Hydrochlorothizide-induced acute generalised exanthematous pustulosis presenting with bilateral periorbital impetigo.

BMJ Case Rep. 2019 Feb 11;12(2):

Authors: Reap LE, Rodd C, Larios J, Marshall M

Abstract
Acute generalised exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterised by the appearance of erythematous plaques and papules with overlying non-follicular pinpoint pustules. Drugs are the cause of AGEP in approximately 90% of cases. The most common causes include anti-infective agents (aminopenicillins, quinolones, antibacterial sulfonamides and terbinafine), antimalarials and diltiazem. To the best of our knowledge, to date there has only been one report of hydrochlorothiazide-induced AGEP. There has never been a case report of losartan-induced AGEP. Here, we present a case of AGEP that is the second case purportedly caused by hydrochlorothiazide.

PMID: 30755424 [PubMed - indexed for MEDLINE]

Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials.

Trials. 2018 Dec 11;19(1):674

Authors: Howick J, Webster R, Kirby N, Hood K

Abstract
BACKGROUND: Trial participants in placebo groups report experiencing adverse events (AEs). Existing systematic reviews have not been synthesized, leaving questions about why these events occur as well as their prevalence across different conditions unanswered.
OBJECTIVES: (1) To synthesize the evidence of prevalence of AEs in trial placebo groups across different conditions. (2) To compare AEs in trial placebo groups with AEs reported in untreated groups within a subset of randomized trials.
SEARCH METHODS: We searched PubMed for records with the word "nocebo" in the title and "systematic" in any field. We also contacted experts and hand-searched references of included studies.
STUDY ELIGIBILITY: We included any systematic review of randomized trials where nocebo effects were reported. We excluded systematic reviews of non-randomized studies.
PARTICIPANTS AND INTERVENTIONS: We included studies in any disease area.
STUDY APPRAISAL AND SYNTHESIS METHODS: We appraised the quality of the studies using a shortened version of the Assessment of Multiple Systematic Reviews tool (AMSTAR) tool. We reported medians and interquartile ranges (IQRs) of AEs. Among the trials within the review that included untreated groups, we compared the prevalence of AEs in untreated groups with the prevalence of AEs in placebo groups.
RESULTS: We identified 20 systematic reviews. These included 1271 randomized trials and 250,726 placebo-treated patients. The median prevalence of AEs in trial placebo groups was 49.1% (IQR 25.7-64.4%). The median rate of dropouts due to AEs was 5% (IQR 2.28-8.4%). Within the 15 of trials that reported AEs in untreated groups, we found that the AE rate in placebo groups (6.51%) was higher than that reported in untreated groups (4.25%).
LIMITATIONS: This study was limited by the quality of included reviews and the small number of trials that included untreated groups.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: AEs in trial placebo groups are common and cannot be attributed entirely to natural history. Trial methodologies that reduce AEs in placebo groups while satisfying the requirement of informed consent should be developed and implemented.

PMID: 30526685 [PubMed - indexed for MEDLINE]

A retrospective analysis of adverse events among patients receiving daptomycin versus vancomycin during outpatient parenteral antimicrobial therapy.

