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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: 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]

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]

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]

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]

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]

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]

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]

Introduction: Soft tissue fillers are widely used and are commonly considered to be safe. Nonetheless, adverse events such as late inflammatory reactions (LIRs) are reported for every type of filler. As of the start of the COVID-19 pandemic, LIRs have been reported after SARS-CoV infection or vaccination. In the past, we reviewed these adverse events; however, since then, we faced a wave with the Omicron, and the vaccination programs continued with booster vaccines. We therefore aimed to perform an up-to-date review of the literature on LIRs after COVID-19 infection and vaccination with additional learned lessons from this pandemic. Material and methods: We performed a systematic review on soft tissue filler-related LIRs after SARS-CoV-2 infection or vaccination in line with the PRISMA guidelines. Eligible studies were searched in the database PubMed from 1 August 2021 until 1 June 2023. Data on patient characteristics, filler characteristics, clinical findings, and treatment options were retrieved. Results: A total of 14 papers with in total 52 patients were reported, of which 16 had adverse events after a SARS-CoV-2 infection and 36 after SARS-CoV-2 vaccination. In most cases, it concerned females who had their (mostly temporary) fillers for cosmetic purposes. Symptoms were reported in a matter of hours up to weeks after SARS-CoV-2 vaccination (22 Pfizer, 7 Moderna, 3 AstraZeneca, 3 Sputnik V, and one after Siophram), mostly after the first or second dose but sporadically after a third dose. Most patients were treated in a conservative manner. Discussion: LIRs continue to be reported after SARS-CoV-2 infection and vaccination and are currently also reported for non-mRNA vaccines, for non-temporary fillers, and also after a third dose of the vaccine. Although there are more and more papers on this matter, they remain minor and self-limiting. We therefore still advise patients with soft tissue fillers to remain participated in vaccination programs when needed. Level of evidence: Not gradable. [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]

The use of outpatient parenteral antimicrobial therapy (OPAT) for children has several advantages, including reduced length of hospital stay and costs. A reliable vascular access is key to delivering safe and effective pediatric OPAT. In recent years, midline catheters (MC) have been increasingly used for short-term intravenous antibiotic therapy in children. However, there are no studies investigating the use of MCs in the OPAT setting. The main aim of this paper was to evaluate the success and complications of using MCs for pediatric OPAT. This was a retrospective cohort study from a tertiary academic pediatric hospital. All MCs inserted at the hospital and used for OPAT were eligible for study inclusion. The primary objective was to describe the percentage of patients able to complete OPAT without the need for additional venous access. Forty-one MCs were included in the study. Patient mean (SD) age was 5.9 (4.9) years. In 31 cases (76%, 95% CI 62–86%), the iv therapy could be successfully completed using only the MC. Imbalances between the groups suggested unfavorable outcome for saphenous vein catheters as well as for shorter and smaller-sized catheters. Fourteen patients (34%) were subjected to a MC-related complication. Pain on injection in the MC was the most frequent complication (n = 10, 24%). Conclusion: Midline catheters could be an alternative to central venous access for pediatric OPAT. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase MC success rate. No severe MC-related complication was found. Further randomized studies comparing different catheter types are needed. What is Known: • For selected patients, pediatric outpatient parenteral antimicrobial therapy (OPAT) is safe and provides health-economic, psychosocial, and medical advantages compared to in-hospital care. • A reliable venous access is one of the key factors to the success of OPAT, but this can be a challenge in children. What is New: • Using midline catheters, 76% of patients could complete their intended iv therapy without the need for additional venous access. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase the success rate. • Thirty-four percent of catheters were subject to some kind of complication, the most common being pain on injection in the catheter. [ABSTRACT FROM AUTHOR]

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]

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]

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]

