Classification of Itch.

Curr Probl Dermatol. 2016;50:1-4

Authors: Ständer S

Abstract
Chronic pruritus has diverse forms of presentation and can appear not only on normal skin [International Forum for the Study of Itch (IFSI) classification group II], but also in the company of dermatoses (IFSI classification group I). Scratching, a natural reflex, begins in response to itch. Enough damage can be done to the skin by scratching to cause changes in the primary clinical picture, often leading to a clinical picture predominated by the development of chronic scratch lesions (IFSI classification group III). An internationally recognized, standardized classification system was created by the IFSI to not only aid in clarifying terms and definitions, but also to harmonize the global nomenclature for itch.

PMID: 27578063 [PubMed - indexed for MEDLINE]

Novel melanoma therapies and their side effects.

Cutis. 2016 Jun;97(6):426-8

Authors: González N, Ratner D

Abstract
In the last few years, melanoma treatment has been revolutionized by the development of immune checkpoint-blocking antibodies or immune checkpoint inhibitors including ipilimumab, vemurafenib, dabrafenib, trametinib, nivolumab, and pembrolizumab. Although they have shown promising results, they also have caused multiple adverse events (AEs), particularly immune-related AEs (irAEs). Specialists should be familiar with these AEs.

PMID: 27416087 [PubMed - indexed for MEDLINE]

Study of warfarin utilization in hospitalized patients: analysis of possible drug interactions.

Int J Clin Pharm. 2016 Oct;38(5):1048-51

Authors: Guidoni CM, Camargo HP, Obreli-Neto PR, Girotto E, Pereira LR

Abstract
Background Drug-drug interactions in patients taking warfarin may contribute to a higher risk of adverse events. Objective To identify and evaluate the prevalence and characteristics of potential DDIs with warfarin. Methods A cross-sectional study was performed in a Brazilian tertiary hospital. The electronic prescriptions of the patients receiving warfarin between January 2004 and December 2010 were analyzed. Socio-demographic, clinical, and therapeutic variables were collected. Warfarin drug-drug interactions were classified as either risk A, B, C, D, or X according to the Lexi-Interact™ Online database. Results A total of 3048 patients were identified who were prescribed warfarin. Of the 154,161 total drug prescriptions issued, 42,120 (27.3 %) were for warfarin. Evaluation of the prescriptions showed that 63.1 and 0.1 % of patients received concomitant drugs classified as having class D or X risk. It was found that 20,539 (48.7 %) prescriptions had at least one drug with a D or X risk. Patients were prescribed an average of 1.4 (±0.4) concomitant medications with a class D or X warfarin-DDI risk, the most frequent being acetylsalicylic acid and amiodarone. Conclusion The results demonstrate a high prevalence of concomitant drug prescriptions with the potential for clinically relevant DDIs with warfarin, the most frequent being acetylsalicylic acid and amiodarone.

PMID: 27365092 [PubMed - indexed for MEDLINE]

[The new drugs of 2014: what is worthwile saving].

Assist Inferm Ric. 2015 Jul-Sep;34(3):154-8

Authors:

PMID: 26488932 [PubMed - indexed for MEDLINE]

[Incidence, management and costs of adverse effects in chronic hepatitis C patients on triple therapy with telaprevir or boceprevir: first 12 weeks of treatment].

Enferm Infecc Microbiol Clin. 2015 May;33(5):331-6

Authors: Guglieri-López B, Ventura-Cerdá JM, Gómez-Álvarez S, Climente-Martí M

Abstract
INTRODUCTION: The aim of the study was to analyze the incidence, management and cost associated to hematological and dermatological adverse effects (AE) in chronic hepatitis C patients on triple therapy (TT) with telaprevir (TVR) or boceprevir (BOC).
METHODS: An analysis was made on the data recorded on patients who started treatment with TVR or BOC associated with peginterferon alfa and ribavirin in a 12-week follow-up period.
RESULTS: Fifty-three patients were included (TVR n=36; BOC n=17). Thrombocytopenia (83% TVR vs. 88% BOC) followed by neutropenia (89% TVR vs. 82% BOC) were the most common AE. Dermatological AE were observed in 32% of patients. Eleven patients required treatment discontinuation (all of them received TVR), and toxicity was the main reason for discontinuation (64%). The percentage of patients who required supportive treatment for management of AE was 66%. The most used supportive treatment was erythropoietin. Eight patients required emergency health care, and 2 were hospitalized due to AE. Total cost of additional supportive resources was 32,522€ (625 [SD=876]€/patient) (TVR 759 [SD=1,022]€/patient vs. BOC 349 [SD=327]€/patient; P>.05). Patients with gradeiii-iv toxicity required greater supportive care with higher costs, compared to patients with gradei-ii toxicity (849 [SD=1,143]€/patient vs. 387 [SD=397]€/patient; P=.053).
CONCLUSION: The addition of new protease inhibitors to conventional treatment leads to a higher incidence of hematological AE in our study, compared to data described in clinical trials. The elevated incidence of AE involves the use of supportive care, increasing total costs of therapy.