Infect Control Hosp Epidemiol. 2018 08;39(8):947-954

Authors: Schrank GM, Wright SB, Branch-Elliman W, LaSalvia MT

Abstract
OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) is a safe and effective alternative to prolonged inpatient stays for patients requiring long-term intravenous antimicrobials, but antimicrobial-associated adverse events remain a significant challenge. Thus, we sought to measure the association between choice of antimicrobial agent (vancomycin vs daptomycin) and incidence of adverse drug events (ADEs).
METHODS: Patients receiving OPAT treatment with vancomycin or daptomycin for skin and soft-tissue infections, bone and joint infections, endocarditis, and bacteremia or endovascular infections during the period from July 1, 2013, through September 30, 2016, were included. Demographic and clinical data were abstracted from the medical record. Logistic regression was used to compare ADEs requiring a change in or early discontinuation of therapy, hospital readmission, and emergency room visits between groups. Time from OPAT enrollment to ADE was compared using the log-rank test.
RESULTS: In total, 417 patients were included: 312 (74·8%) received vancomycin and 105 (25·2%) received daptomycin. After adjusting for age, Charlson comorbidity index, location of OPAT treatment, receipt of combination therapy with either β-lactam or fluoroquinolone, renal function, and availability of safety labs, patients receiving vancomycin had significantly higher incidence of ADEs (adjusted odds ratio [aOR], 3·71; 95% CI, 1·64-8·40). ADEs occurred later in the treatment course for patients treated with daptomycin (P<·01). Rates of readmission and emergency room visits were similar.
CONCLUSIONS: In the OPAT setting, vancomycin use was associated with higher incidence of ADEs than daptomycin use. This finding is an important policy consideration for programs aiming to optimize outcomes and minimize cost. Careful selection of gram-positive agents for prolonged treatment is necessary to limit toxicity.

PMID: 29893658 [PubMed - indexed for MEDLINE]

How to Consider Rare Genetic Variants in Personalized Drug Therapy.

Clin Pharmacol Ther. 2018 05;103(5):745-748

Authors: Lauschke VM, Ingelman-Sundberg M

Abstract
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME). In addition, genetic variation in factors encoding the major histocompatibility complex have been helpful to predict immune-mediated drug toxicity. This knowledge has been translated into clinical applications through the implementation of pharmacogenomic biomarkers. Over 230 of such markers that can, to a certain extent, predict drug efficacy or the likelihood of adverse drug reactions (ADRs) are recognized by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and are included in the drug labels of the respective medication. They are of particular value in cancer therapy to provide information of use to avoid ADRs and lack of response.

PMID: 29313952 [PubMed - indexed for MEDLINE]

Audit: Monitoring of side effects using GASS (Glasgow Antipsychotic Side-Effect Scale).

Psychiatr Danub. 2017 Sep;29(Suppl 3):685-686

Authors: Iankov B, Prabhakar S, Rahman A, Hosseini F

Abstract
BACKGROUND: Anti-psychotics are often prescribed off-licence for personality and affective disorders. The aim of this audit was to identify patients on specific wards within St Andrews Hospital and to determine how many of the Glasgow Antipsychotic Side-Effect Scale (GASS) forms had been completed as per policy.
METHODS: Thirteen patients of Dr Boris Iankov, Consultant Psychiatrist within the adolescent service at St Andrews, were identified. Their records were subsequently reviewed in order to determine how many had completed GASS forms.
RESULTS: It was found only 31% of patients had completed the GASS forms. The remaining patients were supported to do so. As a result 92% of patients are compliant with the policy.
RECOMMENDATIONS: The suitability of the form for adolescents was brought into question due to the sensitive nature of certain side effects. Furthermore the form should be completed routinely on admission and at regular intervals.

PMID: 28953853 [PubMed - indexed for MEDLINE]

Low body surface area predicts hepatotoxicity of nintedanib in patients with idiopathic pulmonary fibrosis.

Sci Rep. 2017 09 07;7(1):10811

Authors: Ikeda S, Sekine A, Baba T, Yamanaka Y, Sadoyama S, Yamakawa H, Oda T, Okuda R, Kitamura H, Okudela K, Iwasawa T, Ohashi K, Takemura T, Ogura T