• Background rates of maternal foetal and neonatal adverse events in South Africa have been assessed to support safety assessment of vaccines. • Retrospective review of paper-based medical records is challenging and time-consuming. • Missing data hampered alignment between clinically-reported adverse events and adverse events confirmed with GAIA case definitions. • Brighton Collaboration GAIA case definitions are useful, but some require amendments to improve utilization in real world settings. Background epidemiologic population data from low- and middle-income countries (LMIC), on maternal, foetal and neonatal adverse outcomes are limited. We aimed to estimate the incidence of maternal, foetal and neonatal adverse outcomes at South African maternal vaccine trial sites as reported directly in the clinical notes as well as using the 'Global Alignment of Immunization Safety Assessment in Pregnancy' case definitions (GAIA-CDs). GAIA-CDs were utilized as a tool to standardise data collection and outcome assessment, and the applicability and utility of the GAIA-CDs was evaluated in a LMIC observational study. We conducted a retrospective record review of maternity and neonatal case records for births that occurred in Soweto, Inner City- Johannesburg and Metro-East Cape Town, South Africa, between 1st July 2017 and 30th June 2018. Study staff abstracted data from randomly selected medical charts onto standardized study-specific forms. Incidence (per 100,000 population) was calculated for adverse maternal, foetal and neonatal outcomes, which were identified as priority outcomes in vaccine safety studies by the Brighton Collaboration and World Health Organization. Outcomes reported directly in the clinical notes and outcomes which fulfilled GAIA-CDs were compared. Incidence of outcomes was calculated by combining cases which were either reported in clinical notes by attending physicians and/ or fulfilled GAIA-CDs. Of 9371 pregnant women enrolled, 27·6% were HIV-infected, 19·9% attended antenatal clinic in the 1st trimester of pregnancy and 55·3% had ≥1 ultrasound examination. Fourteen percent of women had hypertensive disease of pregnancy, 1·3% had gestational diabetes mellitus and 16% experienced preterm labour. There were 150 stillbirths (1·6%), 26·8% of infants were preterm and five percent had microcephaly. Data available in clinical notes for some adverse outcomes, including maternal- & neonatal death, severe pre-eclampsia/ eclampsia, were able to fulfil GAIA-CDs criteria for all of the clinically-reported cases, however, missing data required to fulfil other GAIA-CD criteria (including stillbirth, gestational diabetes mellitus and gestational hypertension) led to poor correlation between clinically-reported adverse outcomes and outcomes fulfilling GAIA-CDs. Challenges were also encountered in accurately ascertaining gestational age. This study contributes to the expanding body of data on background rates of adverse maternal and foetal/ neonatal outcomes in LMICs. Utilization of GAIA-CDs assists with alignment of data, however, some GAIA-CDs require amendment to improve the applicability in LMICs. This study was funded by Pfizer (Inc). [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]

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]

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]

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 2014, the Global Alignment on Immunization safety Assessment in pregnancy consortium (GAIA) was formed, with the goal of developing a harmonized, globally‐concerted approach to actively monitor the safety of vaccines in pregnancy. A total of 26 standardized definitions for the classification of adverse events have been developed. The aim of this review was to identify and describe studies undertaken to assess the performance of these definitions. A literature search was undertaken to identify published studies assessing the performance of the definitions, and reference lists were snowballed. Data were abstracted by two investigators and a narrative review of the results is presented. Four studies that have evaluated 13 GAIA case definitions (50%) were identified. Five case definitions have been assessed in high‐income settings only. Recommendations have been made by the investigators to improve the performance of the definitions. These include ensuring consistency across definitions, removal of the potential for ambiguity or variations in interpretation and ensuring that higher‐level criteria are acceptable at lower levels of confidence. Future research should prioritize the key case definitions that have not been assessed in low‐ and middle‐income settings, as well as the 13 that have not undergone any validation. Synopsis: This review paper summarizes the research conducted assessing performance of standardized case definitions developed to actively monitor the safety of maternal vaccines globally. [ABSTRACT FROM AUTHOR]

Objective: If a psychotherapeutic intervention has the capacity to produce positive change, the "deterioration effect" theory holds that it must also have the potential for negative effects. However, the definition, measurement, and reporting of unwanted events in psychotherapy is a topic of ongoing discussion. At present this area is under‐explored in interventions for anorexia nervosa (AN), a severe mental illness associated with high medical and psychiatric risks. The aim of this article was to undertake a systematic review of published randomized controlled trials (RCTs) evaluating psychotherapeutic interventions for AN, and to assess how unwanted events were defined, monitored, and reported alongside the trial's key findings. Method: Using a systematic review methodology, this article identified 23 RCTs through database searches meeting eligibility criteria. Results are presented using a narrative summary approach. Results: Unwanted event reporting varied widely, both regarding definitions of key unwanted events (such as non‐compliance or symptom deterioration) and in the amount of detail captured in each paper. Discussion: The review identified two key issues: firstly, a lack of consistent definitions and unclear causality made it difficult to distinguish between unwanted events, and adverse events caused by the interventions. Secondly, it highlighted the difficulty of defining unwanted events where different studies have different populations and goals. Recommendations are made around how the area of defining, monitoring, and reporting unwanted events in RCTs for AN can be taken forward. Public Significance: Whilst psychotherapies can be effective in treating mental health conditions, negative or unwanted events can sometimes occur. This review explored how RCTs examining psychotherapy for AN report how they monitor the safety of participants, and how they report unwanted events. We found that the reporting was often inconsistent or hard to interpret, and we have made recommendations for how this can be improved in the future. [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]