PMID: 25128462 [PubMed - indexed for MEDLINE]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

These pubmed results were generated on 2017/04/18

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Interferon-α for Induction and Maintenance of Remission in Eosinophilic Granulomatosis with Polyangiitis: A Single-center Retrospective Observational Cohort Study.

J Rheumatol. 2017 Apr 15;:

Authors: Seeliger B, Förster M, Happe J, Forberg T, Moeser A, Neumann T, Kroegel C

Abstract
OBJECTIVE: Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by frequent relapses following induction therapy. Interferon-α (IFN-α) can reverse the underlying Th2-driven immune response and has successfully induced remission in previous reports. We undertook this study to investigate its efficacy and safety in patients with EGPA.
METHODS: We conducted a retrospective monocentric cohort study including 30 patients (16 women) with active EGPA under IFN-α treatment. Primary endpoints were remission induction, occurrence of relapses, prednisolone (PSL) dosage at time of remission, and adverse events. Remission was defined by a Birmingham Vasculitis Activity Score (BVAS) of 0. Pulmonary function tests were recorded at baseline and at time of remission. Health-related quality of life was analyzed by questionnaire at baseline and following 12 months of treatment.
RESULTS: At baseline, the median BVAS was 6 (interquartile range 4-13.5) and remission or partial response was achieved in 25/30 patients. After initiation of IFN-α treatment, the median PSL dosages could be reduced from 17.5 mg/day at baseline to 5.5 mg/day at time of remission. Following remission, 17 relapses (5 major) in 16 patients were observed. Pulmonary function tests improved and the time of hospitalization decreased. Adverse events at initiation of treatment were common, but mostly transient. Severe adverse events occurred during treatment in 4 patients (autoimmune hepatitis, n = 1; drug-induced neuropathy, n = 3).
CONCLUSION: IFN-α treatment results in high rate of remission and maintenance in EGPA with significant reduction in oral corticosteroids, although reversible adverse events may occur. IFN-α represents an alternative therapeutic option in cases of refractory to standard treatment.

PMID: 28412705 [PubMed - as supplied by publisher]

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 1-Mechanisms, Efficacy, and Safety.

AJNR Am J Neuroradiol. 2017 Apr 13;:

Authors: McNamara C, Sugrue G, Murray B, MacMahon PJ

Abstract
Imaging for the diagnosis and follow-up of patients with suspected or confirmed multiple sclerosis is a common scenario for many general radiologists and subspecialty neuroradiologists. The field of MS therapeutics has rapidly evolved with multiple new agents now being used in routine clinical practice. To provide an informed opinion in discussions concerning newer MS agents, radiologists must have a working understanding of the strengths and limitations of the various novel therapies. The role of imaging in MS has advanced beyond monitoring and surveillance of disease activity to include treatment complications. An understanding of the new generation of MS drugs in conjunction with the key role that MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse events is of vital importance to the radiologist and clinical physician alike. Radiologists are in a unique position to detect many of the described complications well in advance of clinical symptoms. Part 1 of this review outlines recent developments in the treatment of MS and discusses the published clinical data on the efficacy and safety of the currently approved and emerging therapies in this condition as they apply to the radiologist. Part 2 will cover pharmacovigilance and the role the neuroradiologist plays in monitoring patients for signs of opportunistic infection and/or disease progression.

PMID: 28408630 [PubMed - as supplied by publisher]

New drugs, new toxicities: severe side effects of modern targeted and immunotherapy of cancer and their management.

