, recommend being cautious in clinical practice. To date, several gray zones remain about indications, contraindications, dose, and duration of treatment. In this article, a panel of experts provides a critical review on CSs therapy in oncology, focusing on mechanisms of action and pharmacological characteristics, current and emerging therapeutic indications/contraindications, AEs related to CSs treatment, and the impact on patient outcome. [Display omitted] • Systemic Corticosteroids (CSs) are a cornerstone in the management of cancer patients, for treatment of cancer- and anti-cancer treatment-related symptoms, for management of anaphylaxis and cytokine release/hypersensitivity reaction and oncological emergencies. • Different types of adverse events related to CSs treatment are expected and need to be prevented and minimized. • To date, some concerns remain on the effects of CSs on tumour growth and response to anti-cancer therapy. • A prudent and conscientious use of CSs should be recommended in cancer patients [ABSTRACT FROM AUTHOR]

Background: The field of digital mental health has followed an exponential growth trajectory in recent years. While the evidence base has increased significantly, its adoption within health and care services has been slowed by several challenges, including a lack of knowledge from researchers regarding how to navigate the pathway for mandatory regulatory approval. This paper details the steps that a team must take to achieve the required approvals to carry out a research study using a novel digital mental health intervention. We used a randomised controlled trial of a digital mental health intervention called STOP (Successful Treatment of Paranoia) as a worked example. Methods: The methods section explains the two main objectives that are required to achieve regulatory approval (MHRA Notification of No Objection) and the detailed steps involved within each, as carried out for the STOP trial. First, the existing safety of digital mental health interventions must be demonstrated. This can refer to literature reviews, any feasibility/pilot safety data, and requires a risk management plan. Second, a detailed plan to further evaluate the safety of the digital mental health intervention is needed. As part of this we describe the STOP study's development of a framework for categorising adverse events and based on this framework, a tool to collect adverse event data. Results: We present literature review results, safety-related feasibility study findings and the full risk management plan for STOP, which addressed 26 possible hazards, and included the 6-point scales developed to quantify the probability and severity of typical risks involved when a psychiatric population receives a digital intervention without the direct support of a therapist. We also present an Adverse Event Category Framework for Digital Therapeutic Devices and the Adverse Events Checklist—which assesses 15 different categories of adverse events—that was constructed from this and used in the STOP trial. Conclusions: The example shared in this paper serves as a guide for academics and professionals working in the field of digital mental health. It provides insights into the safety assessment requirements of regulatory bodies when a clinical investigation of a digital mental health intervention is proposed. Methods, scales and tools that could easily be adapted for use in other similar research are presented, with the expectation that these will assist other researchers in the field seeking regulatory approval for digital mental health products. [ABSTRACT FROM AUTHOR]

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Conversational agents (CA) are becoming very popular to deliver digital health interventions. These dialog-based systems are interacting with patients using natural language which might lead to misunderstandings and misinterpretations. To avoid patient harm, safety of health CA has to be ensured. This paper raises awareness on safety when developing and distributing health CA. For this purpose, we identify and describe facets of safety and make recommendations for ensuring safety in health CA. We distinguish three facets of safety: 1) system safety, 2) patient safety, and 3) perceived safety. System safety comprises data security and privacy which has to be considered when selecting technologies and developing the health CA. Patient safety is related to risk monitoring and risk management, to adverse events and content accuracy. Perceived safety concerns a user's perception of the level of danger and user's level of comfort during the use. The latter can be supported when data security is guaranteed and relevant information on the system and its capabilities are provided. [ABSTRACT FROM AUTHOR]

Background: Clinicians and researchers should consider the expected benefits and potential harms of an intervention. Parenting programmes are a widely used evidence-based intervention for child behaviour problems. However, few data are available on potential negative effects. The aims of this paper were to increase systematic knowledge of adverse event (AE) assessment in parenting programmes and to provide an AE assessment tool. Methods: As part of the RISE project (prevention of child mental health problems in South-eastern Europe—adapt, optimise, test and extend parenting for lifelong health), we developed and tested an AE assessment procedure in three sequential studies for parents of children with child behaviour problems aged 2 to 9 years in North Macedonia, Republic of Moldova, and Romania. This paper reports on the development of the assessment tool in phase 1 (N = 140), phase 2 (N = 835), and the final experiences with using the optimised procedures in phase 3 (multisite randomised controlled trial, N = 823) in which AEs were assessed before, three times during intervention delivery, and at 1 year follow-up. At each time point, the participants completed a 12-item AE checklist. If moderate-to-severe problems of parent or child were reported, a structured follow-up interview was conducted. Results: The response rate on the AE assessment tool increased from 6% (phase 1) to 100% (phase 3) indicating improvement in collecting these data based on the experiences of each phase. Results of the RCT (phase 3) showed generally low (S)AE frequencies with the finally optimised procedure: During the intervention, no serious adverse events (SAE) were registered; at least one AE was reported by 10% (after the first session), 7% (after the third session), and 4% (after the last fifth session) of participants. None of the identified (S)AEs was causally related to the study or intervention. Cost–benefit considerations are needed to determine the best way to ensure participant safety in parenting programmes. Conclusion: The applied active AE assessment procedure provides a comprehensive AE assessment tool that can be used by others—with adaptations for the specific context, if needed. Based on our experiences, we outline recommendations for future studies. Trial registration: ClinicalTrials.gov, registration number phase 1: NCT03552250; phase 2: NCT03865485, phase 3: . Registered on 13 January 2021. [ABSTRACT FROM AUTHOR]

Background: The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers. Methods: Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs. Results: SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard. Conclusions: The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs. [ABSTRACT FROM AUTHOR]

Introduction: The World Health Organization (WHO) recommends vaccination against hepatitis B as soon as possible following birth for all infants, regardless of prematurity. Hepatitis B vaccination at birth is clearly justified, represents a crucial step in the global control of perinatally acquired hepatitis B and there are no safety concerns in infants born at term. However, there is limited information on the safety of the hepatitis B vaccine in preterm infants, whose immune responses and morbidity risk differ from those in infants born at term. Objectives: The objectives of this paper are to systematically review the literature regarding the safety and risk of adverse events following immunisation (AEFIs) associated with the administration of the hepatitis B vaccine (monovalent or as part of a combination vaccine) to preterm infants. Methods: We performed a search for relevant papers published between 1 January 2002 and 30 March 2023 in the Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials and CINAHL Plus databases. Two authors independently reviewed and analysed each article to include in the systematic review. Narrative synthesis is presented. Results: Twenty-one relevant papers were identified and included in this systematic review. The vast majority of data pertained to multi-antigen (combination) vaccine preparations and vaccination episodes from 6 weeks of age onwards. We found no publications investigating the timing of the birth dose of the hepatitis B vaccine, and AEFI reporting was exclusively short-term (hours to days following administration). There was substantial variability in the reported rate of AEFIs between studies, ranging from 0% to 96%. Regardless of frequency, AEFIs were mostly minor and included injection site reactions, temperature instability and self-limiting cardiorespiratory events. Six studies reported serious adverse events (SAEs) such as the requirement for escalation of respiratory support. However, these occurred predominantly in high-risk infant populations and were rare (~1%). Using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, the certainty of evidence was assessed as very low. Conclusions: Despite substantial variability between the relatively small number of published studies in terms of cohort selection, definitions, vaccine preparations and reporting, hepatitis B-containing vaccines (mostly as combination vaccines) appear to be relatively well tolerated in preterm infants from 6 weeks of age. Research focusing on the safety of hepatitis B vaccine in preterm infants specifically within 7 days of birth is lacking, particularly regarding long-term morbidity risk. Further research in this area is required. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Dexmedetomidine is commonly used in hospitals for sedation during procedurals. It has been considered safe even though studies have shown that it may cause bradycardia and hypotension. The aim of this study was to map the current evidence regarding potential risks of sedation of children with dexmedetomidine.Two database searches were conducted to gather all articles published through 30 January 2024 that matched the inclusion criteria. PubMed and Embase were chosen for the initial search. Search terms were chosen to create a broad systematic search that would include articles reporting adverse events during procedural sedation on children. From the included articles, data on type of sedation, administration, patient characteristics, endpoints and number of adverse events were collected.After the initial search, 357 individual papers were screened and 41 papers were included. The most common adverse event reported was bradycardia. In almost 40% of the articles that measured oxygen saturation, one or more incidents of desaturation occurred. 27% reported that interventions to prevent further harm were preformed, most of the interventions were to improve oxygenation.There is a need for further investigation regarding adverse events, especially respiratory adverse events during sedation with dexmedetomidine. [ABSTRACT FROM AUTHOR]