Abstract
After the commercialization of nintedanib in Japan, a high incidence of hepatotoxicity resulting in treatment interruption was noted in idiopathic pulmonary fibrosis (IPF) patients treated with nintedanib in our hospital. This study aimed to clarify the risk factors for hepatotoxicity of nintedanib. Sixty-eight consecutive cases of IPF newly treated with nintedanib at a dose of 150 mg twice daily from September 2015 to September 2016 were enrolled: 46 patients (67.6%) exhibited aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) elevation and 16 patients (23.5%) also had a Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2. Body surface area (BSA) was significantly lower in the CTCAE grade ≥2 group than in another group. A multivariate logistic regression analysis showed that the association between BSA and AST/ALT elevation with CTCAE grade ≥2 was statistically significant. Eight of 10 patients who resumed nintedanib at a reduced dose of 100 mg twice daily after interruption due to hepatotoxicity did not again develop AST/ALT elevation. In conclusion, a low BSA was associated with hepatotoxicity of nintedanib at a dose of 150 mg twice daily. It would be a good option for patients with a small physique to start nintedanib at a dose of 100 mg twice daily and then increase if possible after confirming its safety.

PMID: 28883482 [PubMed - indexed for MEDLINE]

Increased Systemic Exposure and Stronger Cardiovascular and Metabolic Adverse Reactions to Fenoterol in Individuals with Heritable OCT1 Deficiency.

Clin Pharmacol Ther. 2018 05;103(5):868-878

Authors: Tzvetkov MV, Matthaei J, Pojar S, Faltraco F, Vogler S, Prukop T, Seitz T, Brockmöller J

Abstract
Fenoterol is a widely used anti-asthmatic and tocolytic agent, but high plasma concentrations of fenoterol may lead to severe and even fatal adverse reactions. We studied whether heritable deficiency of the liver organic cation transporter 1 (OCT1), a trait observed in 3% of Europeans and white Americans, affects fenoterol plasma concentrations and toxicity. OCT1 transported fenoterol with high affinity, and OCT1 inhibition in human hepatocytes reduced fenoterol uptake threefold. After administration of 180 µg of fenoterol to 39 healthy individuals, the OCT1-deficient individuals (zero active OCT1 alleles; n = 5) showed 1.9-fold greater systemic fenoterol exposure (P = 4.0 × 10-5 ) and 1.7-fold lower volume of distribution (P = 8.0 × 10-5 ). Correspondingly, the OCT1-deficient individuals had a 1.5-fold stronger increase in heart rate (P = 0.002), a 3.4-fold greater increase in blood glucose (P = 3.0 × 10-5 ), and significantly lower serum potassium levels. In conclusion, heritable OCT1 deficiency significantly increases plasma concentrations of fenoterol and may be an important factor underlying the excess mortality associated with fenoterol.

PMID: 28791698 [PubMed - indexed for MEDLINE]

Dexmedetomidine and sufentanil combination versus sufentanil alone for postoperative intravenous patient-controlled analgesia: a systematic review and meta-analysis of randomized controlled trials.

BMC Anesthesiol. 2019 May 18;19(1):81

Authors: Feng M, Chen X, Liu T, Zhang C, Wan L, Yao W

Abstract
BACKGROUND: Previous studies have demonstrated that dexmedetomidine improves the quality of postoperative analgesia. In the present study, we performed a meta-analysis of randomized controlled trials to quantify the effect of dexmedetomidine as an adjuvant to sufentanil for postoperative patient-controlled analgesia (PCA).
METHODS: PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched for randomized controlled trials in which dexmedetomidine was used as an adjuvant for PCA with sufentanil. In the retrieved studies, we quantitatively analyzed pain intensity, sufentanil consumption, and drug-related side effects.
RESULTS: Nine studies with 907 patients were included in this meta-analysis. Compared with sufentanil alone, dexmedetomidine-sufentanil for postoperative intravenous PCA reduced pain intensity at 24 h (mean difference (MD) = - 0.70points; 95% confidence interval (CI): - 1.01, - 0.39; P < 0.00001) and 48 h postoperatively (MD = -0.61points; 95% CI: - 1.00, - 0.22; P = 0.002). Moreover, dexmedetomidine-sufentanil reduced sufentanil consumption during the first 24 h (MD = -13.77 μg; 95% CI: - 18.56, - 8.97; P < 0.00001) and 48 h postoperatively (MD = -20.81 μg; 95% CI: - 28.20, - 13.42; P < 0.00001). Finally, dexmedetomidine-sufentanil improved patient satisfaction without increasing the incidence of side effects.
CONCLUSIONS: Dexmedetomidine as an adjuvant to sufentanil for postoperative PCA can reduce postoperative pain score and sufentanil consumption.