Crit Care. 2017 Apr 14;21(1):89

Authors: Kroschinsky F, Stölzel F, von Bonin S, Beutel G, Kochanek M, Kiehl M, Schellongowski P, Intensive Care in Hematological and Oncological Patients (iCHOP) Collaborative Group

Abstract
Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity. Cytokine-release syndrome (CRS) describes a complex of symptoms including fever, hypotension, and skin reactions as well as lab abnormalities. CRS may occur after the infusion of monoclonal or bispecific antibodies (MABs, BABs) targeting immune effectors and tumor cells and is a major concern in recipients of chimeric antigen receptor (CAR) modified T lymphocytes as well. BAB and CAR T-cell treatment may also be compromised by central nervous system (CNS) toxicities such as encephalopathy, cerebellar alteration, disturbed consciousness, or seizures. While CRS is known to be induced by exceedingly high levels of inflammatory cytokines, the pathophysiology of CNS events is still unclear. Treatment with antibodies against inhibiting immune checkpoints can lead to immune-related adverse events (IRAEs); colitis, diarrhea, and endocrine disorders are often the cause for ICU admissions.Respiratory distress is the main reason for ICU treatment in cancer patients and is attributable to infectious agents in most cases. In addition, some of the new drugs are reported to cause non-infectious lung complications. While drug-induced interstitial pneumonitis was observed in a substantial number of patients treated with phosphoinositol-3-kinase inhibitors, IRAEs may also affect the lungs.Inhibitors of angiogenetic pathways have increased the antineoplastic portfolio. However, vessel formation is also essential for regeneration and tissue repair. Therefore, severe vascular side effects, including thromboembolic events, gastrointestinal bleeding or perforation, hypertension, and congestive heart failure, compromise antitumor efficacy.The limited knowledge of the pathophysiology and management of life-threatening complications relating to new cancer drugs presents a need to provide ICU staff, oncologists, and organ specialists with evidence-based algorithms.

PMID: 28407743 [PubMed - in process]

Efficacy and safety of a four-drug fixed-dose combination regimen versus separate drugs for treatment of pulmonary tuberculosis: a systematic review and meta-analysis.

Braz J Microbiol. 2017 Apr - Jun;48(2):198-207

Authors: Lima GC, Silva EV, Magalhães PO, Naves JS

Abstract
INTRODUCTION: Tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance.
OBJECTIVE: To determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis.
METHODS: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS: In pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5)=1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment.
CONCLUSIONS: The reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels.

PMID: 28063922 [PubMed - indexed for MEDLINE]

Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination.

Clin Vaccine Immunol. 2016 08;23(8):664-71

Authors: Garman L, Smith K, Muns EE, Velte CA, Spooner CE, Munroe ME, Farris AD, Nelson MR, Engler RJ, James JA

Abstract
Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs. AEs appear to be correlated with certain demographic factors, but the underlying immunologic pathways are poorly understood. We evaluated a cohort of 2,421 AVA vaccinees and found 153 (6.3%) reported an AE. Females were more likely to experience AEs (odds ratio [OR] = 6.0 [95% confidence interval {CI} = 4.2 to 8.7]; P < 0.0001). Individuals 18 to 29 years of age were less likely to report an AE than individuals aged 30 years or older (OR = 0.31 [95% CI = 0.22 to 0.43]; P < 0.0001). No significant effects were observed for African, European, Hispanic, American Indian, or Asian ancestry after correcting for age and sex. Additionally, 103 AEs were large local reactions (LLRs), whereas 53 AEs were systemic reactions (SRs). In a subset of our cohort vaccinated 2 to 12 months prior to plasma sample collection (n = 75), individuals with LLRs (n = 33) had higher protective-antigen (PA)-specific IgE levels than matched, unaffected vaccinated individuals (n = 50; P < 0.01). Anti-PA IgE was not associated with total plasma IgE, hepatitis B-specific IgE, or anti-PA IgG in individuals who reported an AE or in matched, unaffected AVA-vaccinated individuals. IP-10 was also elevated in sera of individuals who developed LLRs (P < 0.05). Individuals reporting SRs had higher levels of systemic inflammation as measured from C-reactive protein (P < 0.01). Thus, LLRs and SRs are mediated by distinct pathways. LLRs are associated with a vaccine-specific IgE response and IP-10, whereas SRs demonstrate increased systemic inflammation without a skewed cytokine profile.

PMID: 27280620 [PubMed - indexed for MEDLINE]

Pharmacokinetic comparison using two tablets of an evogliptin/metformin XR 2.5/500 mg fixed dose combination vs. 1 tablet each of evogliptin 5 mg and metformin XR 1,000 mg
.