Background: Epilepsy ranks among the most prevalent neurological conditions worldwide. Cannabidiol (CBD) has received authorization for epilepsy treatment, yet utilizing CBD is linked to a variety of adverse events (AEs). This umbrella review aims to explore risk and frequency of AEs in epilepsy patients undergoing treatment with CBD. Methods: International electronic databases comprising Scopus, PubMed, and Web of Science were extensively searched from the most ancient data accessible until May 2024. In line with fundamental principle of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA), this umbrella review was executed. RStudio software version 2023.03.1 along with R software 4.3.2 was used for our statistical analyses. Results: Thirteen meta-analyses and systematic reviews were included. CBD use in epileptic patients compared to controls can be meaningfully linked with 10.87% becoming seizure-free (RD: 10.87%, 95%CI: 2.39%, 19.34%; I2 = 80%). Compared to controls, a meaningful 73% increase in 50% or greater reduction in seizure frequency was observed (RR: 1.73, 95%CI: 1.47, 2.03; I2 = 0%). In epileptic individuals who using CBD with the dosage of 20 mg/kg/d, a higher incidence of treatment withdrawal was detected (RR: 4.39, 95%CI: 2.46, 7.83; I2 = 0%). Conclusion: In this umbrella review of meta-analyses and systematic reviews, CBD use in epileptic patients was linked to an increased risk of ample AEs. Further research, specifically targeting various epilepsy categories, is essential to fully understand the effectiveness and potential side effects of CBD across different epilepsy forms. [ABSTRACT FROM AUTHOR]

Continuous vital sign monitoring (CVSM) with wireless sensors in general hospital wards can enhance patient care. An artificial intelligence (AI) layer is crucial to allow sensor data to be managed by clinical staff without over alerting from the sensors. With the aim of summarizing peer-reviewed evidence for AI support in CVSM sensors, we searched PubMed and Embase for studies on adult patients monitored with CVSM sensors in general wards. Peer-reviewed evidence and white papers on the official websites of CVSM solutions were also included. AI classification was based on standard definitions of simple AI, as systems with no memory or learning capabilities, and advanced AI, as systems with the ability to learn from past data to make decisions. Only studies evaluating CVSM algorithms for improving or predicting clinical outcomes (e.g., adverse events, intensive care unit admission, mortality) or optimizing alarm thresholds were included. We assessed the promised level of AI for each CVSM solution based on statements from the official product websites. In total, 467 studies were assessed; 113 were retrieved for full-text review, and 26 studies on four different CVSM solutions were included. Advanced AI levels were indicated on the websites of all four CVSM solutions. Five studies assessed algorithms with potential for applications as advanced AI algorithms in two of the CVSM solutions (50%), while 21 studies assessed algorithms with potential as simple AI in all four CVSM solutions (100%). Evidence on algorithms for advanced AI in CVSM is limited, revealing a discrepancy between promised AI levels and current algorithm capabilities. [ABSTRACT FROM AUTHOR]

Background: Despite Africa's significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed. Methods: As a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings. Outcome. Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up. Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants. Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms. Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities. Conclusion: Conducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings. [ABSTRACT FROM AUTHOR]

Adverse events suffer from poor reporting within randomised controlled trials, despite them being crucial to the evaluation of a treatment. A recent update to the CONSORT harms checklist aims to improve reporting by providing structure and consistency to the information presented. We propose an extension wherein harms would be reported in conjunction with effectiveness outcome(s) rather than in silo to provide a more complete picture of the evidence acquired within a trial. Benefit-risk methods are designed to simultaneously consider both benefits and risks, and therefore, we believe these methods could be implemented to improve the prominence of adverse events when reporting trials. The aim of this article is to use case studies to demonstrate the practical utility of benefit-risk methods to present adverse events results alongside effectiveness results. Two randomised controlled trials have been selected as case studies, the Option-DM trial and the SANAD II trial. Using a previous review, a shortlist of 17 benefit-risk methods which could potentially be used for reporting RCTs was created. From this shortlist, three benefit-risk methods are applied across the two case studies. We selected these methods for their usefulness to achieve the aim of this paper and which are commonly used in the literature. The methods selected were the Benefit-Risk Action Team (BRAT) Framework, net clinical benefit (NCB), and the Outcome Measures in Rheumatology (OMERACT) 3 × 3 table. Results using the benefit-risk method added further context and detail to the clinical summaries made from the trials. In the case of the SANAD II trial, the clinicians concluded that despite the primary outcome being improved by the treatment, the increase in adverse events negated the improvement and the treatment was therefore not recommended. The benefit-risk methods applied to this case study outlined the data that this decision was based on in a clear and transparent way. Using benefit-risk methods to report the results of trials can increase the prominence of adverse event results by presenting them alongside the primary efficacy/effectiveness outcomes. This ensures that all the factors which would be used to determine whether a treatment would be recommended are transparent to the reader. [ABSTRACT FROM AUTHOR]

This paper presents a scoping review of the peer-reviewed literature regarding reported risks, adverse effects and mitigation factors related to providing mental health services using telehealth. The paper aims to describe risks and risk management strategies. Publications were included if they reported upon risks, adverse events or mitigation factors experienced, hypothesised or discussed for: any population (any country, any age), service (any mental health services), intervention (telehealth), English language, 2010 to 10 July 2021, any publication type (commentary, research, policy), excluding protocol papers, and self-help tools. The following databases were searched: PsycINFO (from 2010 to 10 July 2021), MEDLINE (2010 to 10 July 2021) and the Cochrane Database from 2010 to 10 July 2021. The search strategy resulted in 1,497 papers and after exclusions a final 55 articles were selected. Results of this scoping review are presented in terms of types of risk, risk by client population, risk by modality (eg group therapy using telehealth) and risk management. Recommendations for future research include gathering and publishing more detailed information regarding near-miss and actual adverse events when delivering mental health assessment and care using telehealth. In clinical practice, training is required for potential adverse events, and to prevent them and reporting mechanisms in place to collate and learn from these. [ABSTRACT FROM AUTHOR]

The objective of this paper is to conduct a systematic thematic review of adverse events, safety, and toxicity of traditional ayahuasca plant preparations and its main psychoactive alkaloids (dimethyltryptamine [DMT], harmine, harmaline, and tetrahydroharmine), including discussing clinical considerations (within clinical trials or approved settings). A systematic literature search of preclinical, clinical, epidemiological, and pharmacovigilance data (as well as pertinent reviews and case studies) was conducted for articles using the electronic databases of PubMed and Web of Science (to 6 July 2023) and PsycINFO, ClinicalTrials.gov, and Embase (to 21 September 2022) and included articles in English in peer-reviewed journals. Additionally, reference lists were searched. Due to the breadth of the area covered, we presented the relevant data in a thematic format. Our searches revealed 78 relevant articles. Data showed that ayahuasca or DMT is generally safe; however, some adverse human events have been reported. Animal models using higher doses of ayahuasca have shown abortifacient and teratogenic effects. Isolated harmala alkaloid studies have also revealed evidence of potential toxicity at higher doses, which may increase with co-administration with certain medications. Harmaline revealed the most issues in preclinical models. Nevertheless, animal models involving higher-dose synthetic isolates may not necessarily be able to be extrapolated to human use of therapeutic doses of plant-based extracts. Serious adverse effects are rarely reported within healthy populations, indicating an acceptable safety profile for the traditional use of ayahuasca and DMT in controlled settings. Further randomized, controlled trials with judicious blinding, larger samples, and longer duration are needed. [ABSTRACT FROM AUTHOR]