PMID: 31103031 [PubMed - in process]

Efficacy and safety of dulaglutide monotherapy compared with glimepiride in Chinese patients with type 2 diabetes: Post hoc analyses of a randomized, double-blind, phase 3 study.

J Diabetes Investig. 2019 May 18;:

Authors: Shi LX, Liu XM, Shi YQ, Li QM, Ma JH, Li YB, Du LY, Wang F, Chen LL

Abstract
AIMS/INTRODUCTION: To investigate the efficacy/safety of dulaglutide once-weekly monotherapy versus glimepiride in Chinese patients with type 2 diabetes.
MATERIALS AND METHODS: This was a post hoc analysis of a Chinese randomized, double-blind, noninferiority, phase 3 study. Patients (N=572) with inadequate glycemic control received dulaglutide 1.5 (n=189) or 0.75 (n=194) mg once-weekly or glimepiride (1 to 3 mg/day; n=189) for 26 weeks.
PRIMARY OBJECTIVE: noninferiority of dulaglutide 1.5 mg versus glimepiride for the change from baseline to Week 26 in glycated hemoglobin (HbA1c; noninferiority margin: 0.4%).
RESULTS: Dulaglutide 1.5 mg and 0.75 mg were noninferior (p<0.001) and superior (p≤0.002) versus glimepiride for the HbA1c change from baseline to Week 26. Least-squares mean differences (95% confidence interval) versus glimepiride: dulaglutide 1.5 mg, 0.53% (-0.74, -0.32); dulaglutide 0.75 mg, 0.32% ( 0.53, 0.12). Significantly more patients attained Week 26 HbA1c <7.0% in the dulaglutide 1.5 mg (71.7%) versus the glimepiride (57.5%; p=0.005) group. The decrease from baseline to Week 26 in fasting blood glucose was significantly more pronounced in both dulaglutide groups versus the glimepiride group (p<0.01). The overall incidence and rate of hypoglycemia were lower in both of the dulaglutide groups versus the glimepiride group. At Week 26, body weight had increased from baseline in the glimepiride group and decreased from baseline in both dulaglutide groups. The most frequent gastrointestinal drug related adverse events with dulaglutide were diarrhea, abdominal distension, nausea, and vomiting.
CONCLUSION: These findings support once-weekly dulaglutide monotherapy as a treatment for Chinese patients with early stage type 2 diabetes.ClinicalTrials. gov: NCT01644500. This article is protected by copyright. All rights reserved.

PMID: 31102326 [PubMed - as supplied by publisher]

Tiotropium add-on therapy is safe and reduces seasonal worsenings in paediatric asthma patients.

Eur Respir J. 2019 May 16;:

Authors: Vogelberg C, Szefler SJ, Vrijlandt EJLE, Boner AL, Engel M, Azzi GE, Vulcu SD, Moroni-Zentgraf PM, Eickmeier O, Hamelmann EH

Abstract
There remains an unmet need for effective, well tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance.Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 µg versus placebo add-on therapy in patients with symptomatic asthma aged 1-17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment.Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 µg (51%), 2.5 µg (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or gender. The number of AEs related to asthma symptoms and exacerbations was lower with tiotropium (5 µg) than with placebo, particularly during the seasonal peaks of these AEs.This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat® add-on therapy in paediatric patients with symptomatic asthma.Clinical Trial Registration: NinoTinA-asthma® (NCT01634113), CanoTinA-asthma® (NCT01634139), VivaTinA-asthma® (NCT01634152), RubaTinA-asthma® (NCT01257230), PensieTinA-asthma® (NCT01277523).

PMID: 31097514 [PubMed - as supplied by publisher]

Safety of nivolumab in metastatic renal cell carcinoma patients: A real-life experience in a Spanish urology setting.