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]

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: 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]

Simple Summary: Although the deep inferior epigastric perforator flap (DIEP) has become the most frequent autologous flap in breast reconstruction, it remains unclear whether reconstruction should be performed at the same time as the mastectomy or delayed. Therefore, we conducted a meta-analysis to offer an overview of recipient site postoperative complications and help guide practicians toward the ideal timing for breast reconstruction. A pooled analysis using the Mantel and Haenszel methods with a fixed effect model provided results as an odd ratio with a 95% confidence interval. Among most complications including hematoma, infection, fat necrosis, and flap loss, no significant differences were observed. However, delayed wound healing was significantly higher for patients who underwent delayed breast reconstruction. This paper offers evidence that both surgical timings offer similar outcomes and are, therefore, valid surgical strategies. Purpose: The setting regarding the ideal timing for deep inferior epigastric perforator flap (DIEP) reconstruction remains unclear. Immediate breast reconstruction (IBR) is performed at the same time as mastectomy, while delayed breast reconstruction (DBR) is performed at any time after mastectomy except immediately. We compared both strategies to assess whether IBR or DBR should be performed to reduce postoperative adverse events. Methods: A systematic review of PubMed, Embase, Medline, Cochrane, and Web of Science was conducted, aiming at articles comparing the recipient site outcomes of IBR versus DBR with DIEP. We used the Mantel–Haenszel method with a fixed effects model. Results were expressed as the OR with a 95% CI. Results: Two retrospective and two prospective studies were identified involving 5784 DIEPs (1744 immediate and 4040 delayed). We showed a significant difference in favor of IBR for wound healing issues (OR = 0.57, 95% CI 0.41, 0.77; p = 0.0003). However, no significant differences for hematoma, infection, fat necrosis, partial flap loss, and total flap loss rate were seen. Conclusions: Despite variability in the choice of the ideal time for breast reconstruction and outcomes reported among studies, immediate DIEP surgery appears to be a reliable setting with less delayed healing issues. [ABSTRACT FROM AUTHOR]

Background: Healthcare is not without risk. Despite two decades of policy focus and improvement efforts, the global incidence of harm remains stubbornly persistent, with estimates suggesting that 10% of hospital patients are affected by adverse events. Methods: We explore how current investigative responses can compound the harm for all those affected—patients, families, health professionals and organizations—by neglecting to appreciate and respond to the human impacts. We suggest that the risk of compounded harm may be reduced when investigations respond to the need for healing alongside system learning, with the former having been consistently neglected. Discussion: We argue that incident responses must be conceived within a relational as well as a regulatory framework, and that this—a restorative approach—has the potential to radically shift the focus, conduct and outcomes of investigative processes. Conclusion: The identification of the preconditions and mechanisms that enable the success of restorative approaches in global health systems and legal contexts is required if their demonstrated potential is to be realized on a larger scale. The policy must be co‐created by all those who will be affected by reforms and be guided by restorative principles. Patient or Public Contribution: This viewpoint represents an international collaboration between a clinician academic, safety scientist and harmed patient and family members. The paper incorporates key findings and definitions from New Zealand's restorative response to surgical mesh harm, which was co‐designed with patient advocates, academics and clinicians. [ABSTRACT FROM AUTHOR]

Uncertainty surrounding the risk of developing and dying from Thrombosis and Thrombocytopenia Syndrome (TTS) associated with the AstraZeneca (AZ) COVID-19 vaccine may contribute to vaccine hesitancy. A model is urgently needed to combine and effectively communicate evidence on the risks versus benefits of the AZ vaccine. We developed a Bayesian network to consolidate evidence on risks and benefits of the AZ vaccine, and parameterised the model using data from a range of empirical studies, government reports, and expert advisory groups. Expert judgement was used to interpret the available evidence and determine the model structure, relevant variables, data for inclusion, and how these data were used to inform the model. The model can be used as a decision-support tool to generate scenarios based on age, sex, virus variant and community transmission rates, making it useful for individuals, clinicians, and researchers to assess the chances of different health outcomes. Model outputs include the risk of dying from TTS following the AZ COVID-19 vaccine, the risk of dying from COVID-19 or COVID-19-associated atypical severe blood clots under different scenarios. Although the model is focused on Australia, it can be adapted to international settings by re-parameterising it with local data. This paper provides detailed description of the model-building methodology, which can be used to expand the scope of the model to include other COVID-19 vaccines, booster doses, comorbidities and other health outcomes (e.g., long COVID) to ensure the model remains relevant in the face of constantly changing discussion on risks versus benefits of COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