In the postmarket drug and vaccine safety surveillance, when the number of adverse events follows a Poisson distribution, the ratio between the exposed and the unexposed person‐time information is the random variable that governs the decision rule about the safety of the drug or vaccine. The probability distribution function of such a ratio is derived in this paper. Exact point and interval estimators for the relative risk are discussed as well as statistical hypothesis testing. To the best of our knowledge, this is the first paper that provides an unbiased estimator for the relative risk based on the person‐time ratio. The applicability of this new distribution is illustrated through a real data analysis aimed to detect increased risk of occurrence of Myocarditis/Pericarditis following mRNA COVID‐19 vaccination in Manitoba, Canada. [ABSTRACT FROM AUTHOR]

The application of digital interventions in healthcare beyond research has been translated in the development of software as a medical device. Along with corresponding regulations for medical devices, there is a need for assessing adverse events to conduct post-market surveillance and to appropriately label digital health interventions to ensure proper use and patient safety. To date unexpected consequences of digital health interventions are neglected or ignored, or at least remain undescribed in literature. This paper is intended to raise awareness across the research community about these upcoming challenges. We recommend that - together with developing a new research field of digitalovigilance - a systematic assessment and monitoring of adverse events and unexpected interactions be included in clinical trials, along with the reporting of such events and the conduct of meta-analyses on critical aspects. [ABSTRACT FROM AUTHOR]

Issues: Established literature suggests that electronic cigarettes (EC) are more effective than traditional nicotine replacement therapies (NRT) as a smoking cessation aid, but the factors that mediate this difference remain poorly understood. We examine how adverse events (AE) associated with EC use relative to NRTs differ, with the view that differences in AEs experienced may drive differences in use and compliance. Approach: Papers for inclusion were identified via a three‐tiered search strategy. Eligible articles involved healthy participants and compared nicotine ECs to non‐nicotine ECs or NRTs and reported frequency of AE as an outcome. Random‐effects meta‐analyses were conducted to compare the likelihood for each of the AEs between nicotine ECs, non‐nicotine placebo ECs and NRTs. Key Findings: A total of 3756 papers were identified, of which 18 were meta‐analysed (10 cross‐sectional and 8 randomised controlled trials). Meta‐analytic results found no significant difference in the rates of reported AEs (i.e., cough, oral irritation, nausea) between nicotine ECs and NRTs, and between nicotine and non‐nicotine placebo ECs. Implications: The variation in the incidence of AEs likely does not explain user preferences of ECs to NRTs. Incidence of common AEs reported because of EC and NRT use did not differ significantly. Future work will need to quantify both the adverse and favourable effects of ECs to understand the experiential mechanisms that drive the high uptake of nicotine ECs relative to established NRTs. Conclusions: There is inconclusive evidence on the incidence of AEs experience when using ECs compared to NRTs, possibly given the small sample size of studies. [ABSTRACT FROM AUTHOR]

Aim: To identify outcomes of missed nursing care for adult patients. Design: A five‐stage rapid review process was conducted as follows: refining the question, retrieving relevant studies, determining the studies to be included, organizing the data and synthesizing the results. Methods: Papers published between 2010–2020 that focused on the UK, Europe, the USA and Oceania were searched for keywords in the title and abstract in major databases. The articles that identified the impact of missed nursing care on adults in health care were selected. Results: Seventeen articles met the criteria. Major impacts of missed care in adult settings were increases in mortality, adverse events and failure to maintain. These same studies also identified a range of causative factors linked to ward environment, inadequate staffing levels and skills mix although are inconclusive. Solutions include continuing education, ward and work re‐design, and appropriate skill level. [ABSTRACT FROM AUTHOR]

In this paper, we discuss challenges associated with implementing a policy for Ancillary Care (AC) for related and unrelated (serious) adverse events during an Ebola vaccine trial conducted in a remote area of the Democratic Republic of the Congo. Conducting clinical trials in resourceconstrained settings can raise context-related challenges that have implications for study participants' health and wellbeing. During the Ebola vaccine study, three participants were injured in road traffic accidents, but there were unexpected difficulties when trying to apply the AC policy. First, because of the nature of the adverse events, the insurer refused to cover the costs. Second, the AC policy did not address treatments by traditional medicine, even though traditional medicines are frequently used and highly trusted in the study community. This highlighted a contrast between the researchers' well-intentioned AC approach and the participants' legitimate preferences. The way in which researchers should address their responsibility to provide AC is not straightforward; it requires contextualization. Our experience highlights the importance of involving community representatives and the local ethics committee to ensure development of an AC policy that is culturally and ethically appropriate. Additionally, the insurance contract should clearly stipulate which adverse events are linked to the trial participation, and thus eligible for coverage, to avoid controversies when claims are made. [ABSTRACT FROM AUTHOR]

Following the results of the CROWN phase III trial, the third-generation macrocyclic ALK inhibitor lorlatinib has been introduced as a salvage option after the failure of a first-line TKI in ALK-rearranged NSCLC, while its precise role in the therapeutic algorithm of ROS1 positive disease is still to be completely defined. The ability to overcome acquired resistance to prior generation TKIs (alectinib, brigatinib, ceritinib, and crizotinib) and the high intracranial activity in brain metastatic disease thanks to increased blood–brain barrier penetration are the reasons for the growing popularity and interest in this molecule. Nevertheless, the major vulnerability of this drug resides in a peculiar profile of related collateral events, with neurological impairment being the most conflicting and debated clinical issue. The cognitive safety concern, the susceptibility to heterogeneous resistance pathways, and the absence of a valid alternative in the second line are strongly jeopardizing a potential paradigm shift in this oncogene-addicted disease. So, when prescribing lorlatinib, clinicians must face two diametrically opposed characteristics: a great therapeutic potential without the intrinsic limitations of its precursor TKIs, a cytotoxic activity threatened by suboptimal tolerability, and the unavoidable onset of resistance mechanisms we cannot properly manage yet. In this paper, we give a critical point of view on the stepwise introduction of this promising drug into clinical practice, starting from its innovative molecular and biochemical properties to intriguing future developments, without forgetting its weaknesses. [ABSTRACT FROM AUTHOR]

There is a very wide spectrum of epilepsies and developmental and epileptic encephalopathies that affect children, from self-limited forms, not necessarily requiring treatment, to severe drug-resistant ones. In this perspective, the authors discuss the main factors to consider before drug prescription in children, considering the most recent clinical research, including age, seizure type, epilepsy syndrome, etiology, efficacy and safety profile, comorbidities, gender, available formulations, costs and drug coverage, and regulatory issues. The literature search was conducted through a PubMed search on antiseizure medications for patients aged 0–18, with respect to each of the aforementioned factors, and by checking the reference lists of relevant papers. The most expanding field of research and innovation for clinical practice is precision medicine, which addresses the holistic treatment of genetic epilepsies and developmental and epileptic encephalopathies. It achieves this by addressing their detrimental effects on synapses, neurotransmission, and cellular signaling pathways with the double aim to treat seizures and to rescue neurodevelopmental trajectories, but also the issue of adverse events and drug resistance through pharmacogenomics. [ABSTRACT FROM AUTHOR]