Actas Urol Esp. 2019 May 13;:

Authors: Amores Bermúdez J, Osman García I, Unda Urzáiz M, Jiménez Marrero P, Ledo Cepero MJ, Llarena R, Flores Martín J, Abad Vivas-Pérez JI, Rodrigo Aliaga M, Juarez Soto A

Abstract
INTRODUCTION AND OBJECTIVES: Nivolumab is an immunotherapy agent that has been an approved treatment for previously treated patients with advanced renal cell carcinoma (RCC). Experience in real-life settings, especially regarding immune- related adverse events, is scarce. We present our experience with reference to the safety of nivolumab in patients with metastatic RCC (mRCC) treated in 9 hospitals in Spain.
MATERIAL AND METHODS: Retrospective, multicentre study of patients with mRCC treated with nivolumab between 2016 and 2018. Data on baseline socio-demographic and clinical characteristics and drug-related adverse events were collected.
RESULTS: The mean age of the 26 patients included was 63.7±11.5 years; 96% were ECOG 0-1 and 78% had favourable or intermediate MSKCC risk scores; 73% had the clear cell histological subtype and 30% metastatic disease. Median follow-up was 9 months (range 1-14). All patients experienced an adverse event at different grades, with fatigue, fever and anaemia being the most common (27%). Grade 3 adverse events occurred in 23% of patients. Adverse reactions led to treatment suspension in 3 patients (11%).
CONCLUSION: In the real-life clinical setting, nivolumab shows favourable outcomes, similar to those reported by other studies.

PMID: 31097211 [PubMed - as supplied by publisher]

Effectiveness of dienogest in improving quality of life in Asian women with endometriosis (ENVISIOeN): interim results from a prospective cohort study under real-life clinical practice.

BMC Womens Health. 2019 May 16;19(1):68

Authors: Techatraisak K, Hestiantoro A, Ruey S, Banal-Silao MJ, Kim MR, Seong SJ, Thaufik S, Ahlers C, Shin SY, Lee BS

Abstract
BACKGROUND: Dienogest has been shown to substantially improve endometriosis-associated symptoms such as debilitating chronic pelvic pain, and in turn, health-related quality of life (HRQoL). To date, there is no data on patient-reported outcomes reflecting the real-world practice in Asia where endometriosis is a relevant health, social and economic burden. This non-interventional, multi-center, prospective study aims to investigate the influence of dienogest on HRQoL.
METHODS: Asian women received dienogest (2 mg/daily) and were followed for 24 months. The effectiveness of dienogest to improve HRQoL and endometriosis-associated pelvic pain (EAPP) was assessed by patient-reported outcomes. HRQoL, especially the "pain" domain as primary endpoint, was evaluated with the Endometriosis Health Profile-30 (EHP-30) questionnaire. The numeric rating scale served to determine changes in the severity of EAPP. Within the presented interim analysis (data cut-off: 2017-11-27), the mean changes in EHP-30 and EAPP scores from baseline to 6 months upon availability of the data were evaluated. Treatment-emergent adverse events (TEAEs) and bleeding profiles were documented.
RESULTS: Dienogest therapy decreased EHP-30 scores in all assessed domains (score 0-100, lower scores indicate better HRQoL). Primarily, the "pain" domain was improved in 78.4% of patients. EAPP was reduced (score 0-10, lower scores reflect less pain), highlighted by a mean reduction of the pain score by - 4.5 points. Patients with a higher EAPP score at baseline had an increased response to dienogest (- 6.2 points mean change) compared to patients with low baseline EAPP severity (- 1.4 points mean change). Both surgically and clinically diagnosed patients described comparable pain reduction, as well as women with or without prior treatment. Drug-related TEAEs were documented for 31.5% of patients, with amenorrhoea (5.9%) and metrorrhagia (5.1%) being the most common events. The bleeding pattern was changed upon dienogest, characterized by decreased normal bleeding (84.2 to 28.8%) and increased amenorrhea (3.2 to 42.9%) at 6 months.
CONCLUSION: The data indicate an amelioration of HRQoL and EAPP upon dienogest therapy. No new safety signals were observed. Therefore, its use as first-line therapy for long-term management of debilitating and chronic endometriosis-associated pain represents an interesting option that remains to be further investigated.
TRIAL REGISTRATION: Name of registry: Clinical Trials Clinicaltrials.gov registration number: NCT02425462 Registration date: 2015-04-24. Registration timing: prospective.