Int J Clin Pharmacol Ther. 2017 Apr 13;:

Authors: Yoon S, Rhee SJ, Park SI, Yoon SH, Cho JY, Jang IJ, Lee S, Yu KS

Abstract
OBJECTIVES: The aim of this study was to compare the pharmacokinetic (PK) characteristics of evogliptin and metformin following the administration of 2 evogliptin/metformin extended-release (XR) 2.5/500 mg FDC tablets with the coadministration of separate evogliptin 5-mg and metformin XR 1,000-mg tablets (separate formulations).
METHODS: A randomized, two-period, two-sequence crossover study was conducted. Subjects were randomly assigned to receive 2 FDC tablets or the individual tablets, followed by a 14-day washout period and the administration of the alternate treatment. Blood samples were collected predose and up to 72 hours postdose for each period. PK parameters including Cmax and AUClast were calculated. The geometric mean ratios (GMRs) and the 90% confidence intervals (CIs) between FDC and the separate formulations were calculated for the Cmax and AUClast of evogliptin and metformin.
RESULTS: 33 subjects completed the study. The GMR (90% CI) values of Cmax and AUClast for evogliptin were 1.011 (0.959 - 1.066) and 1.010 (0.977 - 1.043), respectively. The GMR (90% CI) values of Cmax and AUClast for metformin were 0.892 (0.827 - 0.963) and 0.893 (0.841 - 0.947), respectively. There was no significant difference between the FDC and separate formulations regarding the occurrence of adverse events. All drug-related adverse events were considered to be mild and resolved without any treatment.
CONCLUSIONS: Two FDC tablets of evogliptin/metformin XR 2.5/500 mg showed a similar PK profile to the separate formulations of evogliptin 5 mg and metformin XR 1,000 mg. All of the 90% CIs of GMR satisfied the regulatory bioequivalence criteria of 0.800 - 1.250.
.

PMID: 28406090 [PubMed - as supplied by publisher]

Clinical and microscopic characteristics of canine toxic epidermal necrolysis.

Vet Pathol. 2015 Mar;52(2):321-30

Authors: Banovic F, Olivry T, Bazzle L, Tobias JR, Atlee B, Zabel S, Hensel N, Linder KE

Abstract
Canine toxic epidermal necrosis (TEN), a rare and life-threatening cutaneous drug reaction, traditionally has been described as full-thickness devitalization of the epidermis with minimal dermal inflammation; however, few reports detail the histologic findings. We characterize the clinical features and histologic variations of 3 canine TEN patients. Clinically, irregular erythematous and purpuric macules evolved into widespread and severely painful erosions. The number of eroded mucosae varied; however, periocular and perilabial mucocutaneous junctions frequently were affected. Thirteen of 17 biopsies were evaluated. Apoptosis at multiple epidermal levels was the most common pattern of epidermal necrosis (12/13 biopsies, 92%). In contrast, full-thickness coagulation necrosis was present less often (7/13 biopsies, 52%). Lymphocytic interface dermatitis was the predominant inflammatory pattern, and intraepidermal lymphocytes, along with fewer histiocytes, were present to some degree in all samples along with lymphocytic satellitosis of apoptotic keratinocytes. The sequence of changes points to lymphocyte-mediated keratinocyte apoptosis as an early step in lesion development with subsequent variation in progression to coagulation necrosis among patients. Histopathologic changes overlapped with those reported for erythema multiforme, in contrast to traditional histologic descriptions of canine TEN. A specific algorithm for assessment of drug causality in epidermal necrolysis (ALDEN) was applied for each patient; carprofen was associated with a probable score for causality in 1 dog. Clinicians should be encouraged to take multiple biopsies in TEN suspect cases as nearly 25% of all biopsies lacked epithelium and were not diagnostic.

PMID: 24907312 [PubMed - indexed for MEDLINE]

Comparison of documentation of patient reported adverse drug reactions on both paper-based medication charts and electronic medication charts at a New Zealand hospital.