Background: The risk of suicide for agricultural workers in parts of the United Kingdom (UK) is almost twice the national average. Existing literature has suggested that adverse farming events, where failure is determined by uncontrollable and unpredictable forces, may be to blame. Yet, the impact of such events on farmer suicidality has not been explicitly explored. Aims: The present paper therefore aimed to investigate the relationship between adverse farming events and suicidal ideation in farmers. Methods: A cross-sectional questionnaire battery was disseminated between July 2018 and February 2019, and completed by 170 adult farmers. Results: Over a 12-month period, 88.8% reported that they had experienced an adverse farming event and 32.9% said that they had experienced suicidal thoughts. Correlational analysis revealed a relationship between these variables. Conclusions: The high prevalence of suicidal ideation within farmers demonstrates a critical need for intervention. Likewise, the prevalence of adverse farming events suggests that interventions need to be appropriately tailored, with greater understanding about the impact of such events on the mental wellbeing of farmers. [ABSTRACT FROM AUTHOR]

Abstract Background The field of digital mental health has followed an exponential growth trajectory in recent years. While the evidence base has increased significantly, its adoption within health and care services has been slowed by several challenges, including a lack of knowledge from researchers regarding how to navigate the pathway for mandatory regulatory approval. This paper details the steps that a team must take to achieve the required approvals to carry out a research study using a novel digital mental health intervention. We used a randomised controlled trial of a digital mental health intervention called STOP (Successful Treatment of Paranoia) as a worked example. Methods The methods section explains the two main objectives that are required to achieve regulatory approval (MHRA Notification of No Objection) and the detailed steps involved within each, as carried out for the STOP trial. First, the existing safety of digital mental health interventions must be demonstrated. This can refer to literature reviews, any feasibility/pilot safety data, and requires a risk management plan. Second, a detailed plan to further evaluate the safety of the digital mental health intervention is needed. As part of this we describe the STOP study’s development of a framework for categorising adverse events and based on this framework, a tool to collect adverse event data. Results We present literature review results, safety-related feasibility study findings and the full risk management plan for STOP, which addressed 26 possible hazards, and included the 6-point scales developed to quantify the probability and severity of typical risks involved when a psychiatric population receives a digital intervention without the direct support of a therapist. We also present an Adverse Event Category Framework for Digital Therapeutic Devices and the Adverse Events Checklist—which assesses 15 different categories of adverse events—that was constructed from this and used in the STOP trial. Conclusions The example shared in this paper serves as a guide for academics and professionals working in the field of digital mental health. It provides insights into the safety assessment requirements of regulatory bodies when a clinical investigation of a digital mental health intervention is proposed. Methods, scales and tools that could easily be adapted for use in other similar research are presented, with the expectation that these will assist other researchers in the field seeking regulatory approval for digital mental health products.

Pancreatic stones are the result of pathophysiologic changes in chronic pancreatitis with an incidence of more than 90%. At present, pancreatic extracorporeal shock wave lithotripsy (P-ESWL) can be used as the first-line treatment for large or complex stones. Although a large number of studies have proven the safety and effectiveness of P-ESWL, we should also pay attention to postoperative adverse events, mainly due to the scattering of shock waves in the conduction pathway. Adverse events can be classified as either complications or transient adverse events according to the severity. Because the anatomic location of organs along the shock wave conducting pathway differs greatly, adverse events after P-ESWL are varied and difficult to predict. This paper outlines the mechanism, definition, classification, management and risk factors for adverse events related to P-ESWL. It also discusses the technique of P-ESWL, indications and contraindications of P-ESWL, and adverse events in special populations. [ABSTRACT FROM AUTHOR]

Sedation is common during digestive endoscopy to provide comfort and pain relief for patients. However, the use of sedation in endoscopy also poses potential risks, and recent issues have been raised regarding its safety and administration. This literature review paper will discuss the most recent developments in the field of sedation in digestive endoscopy, including the adverse events that might be associated with sedation and how to manage it, the legal issues associated with administration, the impact of COVID-19 on sedation practices, and sedation in special situations. It will also touch upon the current guidelines and recommendations for sedation, including the importance of patient selection and monitoring and the need for training and certification for endoscopists administering sedation. The review will also analyse studies evaluating the safety and efficacy of various sedation techniques, including propofol, midazolam, and others. It will examine the benefits and drawbacks of these agents. [ABSTRACT FROM AUTHOR]

Purpose: Although medicinal cannabis is prescribed for conditions such as pain, epilepsy, nausea and vomiting during cancer treatment, evidence about associated adverse side effects is still evolving. Because adverse events (AEs) might impact the performance of workers, it is important to consider their implications on workplace health and safety (WHS). This study aimed to map the types and prevalence of the AEs associated with medical cannabis and articulate how those events could impact WHS. Methods: A scoping review of systematic reviews and/or meta-analyses published between 2015 and March 2021 was performed to identify the AEs of medicinal cannabis in adults. Publications in English and full text available online were collected from Embase, MEDLINE, PsychINFO, PubMed, Scopus, and Web of Science. Results: Of 1,326 papers identified from the initial search, 31 met the inclusion criteria and were analyzed. The studies reported various AEs with the most predominant being sedation, nausea/vomiting, dizziness, and euphoria. Acute and chronic pain was the most prevalent disorder under review. Conclusions: Adverse events associated with the use of medicinal cannabis could increase workplace risks, including decreased alertness and reaction times, increased absenteeism, reduced ability to safely drive or operate machinery and an increased probability of falling. Focused research into the risk to workers and workplaces from the use of medical cannabis and related human performance impairment is urgently warranted. [ABSTRACT FROM AUTHOR]

Annotations enrich text corpora and provide necessary labels for natural language processing studies. To reason and infer underlying implicit knowledge captured by labels, an ontology is needed to provide a semantically annotated corpus with structured domain knowledge. Utilizing a corpus of adverse event documents annotated for sepsis-related signs and symptoms as a use case, this paper details how a terminology and corresponding ontology were developed. The Annotated Adverse Event NOte TErminology (AAENOTE) represents annotated documents and assists annotators in annotating text. In contrast, the complementary Catheter Infection Indications Ontology (CIIO) is intended for clinician use and captures domain knowledge needed to reason and infer implicit information from data. The approach taken makes ontology development understandable and accessible to domain experts without formal ontology training. [ABSTRACT FROM AUTHOR]

Dermal filler and botulinum toxin injections are among the most performed non-invasive procedures for rejuvenation and contouring, internationally. Although most dermal fillers and approved botulinum toxins are well tolerated with a high safety profile, adverse events and/or complications can happen. Injection-related sequelae and side effects are usually rare, mild, transient, and self-limiting in nature. However, devastating and life-changing complications, such as intravascular occlusion, skin necrosis, permanent visual impairment, and stroke, have been reported. Risk reduction measures include an in-depth knowledge of anatomy, physiology, and pharmacology, correct patient selection, correct identification of clinical indications, and, fundamentally, the importance of appropriate skill and training. In this paper, some of the complications are discussed and advice on how to minimise adverse events and complications from these injectables is provided. [ABSTRACT FROM AUTHOR]

Abstract Background Clinicians and researchers should consider the expected benefits and potential harms of an intervention. Parenting programmes are a widely used evidence-based intervention for child behaviour problems. However, few data are available on potential negative effects. The aims of this paper were to increase systematic knowledge of adverse event (AE) assessment in parenting programmes and to provide an AE assessment tool. Methods As part of the RISE project (prevention of child mental health problems in South-eastern Europe—adapt, optimise, test and extend parenting for lifelong health), we developed and tested an AE assessment procedure in three sequential studies for parents of children with child behaviour problems aged 2 to 9 years in North Macedonia, Republic of Moldova, and Romania. This paper reports on the development of the assessment tool in phase 1 (N = 140), phase 2 (N = 835), and the final experiences with using the optimised procedures in phase 3 (multisite randomised controlled trial, N = 823) in which AEs were assessed before, three times during intervention delivery, and at 1 year follow-up. At each time point, the participants completed a 12-item AE checklist. If moderate-to-severe problems of parent or child were reported, a structured follow-up interview was conducted. Results The response rate on the AE assessment tool increased from 6% (phase 1) to 100% (phase 3) indicating improvement in collecting these data based on the experiences of each phase. Results of the RCT (phase 3) showed generally low (S)AE frequencies with the finally optimised procedure: During the intervention, no serious adverse events (SAE) were registered; at least one AE was reported by 10% (after the first session), 7% (after the third session), and 4% (after the last fifth session) of participants. None of the identified (S)AEs was causally related to the study or intervention. Cost–benefit considerations are needed to determine the best way to ensure participant safety in parenting programmes. Conclusion The applied active AE assessment procedure provides a comprehensive AE assessment tool that can be used by others—with adaptations for the specific context, if needed. Based on our experiences, we outline recommendations for future studies. Trial registration ClinicalTrials.gov, registration number phase 1: NCT03552250; phase 2: NCT03865485, phase 3: NCT04721730 . Registered on 13 January 2021.