PMID: 31096979 [PubMed - in process]

Impact of Pharmacist-led Home Medicines Review Services on Drug-Related Problems Among Elderly Population: A Systematic Review.

Epidemiol Health. 2019 May 17;:e2019020

Authors: Gudi SK, Kashyap A, Chhabra M, Muhammed R, Tiwari KK

Abstract
Objectives: To address and elucidate the impact of pharmacist-led Home Medicines Review (HMR) in identifying various drug-related problems (DRPs) among the elderly population in homecare settings.
Methods: A comprehensive systematic search was performed using the scientific electronic databases like PubMed, Scopus, Embase, and Web of Science for the studies published between 1 January 2008 to 31 December 2018 pertaining to HMR services by the pharmacist in identifying drug-related problems.
Results: In total, 4292 studies were retrieved from the searches; and of these, 24 were excluded as they were duplicates. Titles and abstracts were screened for the remaining 4268 studies; and of them, 4239 articles were excluded due to the extraneous nature of the titles and/or abstracts. Subsequently, 29 full-text articles were assessed, and 19 were removed for lacking the outcome of interest and/or not satisfying the study's inclusion criteria. At last, ten studies were included in the review. The pharmacist identified a highly significant count of DRPs through HMR services across all the studies. Of them, the most common type of DRPs were, potential drug-drug interactions, serious adverse drug reactions, need for an additional drug, inappropriate medication use, non-adherence, untreated indication, overdose, and usage of expired medications.
Conclusion: HMR is a novel and extended role of the pharmacist, which is efficient in identifying and resolving the DRPs which could eventually minimize the patient's health-related cost & burden, and thus enhance the quality of life and well-being among the elderly.

PMID: 31096747 [PubMed - as supplied by publisher]

Semi-Supervised Recurrent Neural Network for Adverse Drug Reaction mention extraction.

BMC Bioinformatics. 2018 06 13;19(Suppl 8):212

Authors: Gupta S, Pawar S, Ramrakhiyani N, Palshikar GK, Varma V

Abstract
BACKGROUND: Social media is a useful platform to share health-related information due to its vast reach. This makes it a good candidate for public-health monitoring tasks, specifically for pharmacovigilance. We study the problem of extraction of Adverse-Drug-Reaction (ADR) mentions from social media, particularly from Twitter. Medical information extraction from social media is challenging, mainly due to short and highly informal nature of text, as compared to more technical and formal medical reports.
METHODS: Current methods in ADR mention extraction rely on supervised learning methods, which suffer from labeled data scarcity problem. The state-of-the-art method uses deep neural networks, specifically a class of Recurrent Neural Network (RNN) which is Long-Short-Term-Memory network (LSTM). Deep neural networks, due to their large number of free parameters rely heavily on large annotated corpora for learning the end task. But in the real-world, it is hard to get large labeled data, mainly due to the heavy cost associated with the manual annotation.
RESULTS: To this end, we propose a novel semi-supervised learning based RNN model, which can leverage unlabeled data also present in abundance on social media. Through experiments we demonstrate the effectiveness of our method, achieving state-of-the-art performance in ADR mention extraction.
CONCLUSION: In this study, we tackle the problem of labeled data scarcity for Adverse Drug Reaction mention extraction from social media and propose a novel semi-supervised learning based method which can leverage large unlabeled corpus available in abundance on the web. Through empirical study, we demonstrate that our proposed method outperforms fully supervised learning based baseline which relies on large manually annotated corpus for a good performance.