Simple Summary: An unplanned return to the operating room (UROR) is defined as a readmission to the operating room because of a complication or an untoward outcome related to the initial surgery. It has been widely used as an indicator of surgical care quality among hospitals. The aim of this paper is to evaluate the role of URORs after elective oncologic thoracic surgery in a high-volume, oncologic referral center, focusing on risk factors and variables that influence the UROR rate. Our findings disclosed that UROR is an effective and reliable quality indicator in oncologic thoracic surgical care; patients experiencing UROR after elective oncologic thoracic surgery have a higher morbidity and mortality rate when compared to standard thoracic surgery. Patients presenting complications after UROR had been submitted to a significantly longer first procedure, had a significantly longer length of stay and a higher post-operative mortality. Bronchopleural fistula remains the most lethal complication in patients undergoing UROR. Background: An unplanned return to the operating room (UROR) is defined as a readmission to the operating room because of a complication or an untoward outcome related to the initial surgery. The aim of the present report is to evaluate the role of URORs after elective oncologic thoracic surgery. Methods: In the study, 4012 consecutive patients were enrolled; among them, 71 patients (1.76%) had an unplanned return to the operating room. Age, sex, Charlson comorbidity index, induction treatments, type of the first operation, indication to readmission to the operating room and type of second operation, length of stay, complication after reoperation and outcomes were collected. Results: The mean age was 63.3 (SD: 13.0); there were 53 male patients (74.6%); the type of the first procedure was: lower lobectomy (11.3%), middle lobectomy (1.4%), upper lobectomy (22.5%), metastasectomy (5.6%), extrapleural pneumonectomy (4.2%), pneumonectomy (40.9%), pleural biopsy (5.6%) and other procedures (8.5%). Patients presenting complications after UROR had undergone a significantly longer first procedure (p < 0.02), had a longer length of stay (p < 0.001) and had higher post-operative mortality (p < 0.001). Conclusions: The patients experiencing UROR after elective oncologic thoracic surgery have significantly higher morbidity and mortality rates when compared to standard thoracic surgery. Bronchopleural fistula remains the most lethal complication in patients undergoing UROR. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, mostly driven by activating mutations in KIT or PDGFRα oncogenes. The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of GIST resulting in a substantial gain in median overall survival. Nowadays, imatinib, sunitinib, regorafenib, and ripretinib are registered as first, second, third, and fourth-line therapies, and avapritinib is registered specifically for GISTs harboring a PDGFRα exon 18/D842V mutation. As a result, health-related quality of life (HRQoL) has become more relevant for this surviving population, which is increasing in number. In daily clinical practice, the side effects of TKIs and their impact on the daily lives of patients are the main reason for treatment adjustments. Currently, an overview of HRQoL issues and side effects of different TKIs registered for the treatment of GIST is lacking. Background: The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of gastrointestinal stromal tumors (GISTs), resulting in a substantial gain in median overall survival. Subsequently, health-related quality of life (HRQoL) has become more relevant. Here, we systematically review the available literature on HRQoL issues and side effects of different TKIs registered for the treatment of GIST. Methods: A search through five databases was performed. Full reports in English describing HRQoL outcomes and/or side effects in GIST patients on TKI therapy were included. Results: A total of 104 papers were included; 13 studies addressed HRQoL, and 96 studies investigated adverse events. HRQoL in patients treated with imatinib, regorafenib, and ripretinib remained stable, whereas most sunitinib-treated patients reported a decrease in HRQoL. Severe fatigue and fear of recurrence or progression were specifically assessed as HRQoL issues and had a negative impact on overall HRQoL as well as psychological and physical well-being. The majority of studies focused on physician-reported side effects. Nearly all GIST patients treated with a TKI experienced at least one adverse event, mostly mild to moderate. Conclusions: Despite the fact that almost all patients treated with a TKI experienced side effects, this did not seem to affect overall HRQoL during TKI therapy. In daily practice, it are the side effects that hamper a patient's HRQoL resulting in treatment adjustments, suggesting that the reported side effects were underestimated by physicians, or the measures used to assess HRQoL do not capture all relevant issues that determine a GIST patient's HRQoL. [ABSTRACT FROM AUTHOR]