The long-term use of psychopharmacology medications in autism spectrum disorder (ASD) hitherto remains controversial due to a lack of evidence about safety and tolerability. In this regard, genotyping the metabolizing enzyme cytochrome P450 (CYP) 2D6, especially its extreme phenotypes, could help to prevent drug-related adverse reactions or adverse events (AEs). There are several medications warranting CYP2D6 screening that are consumed by people with ASD, such as risperidone and aripiprazole to name a few. A naturalistic observational study was carried out in participants with ASD to analyze the influence of the CYP2D6 phenotype in drug tolerability using a local pharmacovigilance system created for this study. In this case, AEs were identified from participants' electronic health records (EHRs) and paper registries. Other variables were collected: socio-demographic information, comorbidities, and psychopharmacology prescriptions (polypharmacy defined as ≥4 simultaneous prescriptions) and doses. The genetic analysis included allelic discrimination (CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, and *41) and copy number variations. All of these were used to determine theoretical phenotypes of the metabolic profiles: poor (PM); intermediate (IM); normal (NM); and ultra-rapid (UM). Sex differences were analyzed. A total of 71 participants (30 ± 10 years old, 82% male, 45% CYP2D6 NM phenotype (32 participants)) with a median of 3 (IQR 2–4) comorbidities per person, mainly urinary incontinence (32%) and constipation (22%), were included. CYP2D6 UM showed the highest rate of polypharmacy, whilst, IM participants had the highest rates of neurological and psychiatric AEs, even worse if a CYP2D6 inhibitor drug was prescribed simultaneously. CYP2D6 pharmacogenomics and the monitoring of new antipsychotic prescriptions may make a difference in medication safety in adults with ASD. Particularly in those with psychopharmacology polymedication, it can help with AE avoidance and understanding. [ABSTRACT FROM AUTHOR]

In recent years, the U.S. Food and Drug Administration (FDA) has seen an increase in microfluidic medical device submissions, likely stemming from recent advancements in microfluidic technologies. This recent trend has only been enhanced during the COVID-19 pandemic, as microfluidic-based test kits have been used for diagnosis. To better understand the implications of this emerging technology, device submissions to the FDA from 2015 to 2021 containing microfluidic technologies have been systematically reviewed to identify trends in microfluidic medical applications, performance tests, standards used, fabrication techniques, materials, and flow systems. More than 80% of devices with microfluidic platforms were found to be diagnostic in nature, with lateral flow systems accounting for about 35% of all identified microfluidic devices. A targeted analysis of over 40,000 adverse event reports linked to microfluidic technologies revealed that flow, operation, and data output related failures are the most common failure modes for these device types. Lastly, this paper highlights key considerations for developing new protocols for various microfluidic applications that use certain analytes (e.g., blood, urine, nasal-pharyngeal swab), materials, flow, and detection mechanisms. We anticipate that these considerations would help facilitate innovation in microfluidic-based medical devices. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are widely used in the treatment of lung cancer, especially in the first-line treatment of advanced NSCLC, and EGFR-TKIs monotherapy has achieved better efficacy and tolerability compared with standard chemotherapy. However, acquired resistance to EGFR-TKIs and associated adverse events pose a significant obstacle to targeted lung cancer therapy. Therefore, there is an urgent need to seek effective interventions to overcome these limitations. Natural medicines have shown potential therapeutic advantages in reversing acquired resistance to EGFRTKIs and reducing adverse events, bringing new options and directions for EGFRTKIs combination therapy. In this paper, we systematically demonstrated the resistance mechanism of EGFR-TKIs, the clinical strategy of each generation of EGFR-TKIs in the synergistic treatment of NSCLC, the treatment-related adverse events of EGFR-TKIs, and the potential role of traditional Chinese medicine in overcoming the resistance and adverse reactions of EGFR-TKIs. Herbs and active compounds have the potential to act synergistically through multiple pathways and multiple mechanisms of overall regulation, combined with targeted therapy, and are expected to be an innovative model for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Severity grading systems for complications in surgical patients have been used since 1992. An increasing assessment of these instruments in pediatric surgery is also noticed, without their validation in children. To analyze the current practice, we performed a literature review with focus on the assessment and grading of complications. The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies reporting on postoperative complications as a primary or secondary endpoint using a severity grading system were included. Definition for simple adverse events, classification systems used, and the time horizon of postoperative documentation were analyzed. A total of 566 articles were screened, of which 36 met the inclusion criteria. About 86.1% of the papers were retrospective and 13.9% prospective analyses. None of the studies were prospective-randomized trials. Twenty (55.6%) studies did not include a definition of adverse events, whereas the remaining 16 (44.4%) showed variations in their definitions. All studies applied the Clavien-Dindo classification, whereas five (13.9%) additionally used the Comprehensive Complication Index. One study compared alternative grading instruments with the Clavien-Dindo classification, without demonstrating the superiority of any classification in pediatric surgery. Twenty-two studies (61.1%) did not report the time horizon of perioperative complication documentation, while 8 studies (22.2%) used 30 days and 6 studies (16.7%) used 3 months of postoperative documentation. Definition and classification of postoperative complications are inconsistent in the pediatric surgical literature. Establishment of a standardized protocol is mandatory to accurately compare outcome data. [ABSTRACT FROM AUTHOR]

Purpose: The primary objective of this study was to determine if dihydropyrimidine dehydrogenase (DPD) activity measured in peripheral blood mononuclear cells (PBMCs) is related to adverse events during fluoropyrimidine therapy. Methods: A retrospective cohort study was conducted. The study population included 481 patients who received fluoropyrimidine treatment and for whom relevant patient characteristics were known and adverse events were noted in the electronic health records. Factors besides DPD phenotype that could affect the incidence of adverse events were corrected for using log regression. These log regression models were used to identify an association between the DPD phenotype measured in PBMCs and adverse events. Results: Patients with a decreased DPD activity measured in PBMCs suffered more adverse events. Results from log regression data show that this effect remains significant after correcting for dosage, chemotherapy regimen and relevant patient characteristics. Conclusion: A significant correlation was found between reduced DPD enzyme activity in PBMCs and adverse events. The findings in this paper support further exploring DPD phenotyping as a method for preventing fluoropyrimidine-related adverse events. Further assessment of DPD phenotyping will require clinical validation in a prospective study. [ABSTRACT FROM AUTHOR]

Abstract Background The SAVVY project aims to improve the analyses of adverse events (AEs) in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). This paper summarizes key features and conclusions from the various SAVVY papers. Methods Summarizing several papers reporting theoretical investigations using simulations and an empirical study including randomized clinical trials from several sponsor organizations, biases from ignoring varying follow-up times or CEs are investigated. The bias of commonly used estimators of the absolute (incidence proportion and one minus Kaplan-Meier) and relative (risk and hazard ratio) AE risk is quantified. Furthermore, we provide a cursory assessment of how pertinent guidelines for the analysis of safety data deal with the features of varying follow-up time and CEs. Results SAVVY finds that for both, avoiding bias and categorization of evidence with respect to treatment effect on AE risk into categories, the choice of the estimator is key and more important than features of the underlying data such as percentage of censoring, CEs, amount of follow-up, or value of the gold-standard. Conclusions The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. Whenever varying follow-up times and/or CEs are present in the assessment of AEs, SAVVY recommends using the Aalen-Johansen estimator (AJE) with an appropriate definition of CEs to quantify AE risk. There is an urgent need to improve pertinent clinical trial reporting guidelines for reporting AEs so that incidence proportions or one minus Kaplan-Meier estimators are finally replaced by the AJE with appropriate definition of CEs.