N Z Med J. 2016 Oct 28;129(1444):90-96

Authors: Shen W, Wong B, Chin JY, Lee M, Coulter C, Braund R

Abstract
AIM: Known adverse drug reactions (ADRs) can have profound effects on disease states, as well as prescribing practice. Therefore, the correct and complete documentation of each individual patient's ADR history, upon hospital admission, is important in optimising that individual patient's pharmacotherapy. This study investigated the documentation of ADRs at a tertiary New Zealand hospital, on both paper-based medication charts and electronic medication charts to quantify both the number of ADRs patients self-report, as well as the differences between recording of that information in electronic and paper-based charting systems.
METHOD: Following ethical approval, inpatient medication charts on the general medical ward (electronic prescribing), or the general surgical ward (paper-based medication charts) were viewed for documented ADRs-as reported by each patient on admission. Consecutive patient charts (and electronic clinical management system) were viewed until 50 patients from each ward, each with at least one documented ADR, (in any of the information sources) were obtained. Patient demographic information, ADR history and discrepancies between information sources were determined.
RESULTS: In both wards 114 patients were reviewed in order to find 50 patients with documented ADRs. In the medical ward (electronic) 44 (90%) patients had discrepancies in ADR information between different information sources and in the surgical ward (paper) this occurred in 49 (98%) patients.
CONCLUSION: A large number of patients self-report ADRs. Full documentation of patient reported ADRs is required to adequately inform future prescribing decisions. Discrepancies between ADR information recorded in different information systems exist, but information sharing between electronic and non-electronic sources could be prioritised in order to allow full and complete information to be collected, stored and utilised; and reduce the current inadequacies.

PMID: 27806032 [PubMed - indexed for MEDLINE]

Incidence of Antipsychotic-Associated Side Effects: Impact of Clinician Versus Patient Ratings and Change Versus Absolute Scores.

J Clin Psychopharmacol. 2016 Dec;36(6):593-596

Authors: Takeuchi H, Fervaha G, Remington G

Abstract
OBJECTIVE: This study aimed to compare (1) the detection rates of antipsychotic-associated side effects between clinician and patient ratings and (2) differences as a function of change and absolute score definitions.
METHODS: Data from phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (N = 1460) were analyzed. In this trial, 18 adverse events were systematically and concurrently assessed by clinicians and patients using a 4-point severity scale ranging from 0 (absent) to 3 (severe). The incidence of antipsychotic-associated side effects was calculated according to 2 definitions: change score (ie, higher score on the scale versus baseline) and absolute score (a score of 2 or 3 on the scale). In addition, patient and clinician concurrent detection rates were examined.
RESULTS: The differences in incidence of antipsychotic-associated side effects between clinician and patient ratings were as small as 5.7% across the 2 definitions. The incidence of all side effects across clinician and patient ratings was approximately 2 times higher when using the change versus absolute score definition. Among the side effects detected by patients, 11 side effects were identified more frequently by clinicians, with 14.3% to 30.2% differences when using the change versus absolute score definition. Conversely, there was no difference of 10% or greater in patient or clinician concurrent detection rate on any item when using the absolute versus change score definition.
CONCLUSIONS: Our findings suggest that patient ratings are in line with clinician ratings and that the change score definition may be superior for the assessment of antipsychotic-associated side effects in clinical studies.

PMID: 27626285 [PubMed - indexed for MEDLINE]

Polypharmacy: the challenge for nurses.

Nurs Stand. 2016 May 25;30(39):52-60

Authors: Kaufman G

Abstract
Polypharmacy refers to the prescribing of many medicines for one individual. Polypharmacy is increasingly common as a result of the rise in multimorbidity, use of evidence-based clinical guidelines and care pathways, and a focus on disease prevention. Polypharmacy can be justified and appropriate, but it may also be inappropriate and associated with suboptimal health outcomes and mortality. Polypharmacy is associated with adverse drug events such as drug-drug interactions and adverse drug reactions (ADRs). Taking multiple medicines can adversely affect adherence, resulting in lost opportunities for health gain and wasted medicines. Older people, and particularly those who are frail, are susceptible to the adverse effects of polypharmacy. Medication reviews should be undertaken regularly in older people with polypharmacy. Medicines management systems, research, and education are essential to improve safe practice in the management of polypharmacy.

PMID: 27224631 [PubMed - indexed for MEDLINE]

Patient Safety and End-of-Life Care: Common Issues, Perspectives, and Strategies for Improving Care.

Am J Hosp Palliat Care. 2016 Sep;33(8):791-6

Authors: Dy SM

Abstract
The current state of the science in the fields of patient safety and palliative and end-of-life care have many issues in common. This article synthesizes recent systematic reviews and additional research on improving patient safety and end-of-life care and compares each field's perspective on common issues, both in traditional patient safety frameworks and in other areas, and how current approaches in each field can inform the other. The article then applies these overlapping concepts to a key example area: improving documentation of patient preferences for life-sustaining treatment. The synthesis demonstrates how end-of-life issues should be incorporated into patient safety initiatives. In addition, evaluating overlap and comparable issues between patient safety and end-of-life care and comparing different perspectives and improvement strategies can benefit both fields.

PMID: 25877945 [PubMed - indexed for MEDLINE]

From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: A translational overview.

