With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate ideas for early recognition of SCAR and to discontinue offending drugs for better management.
Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.
Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using allopurinol.
The scores of accuracy ratings for triage nurses can be improved if factors contributing to inaccuracy can be altered. The findings of this study can be used to guide improvements.
Emergency department (ED) length of stay (LOS) is associated with ED crowding and related complications. Previous studies either analyzed single patient disposition groups or combined different endpoints as a whole. The aim of this study is to evaluate different effects of relevant factors affecting ED LOS among different patient disposition groups.This is a retrospective electronic data analysis. The ED LOS and relevant covariates of all patients between January 2013 and December 2013 were collected. A competing risk accelerated failure time model was used to compute endpoint type-specific time ratios (TRs) for ED LOS.A total of 149,472 patients was included for analysis with an overall medium ED LOS of 2.15 [interquartile range (IQR) = 6.51] hours. The medium LOS for discharged, admission, and mortality patients was 1.46 (IQR = 2.07), 11.3 (IQR = 33.2), and 7.53 (IQR = 28.0) hours, respectively. In multivariate analysis, age (TR = 1.012, P < 0.0001], higher acuity (triage level I vs level V, TR = 2.371, P < 0.0001), pediatric nontrauma (compared with adult nontrauma, TR = 3.084, P < 0.0001), transferred patients (TR = 2.712, P < 0.0001), and day shift arrival (compared with night shift, TR = 1.451, P < 0.0001) were associated with prolonged ED LOS in the discharged patient group. However, opposite results were noted for higher acuity (triage level I vs level V, TR = 0.532, P < 0.0001), pediatric nontrauma (TR = 0.375, P < 0.0001), transferred patients (TR = 0.852, P < 0.0001), and day shift arrival (TR = 0.88, P < 0.0001) in the admission patient group.Common influential factors such as age, patient entity, triage acuity level, or arrival time may have varying effects on different disposition groups of patients. These findings and the suggested model could be used for EDs to develop individually tailored approaches to minimize ED LOS and further improve ED crowding status.
Skin is the largest human organ, our protection against various environmental assaults and noxious agents. Accumulation of these stress events may lead to the formation of skin cancers, including both melanoma and non-melanoma skin cancers. Although modern targeted therapies have ameliorated the management of cutaneous malignancies, a safer, more affordable, and more effective strategy for chemoprevention and treatment is clearly needed for the improvement of skin cancer care. Phytochemicals are biologically active compounds derived from plants and herbal products. These agents appear to be beneficial in the battle against cancer as they exert anti-carcinogenic effects and are widely available, highly tolerated, and cost-effective. Evidence has indicated that the anti-carcinogenic properties of phytochemicals are due to their anti-oxidative, anti-inflammatory, anti-proliferative, and anti-angiogenic effects. In this review, we discuss the preventive potential, therapeutic effects, bioavailability, and structure–activity relationship of these selected phytochemicals for the management of skin cancers. The knowledge compiled here will provide clues for future investigations on novel oncostatic phytochemicals and additional anti-skin cancer mechanisms.
Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.
Background Should all out‐of‐hospital cardiac arrest ( OHCA ) patients be directly transported to cardiac arrest centers ( CAC s) remains under debate. Our study evaluated the impacts of different transport time and destination hospital on the outcomes of OHCA patients. Methods and Results Data were collected from 6655 OHCA patients recorded in the regional prospective OHCA registry database of Taoyuan City, Taiwan, between January 2012 and December 2016. Patients were matched on propensity score, which left 5156 patients, 2578 each in the CAC and non‐ CAC groups. Transport time was dichotomized into <8 and ≥8 minutes. The relations between the transport time to CAC s and good neurological outcome at discharge and survival to discharge were investigated. Of the 5156 patients, 4215 (81.7%) presented with nonshockable rhythms and 941 (18.3%) presented with shockable rhythms. Regardless of transport time, transportation to a CAC increased the likelihoods of survival to discharge (<8 minutes: adjusted odds ratio [aOR], 1.95; 95% CI, 1.11–3.41; ≥8 minutes: aOR, 1.92; 95% CI, 1.25–2.94) and good neurological outcome at discharge (<8 minutes: aOR, 2.70; 95% CI, 1.40–5.22; ≥8 minutes: aOR, 2.20; 95% CI, 1.29–3.75) in OHCA patients with shockable rhythms but not in patients with nonshockable rhythms. Conclusions OHCA patients with shockable rhythms transported to CAC s demonstrated higher probabilities of survival to discharge and a good neurological outcome at discharge. Direct ambulance delivery to CAC s should thus be considered, particularly when OHCA patients present with shockable rhythms.
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