The 2020 onset of the COVID-19 pandemic globally strained healthcare. Healthcare systems worldwide had to rapidly reorganize, impacting service delivery, patient care, and care-seeking behaviors. This left little time to assess the pandemic's effects on patient safety. This paper investigates COVID-19's influence on patient safety in a Danish region, using data from the national reporting system for adverse events during the initial COVID-19 surge in early 2020. This retrospective analysis investigated how the early phase of the COVID-19 pandemic (January–September 2020) affected the incidence of adverse events in a Danish Region, comparing it to the same period in 2019. Data were sourced from the Danish Patient Safety Database and regional systems. Adverse events were reported numerically. Descriptive statistics were employed to describe the percentage difference in adverse events and hospital activity, as well as the rate of adverse events per 1000 activities. Additionally, COVID-19-specific adverse events from April 2020 to March 2021 were identified and analyzed, categorizing them into seven risk areas across various healthcare sectors. During Denmark's initial COVID-19 surge in early 2020, the North Denmark Region's hospitals reported a significant decrease in adverse events, with a 42.5% drop in March 2020 compared to March 2019. From January to September 2020, the number of adverse events dropped 8.5% compared to the same period in 2019. In the same period, hospital activity declined by 10.2%. The ratio of reported adverse events per 1000 hospital activities thus decreased in early 2020 but showed only a minor difference overall for January–September compared to 2019. Between April 2020 and March 2021, out of 5703 total adverse events, 324 (5.7%) were COVID-19 related. COVID-19-related events were categorized into seven distinct risk areas, reflecting diverse impacts across healthcare sectors including hospitals, general practices, pre-hospital care, and specialized services. The initial decline in reporting of adverse events likely resulted from rapid healthcare changes and under-prioritization of the reporting system during the acute phase. However, a near return to pre-pandemic reporting levels suggests a resilient reporting system despite the crisis. The study's strength lies in the comprehensive data from Danish reporting systems, though it acknowledges potential underreporting and doesn't measure the pandemic's overall impact on patient safety. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-checkpoint inhibitors have been proven to aid in tumor regression. We performed a meta-analysis and systematic review to investigate the relationship between hospital volume and patient outcomes. We found that centers performing ≥ 33 annual cases had fewer cardiac-related adverse events (AEs). The pooled estimated rates of grade 5 AEs were 2.75% (95%CI: 2.18–3.47), with higher annual cases associated with reduced grade 5 AEs at meta-regression. Ultimately, patients should be referred to high-volume centers when severe immune-related AEs occur. Immune-checkpoint inhibitors (ICIs) were proven effective in inducing tumor regression. However, its toxicity tends to be fatal. We sought to investigate the hospital volume/outcomes relationship. Databases were searched for studies reporting immune-checkpoint inhibitors adverse events (AEs) in patients with solid-organ malignancies. The outcomes were A) the pooled events rate (PER) of grade 5, grade 3–4, cardiac-related, and pulmonary-related AEs, and B) the assessment of the volume/outcomes relationship. One hundred and forty-seven studies met our inclusion criteria. The PER of grade 5, grade 3–4, and any-grade AEs was 2.75% (95%CI: 2.18–3.47), 26.69% (95%CI: 21.60–32.48), and 77.80% (95%CI: 70.91–83.44), respectively. The PER of pulmonary-related AEs was 4.56% (95%CI: 3.76–5.53). A higher number of annual cases per center was significantly associated with reduced grade 5 (p = 0.019), grade 3–4 (p = 0.004), and cardiac-related AEs (p = 0.035) in the meta-regression. In the current era of cancer immunotherapy, knowledge regarding the early diagnosis and management of immunotherapy-related AEs is essential. Our meta-analysis demonstrates the importance of center volume in improving outcomes and reducing the incidence of severe AEs. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life‐threatening immune checkpoint inhibitor‐related pneumonitis (ICI‐pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI‐pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X‐ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI‐pneumonitis. Additionally, it is tried to differentiate ICI‐pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID‐19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help. [ABSTRACT FROM AUTHOR]

Background Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective. Methods A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021. Results Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded "severe" were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database. Conclusions HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218. [ABSTRACT FROM AUTHOR]

Background: Adverse incidents are well studied within acute care settings, less so within aged care homes. The aim of this scoping review was to define the types of adverse incidents studied in aged care homes and highlight strengths, gaps, and challenges of this research. Methods: An expanded definition of adverse incidents including physical, social, and environmental impacts was used in a scoping review based on the PRISMA Extension for Scoping Reviews Checklist. MEDLINE, CINAHL, and EBSCOhost were searched for English language, peer-reviewed studies conducted in aged care home settings between 2000 and 2020. Forty six articles across 12 countries were identified, charted, and analyzed using descriptive statistics and narrative summary methods. Results: Quantitative studies (n = 42, 91%) dominated adverse incidents literature. The majority of studies focused on physical injuries (n = 29, 63%), with fewer examining personal/interpersonal (15%) and environmental factors (22%). Many studies did not describe the country's aged care system (n = 26, 56%). Only five studies (11%) included residents' voices. Discussion: This review highlights a need for greater focus on resident voices, qualitative research, and interpersonal/environmental perspectives in adverse event research in aged care homes. Addressing these gaps, future research may contribute to better understanding of adverse incidents within this setting. [ABSTRACT FROM AUTHOR]

