Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are ...arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.
The prescribing cascade revisited Rochon, Paula A; Gurwitz, Jerry H
The Lancet (British edition),
05/2017, Volume:
389, Issue:
10081
Journal Article
Peer reviewed
A prescribing cascade begins when a drug is prescribed, an adverse drug event occurs that is misinterpreted as a new medical condition, and a subsequent drug is prescribed to treat this drug-induced ...adverse event (figure). We first described the idea of a prescribing cascade in The Lancet in 1995,1 and expanded on this concept in The BMJ in 1997.2 The identification and interruption of prescribing cascades is an important, actionable, and underappreciated opportunity to improve medication safety in older people.
COVID-19 remains a deadly disease that poses a serious threat to humanity. COVID-19 vaccines protect the public and limit viral spread. However, public acceptance is significantly dependent on the ...efficacy and side effects (SEs) of the vaccinations being produced. Four important mechanisms have been examined for COVID-19 vaccines: DNA-based, mRNA-based, protein-based, and inactivated viruses. Vaccination safety research was formerly limited to manufacturer-sponsored studies, but numerous additional cross-sectional survey-based studies conducted globally have contributed to the generation of vaccine-related safety data reports. Twenty-seven studies and twenty-four case reports published-up till 2021 were overviewed for the presentation of SEs and their severity. Injection site pain remained the most dominant localized SE, while headache and fatigue were the most prevalent systemic SEs. Most studies reported that all vaccinations were safe, with very little or no adverse effects, but the nature of SEs was reported to be more persistent in DNA- and mRNA-based vaccines, while inactivated viral vaccines were associated with longer-duration SEs. Overall, SEs were found to be more dominant in women and youngsters. Case reports of adverse reactions have also been documented, but there is still a need to find out their pathological linkage with the COVID-19 vaccination.
Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the ...frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia.
We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics.
Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects.
This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.
Immune checkpoint inhibitors are reshaping the prognosis of many cancer and are progressively becoming the standard of care in the treatment of many tumour types. Immunotherapy is bringing new hope ...to patients, but also a whole new spectrum of toxicities for healthcare practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of patients with cancer are increasingly confronted with the therapeutic challenge of treating patients with severe and refractory immune-related adverse events. In this Personal View, we summarise the therapeutic strategies that have been used to manage such toxicities resulting from immune checkpoint inhibitor treatment. On the basis of current knowledge about their pathogenesis, we discuss the use of new biological and non-biological immunosuppressive drugs to treat severe and steroid refractory immune-related adverse events. Depending on the immune infiltrate type that is predominant, we propose a treatment algorithm for personalised management that goes beyond typical corticosteroid use. We propose a so-called shut-off strategy that aims at inhibiting key inflammatory components involved in the pathophysiological processes of immune-related adverse events, and limits potential adverse effects of drug immunosuppression on tumour response. This approach develops on current guidelines and challenges the step-by-step increase approach to drug immunosuppression.
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel ...substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.
Severe cutaneous adverse reactions to drugs Duong, Tu Anh, Dr; Valeyrie-Allanore, Laurence, MD; Wolkenstein, Pierre, Prof ...
The Lancet (British edition),
10/2017, Volume:
390, Issue:
10106
Journal Article
Peer reviewed
Summary During the past decade, major advances have been made in the accurate diagnosis of severe cutaneous adverse reactions (SCARs) to drugs, management of their manifestations, and identification ...of their pathogenetic mechanisms and at-risk populations. Early recognition and diagnosis of SCARs are key in the identification of culprit drugs. SCARS are potentially life threatening, and associated with various clinical patterns and morbidity during the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reactions with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis. Early drug withdrawal is mandatory in all SCARs. Physicians' knowledge is essential to the improvement of diagnosis and management, and in the limitation and prevention of long-term sequelae. This Seminar provides the tools to help physicians in their clinical approach and investigations of SCARs.
Adverse drug reactions (ADRs) result in major health problems in the United States in both the inpatient and outpatient setting. ADRs are broadly categorized into predictable (type A and ...unpredictable (type B) reactions. Predictable reactions are usually dose dependent, are related to the known pharmacologic actions of the drug, and occur in otherwise healthy individuals, They are estimated to comprise approximately 80% of all ADRs. Unpredictable are generally dose independent, are unrelated to the pharmacologic actions of the drug, and occur only in susceptible individuals. Unpredictable reactions are subdivided into drug intolerance, drug idiosyncrasy, drug allergy, and pseudoallergic reactions. Both type A and B reactions may be influenced by genetic predisposition of the patient
The American Society of Regional Anesthesia and Pain Medicine's Third Practice Advisory on local anesthetic systemic toxicity is an interim update from its 2010 advisory. The advisory focuses on new ...information regarding the mechanisms of lipid resuscitation, updated frequency estimates, the preventative role of ultrasound guidance, changes to case presentation patterns, and limited information related to local infiltration anesthesia and liposomal bupivacaine. In addition to emerging information, the advisory updates recommendations pertaining to prevention, recognition, and treatment of local anesthetic systemic toxicity. WHAT'S NEW IN THIS UPDATE?: This interim update summarizes recent scientific findings that have enhanced our understanding of the mechanisms that lead to lipid emulsion reversal of LAST, including rapid partitioning, direct inotropy, and post-conditioning. Since the previous practice advisory, epidemiological data have emerged that suggest a lower frequency of LAST as reported by single institutions and some registries, nevertheless a considerable number of events still occur within the general community. Contemporary case reports suggest a trend toward delayed presentation, which may mirror the increased use of ultrasound guidance (fewer intravascular injections), local infiltration techniques (slower systemic uptake), and continuous local anesthetic infusions. Small patient size and sarcopenia are additional factors that increase potential risk for LAST. An increasing number of reported events occur outside of the traditional hospital setting and involve non-anesthesiologists.
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