Antioxid Redox Signal. 2017 Apr 11;:

Authors: Tocchetti CG, Cadeddu C, Di Lisi D, Femminò S, Madonna R, Mele D, Monte I, Novo G, Penna C, Pepe A, Spallarossa P, Varricchi G, Zito C, Pagliaro P, Mercuro G

Abstract
SIGNIFICANCE: Antineoplastic therapies have improved the prognosis of oncology patients sig-nificantly. However, these treatments can bring to a higher incidence of side effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is therefore cru-cial for effective cardioprotection, without compromising the efficacy of anti-cancer treat-ments.
CRITICAL ISSUES: CTX can occur within a few days or many years after treatment. Type I CTX is associated with irreversible cardiac cell injury, and is typically caused by anthracyclines and traditional chemotherapeutics. Type II CTX is generally caused by novel biologics and more targeted drugs, and is associated with reversible myocardial dysfunction. Therefore, patients undergoing anti-cancer treatments should be closely monitored, and patients at risk of CTX should be identified before beginning treatment to reduce CTX-related morbidity.
FUTURE DIRECTIONS: Genetic profiling of clinical risk factors and an integrated approach using molecular, imaging, and clinical data may allow the recognition of patients at high-risk of de-veloping chemotherapy-related CTX, and may suggest methodologies to limit damage in a wider range of patients. The involvement of redox mechanisms in cancer biology and anti-cancer treatments is a very active field of research. Further investigations will be necessary to uncover the hallmarks of cancer from a redox perspective and to develop more efficacious antineoplastic therapies that also spare the cardiovascular system.

PMID: 28398124 [PubMed - as supplied by publisher]

Ramucirumab in the treatment of non-small cell lung cancer.

Expert Opin Drug Saf. 2017 Apr 11;:

Authors: Oscar A, Zyanya Lucia ZB, Andres FC, Amir C, Mariana LM

Abstract
INTRODUCTION: Therapeutic options for treating Non-Small Cell Lung Cancer (NSCLC) have recently increased. Ramucirumab (Cyramza), an anti-angionenic agent was approved in 2014 for treatment of several malignancies, including second-line treatment of patients with NSCLC with disease progression on or after platinum-based chemotherapy. Areas covered: We performed a comprehensive search of the literature focused on clinical trials with use of ramucirumab, targeting its evolution in the treatment of NSCLC. This review summarizes the results regarding its safety and efficacy. Expert opinion: Angiogenesis has been widely recognized as a quintessential feature in cancer, intrinsically mediating tumor survival and progression. Ramucirumab, an anti-VEGFR2 agent, combined with docetaxel, was FDA-approved for NSCLC patients. Results from a phase III trial have demonstrated the usefulness of this combination, with benefits in progression free survival and overall survival for NSCLC patients. A greater magnitude of benefit is seen in patients with aggressive tumor behavior. Treatment with ramucirumab is generally tolerable, however, there is potential for severe toxicity. Adverse events reported with this combination include neutropenia, febrile neutropenia and hypertension. Also, there is the intrinsic risk of bleeding resulting from the mechanism of action. As such, adverse events should be identified timely, so drug-related complications can be prevented.

PMID: 28395526 [PubMed - as supplied by publisher]

Drug-Induced Liver Injury.

AACN Adv Crit Care. 2016 Oct;27(4):430-440

Authors: Hamilton LA, Collins-Yoder A, Collins RE

Abstract
Drug-induced liver injury (DILI) can result from both idiosyncratic and intrinsic mechanisms. This article discusses the clinical impact of DILI from a broad range of medications as well as herbal and dietary supplements. Risk factors for idiosyncratic DILI (IDILI) are the result of multiple host, environmental, and compound factors. Some triggers of IDILI often seen in critical care include antibiotics, antiepileptic medications, statins, novel anticoagulants, proton pump inhibitors, inhaled anesthetics, nonsteroidal anti-inflammatory agents, methotrexate, sulfasalazine, and azathioprine. The mechanism of IDILI due to these medications varies, and the resulting damage can be cholestatic, hepatocellular, or mixed. The primary treatment of IDILI is to discontinue the causative agent. DILI due to acetaminophen is intrinsic because the liver damage is predictably aligned with the dose ingested. Acute acetaminophen ingestion can be treated with activated charcoal or N-acetylcysteine. Future areas of research include identification of mitochondrial stress biomarkers and of the patients at highest risk for DILI.

PMID: 27959299 [PubMed - indexed for MEDLINE]