Background There is a policy drive in NHS maternity services to improve open disclosure with harmed families and limited information on how better practice can be achieved. Objectives To identify critical factors for improving open disclosure from the perspectives of families, doctors, midwives and services and to produce actionable evidence for service improvement. Design A three-phased, qualitative study using realist methodology. Phase 1: two literature reviews: scoping review of post-2013 NHS policy and realist synthesis of initial programme theories for improvement; an interview study with national stakeholders in NHS maternity safety and families. Phase 2: in-depth ethnographic case studies within three NHS maternity services in England. Phase 3: interpretive forums with study participants. A patient and public involvement strategy underpinned all study phases. Setting National recruitment (study phases 1 and 3); three English maternity services (study phase 2). Participants We completed n = 142 interviews, including 27 with families; 93 hours of ethnographic observations, including 52 service and family meetings over 9 months; and interpretive forums with approximately 69 people, including 11 families. Results The policy review identified a shift from viewing injured families as passive recipients to active contributors of post-incident learning, but a lack of actionable guidance for improving family involvement. The realist synthesis found weak evidence of the effectiveness of open disclosure interventions in the international maternity literature, but some improvements with organisation-wide interventions. Recent evidence was predominantly from the United Kingdom. The research identified and explored five key mechanisms for open disclosure: meaningful acknowledgement of harm; involvement of those affected in reviews/investigations; support for families’ own sense-making; psychological safely of skilled clinicians (doctors and midwives); and knowing that improvements to care have happened. The need for each family to make sense of the incident in their own terms is noted. The selective initiatives of some clinicians to be more open with some families is identified. The challenges of an adversarial medicolegal landscape and limited support for meeting incentivised targets is evidenced. Limitations Research was conducted after the pandemic, with exceptional pressure on services. Case-study ethnography was of three higher performing services: generalisation from case-study findings is limited. No observations of Health Safety Investigation Branch investigations were possible without researcher access. Family recruitment did not reflect population diversity with limited representation of non-white families, families with disabilities and other socially marginalised groups and disadvantaged groups. Conclusions We identify the need for service-wide systems to ensure that injured families are positioned at the centre of post-incident events, ensure appropriate training and post-incident care of clinicians, and foster ongoing engagement with families beyond the individual efforts made by some clinicians for some families. The need for legislative revisions to promote openness with families across NHS organisations, and wider changes in organisational family engagement practices, is indicated. Examination of how far the study’s findings apply to different English maternity services, and a wider rethinking of how family diversity can be encouraged in maternity services research. Study registration This study is registered as PROSPERO CRD42020164061. The study has been assessed following RAMESES realist guidelines. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research Programme (NIHR award ref: 17/99/85) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 22. See the NIHR Funding and Awards website for further award information. Plain language summary This study describes the experiences of families and healthcare professionals involved in incidents in NHS maternity care. The incidents caused harm-like injury or death to the baby or woman. We wanted to know whether services involved families in investigations and reviews and how this was done, what worked well, what did not work well and why. To do this, we first looked at what had already been written about ‘open disclosure’ or OD. Open disclosure is when the NHS admits to families that the care they provided has directly caused harm. After open disclosure occurs, families should be involved in making sure that the NHS learns so it can deliver better care for families in the future. In our reading, we found that families want a meaningful apology, to be involved in reviews or investigations, to know what happened to their loved one, to be cared for by knowledgeable doctors and midwives who are supported in providing open disclosure and to know things have changed because of what happened. Recommendations for involving families in open disclosure have improved, but there is still work to be done to make sure families are involved. Next, we talked to over 100 healthcare professionals involved in government policy for open disclosure in maternity services and 27 families who experienced harm. We spent 9 months observing the work of clinicians at three maternity services to watch open disclosure. We shared early findings with families, doctors, midwives and managers, and included their views. We found that services need to provide dedicated time, education and emotional support for staff who provide open disclosure. Services need to ensure that families have ongoing support and better communication about incidents. Finally, families must be involved in the review process if they want to be with their experiences reflected in reports and kept informed of ongoing improvements. Scientific summary Background A range of interventions have been introduced in the UK NHS to improve post-incident communication and support of injured families. However, there is limited evidence on the progress of this work and how improvements in open disclosure (OD) are to be embedded. Study aims and objectives The aim was to identify the critical, underlying factors for improving the incidence and quality of post-incident communication with families in NHS maternity services. This required examination of what is necessary and required in different contexts for OD processes and practices to be strengthened for families, doctors and midwives (henceforth clinicians) and service managers. Following a realist evaluation approach, the study objectives were to: establish initial hypotheses to focus investigation of OD improvements in NHS maternity services in England examine the scope of OD in NHS maternity services from the perspectives of regional and national stakeholders refine our initial hypotheses in relation to the analysis of regional and national stakeholder perspectives conduct an in-depth study of OD improvement within services verify data interpretation and study output development with different stakeholders (families, clinicians, service managers and national policy-makers). Overview of methods A qualitative study using realist evaluation methodology to evaluate the progress of OD in English NHS maternity services was conducted (May 2019–March 2022) in three sequential study phases (SPs). Realist approaches are theory-driven and designed for investigation of complex social interventions. They consider if and how an intervention works in different circumstances from the perspectives of different people. Initial hypotheses, developed from the use of a realist evaluation conceptual tool [context–mechanism–outcome (C–M–O) configurations], are developed from literature synthesis and ‘tested’ by primary research to identify potential causal relationships that explain how an intervention works. A Project Advisory Group (PAG), including families, participated in study decisions, from initial theory development, case-study sampling, data collection and interpretation of study findings against a background of rapid policy change. Primary data collection was from November 2019 to January 2022. A patient involvement and public engagement strategy sought to maximise family involvement in all stages of the study cycle. Study phase1a: literature review A scoping review examined recent (2014–22) policy recommendations for family engagement improvements in NHS maternity services. Documents were identified through database searching and included if they were related to safety, incidents, harm, reviews and investigations in maternity care. Academic papers; essays; conference abstractions, papers and presentations; and research studies were excluded. The realist synthesis of primary evidence of the progress of interventions for strengthening OD in international maternity settings included 38 documents appraised for relevance and rigour. Documents were from key database searches, included all English language sources (post 2000), without predetermined exclusion criteria for research methods. Only primary research evidence or evidence synthesis was included. Programme theories were developed with our PAG for testing during later SPs. Study phase 1b: national and regional stakeholder interview study National and regional stakeholders (n = 44), and families (n = 23), were interviewed following a topic guide developed from our literature synthesis. Families included in the study have histories of significant injury, including the stillbirth, death or serious injury of their baby and/or themselves (dating from 2007 to 2021). Study phase 2: ethnographic case studies Three maternity services in two Trusts were identified for in-depth ethnographic research by purposive sampling, based on their capacity to accommodate research immediately following the coronavirus disease 2019 (COVID-19) pandemic, and evidence of their positive deviance in improvement work on openness identified from public data sets. Across these services, we conducted: staff interviews (n = 75) and three return staff interviews, family interviews (n = 4), observations of staff and family meetings (n = 52) and observations of informal unit and office activities (all observations totalled 93 hours, with 30 hours of in-person observations). Families recruited from the case-study services had histories of significant injury dating from 2018 to 2020. We also collected and analysed locally available documentation relating to candour and being open. Study phase 3: interpretation We conducted five interpretive forums to inform the interpretation of findings. These were a forum with project advisors (n = 14), including families (n = 6), a family forum with several SP1b study participants (n = 5) and three service case-study forums, comprised of clinical and service managers and clinicians. Total forum participation was approximately n = 65. All data were managed using NVivo 20 (QSR International, Warrington, UK) and analysed concurrently by two researchers using a retroductive approach. This technique involved the ongoing examination and theorisation of findings to identify causal explanations for how, for whom, and in what ways OD might be improved. We used the five programme theories identified from the realist review to organise the analysis and reporting of our stakeholder interview and ethnographic case-study findings. Findings from our forums are included in the synthesis and discussion of findings. Results Literature reviews Our scoping review of policy documents (n = 39) identified a shift from a paternalistic view of injured families as passive recipients of care to active contributors in reviews, investigations, learning and quality improvement. Two overlapping policy trajectories were identified: one related to the Duty of Candour (DoC) and one related to maternity safety more widely. Seven themes were identified: building trust in organisations; improving systems of care and ensuring accountability; improving the safety of maternity care and saying sorry; shifting to individualised, relational care; enhancing communication; conceptualising families as active partners rather than passive recipients; and enabling families to guide the process. Although the progression of how family involvement is discussed and considered in policy is moving in a positive direction, we note the opportunity for future, specific, actionable