The use of continuous glucose monitoring (CGM) for blood glucose control is increasing and is effective in changing treatment methods and improving lifestyle by identifying problems in blood sugar patterns. However, adverse skin events are increasing due to the insertion of invasive tools or attachment of sensors to the skin for 14 days for intermittent CGM. These adverse events can be the reason for the discontinuation of CGM. Therefore, this paper aims to determine methods to identify and manage skin irritation and side effects caused by CGM accessories. [ABSTRACT FROM AUTHOR]

A 60-year-old man presented with dyspnea four days after the second dose of the coronavirus disease (COVID-19) vaccine. Imaging revealed extensive ground-glass opacification. Blood tests were notable for elevated KL-6 levels. Bronchoalveolar lavage fluid analysis showed increased lymphocyte-dominant inflammatory cells and decreased CD4/CD8 ratio. These findings were consistent with the diagnosis of drug-induced interstitial lung disease (DIILD). To the best of our knowledge, this has never been reported in previous literature. Treatment with glucocorticoids relieved his symptoms. This paper highlights that although extremely rare, COVID-19 vaccine could cause DIILD, and early diagnosis and treatment are crucial to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Allergic respiratory diseases, such as asthma and allergic rhinitis, are global health issues and have had an increasing prevalence in the last decades. Allergen‐specific immunotherapy (AIT) is the only curative treatment for allergic rhinitis and asthma, as it has a disease‐modifying effect. AIT is generally administered by two routes: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). Local side effects are common, but usually well‐tolerated and self‐limited. However, systemic side effects are rare, and associated with uncontrolled asthma and bronchial obstruction, or related to errors in administration. Physicians should constantly assess potential risk factors for not only reporting systemic reactions and fatalities but also implementing other therapies to improve AIT safety. This paper highlights recent evidence on local and systemic reactions related to SCIT and SLIT in children. [ABSTRACT FROM AUTHOR]

Allergic respiratory diseases, such as asthma and allergic rhinitis, are global health issues and have had an increasing prevalence in the last decades. Allergen‐specific immunotherapy (AIT) is the only curative treatment for allergic rhinitis and asthma, as it has a disease‐modifying effect. AIT is generally administered by two routes: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). Local side effects are common, but usually well‐tolerated and self‐limited. However, systemic side effects are rare, and associated with uncontrolled asthma and bronchial obstruction, or related to errors in administration. Physicians should constantly assess potential risk factors for not only reporting systemic reactions and fatalities but also implementing other therapies to improve AIT safety. This paper highlights recent evidence on local and systemic reactions related to SCIT and SLIT in children. [ABSTRACT FROM AUTHOR]

In 2016, the Australian Government legislated to allow cannabis to be prescribed to patients as an unapproved medicine under the special access provisions of the Therapeutic Goods Act. This paper compares the Australian regulatory approach with other national approaches, outlines the main provisions of the Special Access Scheme for medical cannabis, describes how the program has evolved since 2017, includes an analysis of adverse events reported to the Therapeutic Goods Administration, and discusses the barriers that remain for patients who wish to access medical cannabis. It assesses how well the Australian program has addressed the challenges of providing patients with easier access to medical cannabis while ensuring that high-quality products are used safely and effectively under medical guidance. [ABSTRACT FROM AUTHOR]

ICD-11 provides a promising new way to capture healthcare-related harm or injury. In this paper, we elaborate on the framework for describing healthcare-related events where there is a presumed causal link between an event and underlying healthcare-related factors. The three-part model for describing healthcare-related harm or injury in ICD-11 consists of (1) a healthcare-related activity that is the cause of injury or other harm (selected from Chapter 23 of ICD-11); (2) a mode or mechanism of injury or harm, related to the underlying cause (also from Chapter 23 of ICD-11); and (3) the harmful consequences of the event to the patient, selected from any of Chapters 1 through 22 of ICD-11 (most importantly, the injury or harm experienced by the patient). Concepts from these three elements are linked/clustered through postcoordination to reflect the three-part model in a single coded expression. ICD-11 contains many novel features, and the three-part model described here for healthcare-related adverse events is a notable example. [ABSTRACT FROM AUTHOR]