recommendations to ensure these ideals translate into practice. In the realist synthesis, documents (n = 39) were appraised for ‘fitness-for-purpose’, that together documented primary evidence of 21 OD improvement interventions from which we identified 5 initial programme theories. Interventions documented were predominantly from USA, Australasia, and, more recently, UK sources. We identified limited evidence of the effectiveness of interventions documented. We found a difference between interventions that were adjuncts to more general safety improvement projects, and organisation-wide interventions focused on post-incident communication and care of injured families. Identified programme theories were: receiving a meaningful acknowledgement of the harm that has happened, being involved during the review/investigation process, making sense of what happened, receiving care from clinicians who are skilled and feel psychologically safe during post-incident communication and knowing that things have changed because of what has happened. Findings by programme theory Receiving a meaningful acknowledgement of the harm that has happened National stakeholders described factors that prevented or slowed improvements in initial post-incident communication and ongoing care of injured families. These were: the risks of litigation and reputational damage which may be associated with an apology and the obligation to be candid. This was particularly challenging when the extent or circumstances of injury were uncertain. Variation in the confidence and willingness of clinicians to undertake initial and ongoing disclosure with families was noted across the case studies. Alongside general medicolegal and ethical challenges to disclosure improvements, wider erosion of compassionate disclosure with families in relation to the escalation of organisational compliance in maternity safety initiatives was noted by stakeholders. Interviews with families on their post-incident experiences (2007–11) highlighted an ongoing lack of compassionate care and of prompt disclosure in many services. Many families distrusted post-incident communication, suspecting that information was being withheld. In the case-study services, the main concern for OD leads was the recovery of family trust in the service. Here, the tension between disclosure as a mandated directive and as ongoing communication was notable, with lack of investment and organisational support for the latter. A significant context of OD work was the churn of work schedules and the speed of family transfers. This complicated efforts to develop consistency of communication and care across initial, mandated and ongoing post-incident meetings, particularly where the uniqueness and flux in the needs of harmed families were paramount and families were already distrustful. These conditions led to a situation where OD was sustained as an individual and selective initiative conducted by some clinicians with some families. Being involved during the review/investigation process We examined experiences of the implementation of family engagement through the Perinatal Mortality Review Tool (PMRT) and independent Health Safety Investigation Branch (HSIB) reviews/investigations from national, in-depth, case-study perspectives. We found PMRT implementation sometimes lacked relational care for families. Additionally, families were sometimes suspicious of the independence of external incident reviews. The case-study services reported inadequacies in family inclusion, with limited proactive approaches to family involvement. A range of family involvement approaches and rationales for involvement were found across and within the case-study services, with an emphasis on families as contributing value to organisational learning for safety improvement. The tension felt by clinicians between sharing uncertain knowledge of an incident with a family and sustaining OD is identified, as is the tension between the different goals of families and services, with the former desiring answers about their case and the latter seeking system-based learning for ongoing safety improvement. Making sense of what happened We explore the practices of knowledge construction in incidents and the management of this knowledge from the perspectives of national stakeholders, staff and families. The impact of widespread organisational defensiveness over documentation sent to families, along with confusion over the purpose of reports, generated distrust. Nationally, the poor quality or inaccuracies in clinical records exacerbated differences between service and family perspectives. In the crafting of reports, during ongoing family debriefings on report findings and through informal avenues and networks, the support for families to make sense of what happened could sometimes be recovered. However, we identify the privilege and capacity required for families to gather information and garner personal networks and expertise independently of services for this to take place. Receiving care from clinicians who are skilled and feel psychologically safe during post-incident communication We identified a national underinvestment in the training of clinicians in the care of injured families and in specialist OD skills. Interviews with junior clinicians, including Band 5/6 midwives; obstetric trainees and clinical fellows, highlighted the importance of early, non-judgemental, post-incident support for junior staff. The ongoing impact of avoidable harm on clinicians is examined, along with the impact of the limited involvement of staff in Trust-level investigation and review processes. We mapped the organisation and reported use of post-incident staff support for the three case-study services and found that debriefs, organised within a few weeks of the incident, and opportunities for meeting with families were most valued by staff. Services designed or commissioned by organisations without consultation with front-line staff themselves were underused and there was also a tendency for expert clinicians to see OD work as a personal rather than a professional or service imperative. Knowing that things have changed because of what has happened The importance for injured families and staff involved in an incident to see learning and service change following an incident was clear in national and case-study findings. Demonstrating that changes were in progress was key to a service demonstrating trustworthiness to the injured family. Some injured families felt a personal responsibility to ensure that change was secured. However, in most cases, services did not maintain contact with families after their review or investigation debriefs. For some clinical leads, there was a tension between ‘quick wins’ and protracted, significant, service investment. For wider staff groups, there was a lack of effective service-level communication strategies for updating on learning and change from incidents. Embedded, ongoing multidisciplinary team meetings, where non-judgemental discussion of incidents and their effects could take place, were identified as important for establishing a wider culture of openness. The extent and tone of clinical governance (CG) outreach to front-line staff were also significant in shaping staff attitudes and behaviours towards incidents and harmed families. Discussion Realist analysis identified the significant factors and contexts that impacted efforts to strengthen OD in maternity care. We explored several layers of context influencing the progress of this work. Nationally, we identified an ongoing tension between policy prompting OD and a medicolegal context where this openness continued to place clinicians and services at reputational or legal risk. Trust-level clinical leadership and the maturation of related service approaches (notably, family and patient involvement expertise and access to post-pregnancy support pathways) played a significant role in supporting OD. For families, variations in post-incident communication and care depended on two main factors: first, the assignment of an incident to one or more national maternity safety improvement programmes that entailed particular expectations of, and processes for, family involvement, and second, the capacity of a family to proactively seek out explanations and to foster relationships for personalised support from some clinicians. In the case-study services, where some harmed families were proactive in demanding a hearing and ongoing care, and where individual clinicians reached personal judgements on a family’s entitlement to this, examples of improved OD were observed. Overall, variations in post-incident communication and support for families were explained by a lack of service investment and by individual differences in attitudes to risk and family entitlement from clinicians. Conclusions This study is the first to establish a national overview and in-depth analysis of the progress of interventions intended to support OD with families. It provides an evidence base of experiences of harmed families (incidents ranging from 2007 to 2021) and of clinicians and managers working in this field (2020–1). There are growing calls for service-level improvements in responsiveness to the experiences and needs of families post incident as well as to their calls for greater openness. However, we find that without dedicated investment in and focus on the post-incident care of families and the emotional and organisational demands of this work on clinicians; without an understanding of these needs by external agencies incentivising improvement; and without national revision in the medicolegal landscape where this work happens, candour about harm in health care will continue to divide the interests of families, staff and services. Research gaps and recommendations Research was conducted immediately after the COVID-19 pandemic, with services under considerable strain. Three high-performing services were recruited for the observational research; therefore, generalisation from findings is limited. Access to observe external (HSIB) investigations was not possible. Despite ongoing revisions to the patient and public involvement (PPI) strategy, families often marginalised by maternity services remain under-represented in this study. A multi-methods study across English maternity services to establish the validity of findings and family recruitment strategies ensuring diversity are recommended for the future. Study registration This study is registered as PROSPERO CRD42020164061. The study has been assessed following RAMESES realist guidelines. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research Programme (NIHR award ref: 17/99/85) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 22. See the NIHR Funding and Awards website for further award information.

The purpose of this paper is to renew interest and attention to the medical history, prescription, and/or use of drugs during dental practice. The work analyzes the issue of the use of drugs in dentistry from both a clinical and a medical–legal point of view. The laws governing the matter were also taken into consideration, relating them to the roles of prescriber and user that the dentist can acquire. Analysis of various aspects of this matter demonstrates that it is necessary for dentists to know the drugs and medical substances, their characteristics and properties, related effects, and interactions in order to use them appropriately and adequately. Knowledge of interferences, reactions, and adverse events or complications helps to reduce errors and protect patients' health. Furthermore, knowledge of the national and international reference standards relating to the use of drugs leads to a reduction in medico–legal questions. In conclusion, knowledge and adequate and appropriate use of drugs reduces the possibility of accidents, adverse events, medico–legal consequences, and disputes with patients. Documented and traceable choices allow the analysis and valuation of professional conduct. Authors perceived the topic of informed consent of patients as relevant to the adequate procedure of prescribing drugs related to dentistry practice; therefore, representative conditions of patients at risk should be illustrated in practice. Legal duties related to physician drug prescription and use must be considered and carefully checked. [ABSTRACT FROM AUTHOR]