PMID: 29897321 [PubMed - indexed for MEDLINE]

[A CASE OF RENAL CELL CARCINOMA WITH INFERIOR VENA CAVAL TUMOR THROMBUS WHICH THE REDUCTION OF TUMOR IN SPITE OF DRUG DISCONTINUANCE AFTER THE FULMINANT HEPATITIS ONSET WITH THE SUNITNIB].

Nihon Hinyokika Gakkai Zasshi. 2018;109(2):102-105

Authors: Shichijo T, Koizumi S, Ogawa Y, Matsubara E, Matsumoto Y, Saito K, Inoue K, Ogawa Y, Samejima M, Odagane T, Ishihara M, Higaki Y

Abstract
A 70-year-old man presented with right renal cell carcinoma with inferior vena caval tumor thrombus into the right atrium. CT Scan presented local invasion and lymph node metastasis. We estimated inoperative case, so he was started sunitinib. After 5 month he had general fatigue and admitted to our hospital. He diagnosed serious adverse events of fulminant hepatitis and left ventricular systolic dysfunction and discontinued sunitnib. After drug discontinuance reduction of tumor and tumor thrombus were detected. 7-months later, we showed the increase of tumor and the improvement of the left ventricular systolic dysfunction. We performed right renal nephrectomy and it passes now in 14 months after surgery, but doses not show a recurrence, metastasis.

PMID: 31006738 [PubMed - indexed for MEDLINE]

The efficacy comparison of carvedilol plus endoscopic variceal ligation and traditional, nonselective β-blockers plus endoscopic variceal ligation in cirrhosis patients for the prevention of variceal rebleeding: a meta-analysis.

Eur J Gastroenterol Hepatol. 2019 May 14;:

Authors: Yang J, Ge K, Chen L, Yang JL

Abstract
BACKGROUND: Currently, the first-line treatment regimen in cirrhotic patients for variceal rebleeding prophylaxis is still under debate.
AIM: This study aimed to compare the efficacy and safety of carvedilol plus endoscopic variceal ligation (EVL) and traditional, nonselective β-blockers (NSBBs) plus EVL in preventing variceal rebleeding.
PATIENTS AND METHODS: Studies were found in PubMed, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Med Online, and Wiper Database. Review Manager 5.3 was used to analyze the relevant data.
RESULTS: Nine trials including 802 patients were identified (402 for carvedilol and 400 for traditional NSBBs). Carvedilol was more efficacious than traditional NSBBs in decreasing the variceal rebleeding rate [odds ratio (OR): 0.53; 95% confidence interval (CI): 0.38-0.75; P=0.0003], lowering the degree of esophageal varices (OR: 4.40; 95% CI: 2.64-7.34; P<0.00001), decreasing the mean arterial pressure (standard mean difference: -0.35; 95% CI: -0.56 to -0.14; P=0.0009), reducing the total adverse events occurrence (OR: 0.39; 95% CI: 0.28-0.53; P<0.00001), and decreasing drug-related adverse events (OR: 0.37; 95% CI: 0.25-0.56; P<0.00001). No difference was noted between carvedilol and traditional NSBBs with respect to mortality and heart rate (OR: 0.72; 95% CI: 0.43; 1.22; P=0.22 and standard mean difference: 0.09; 95% CI: -0.12 to 0.30; P=0.40, respectively).
CONCLUSION: Combined with variceal ligation, carvedilol was more effective and safer than traditional NSBBs in the prevention of rebleeding in cirrhotic patients.

PMID: 31094853 [PubMed - as supplied by publisher]

Drug-induced interstitial lung disease: role of pharmacogenetics in predicting cytotoxic mechanisms and risks of side effects.

Curr Opin Pulm Med. 2019 May 06;:

Authors: Jessurun NT, Drent M, van Puijenbroek EP, Bekers O, Wijnen PA, Bast A

Abstract
PURPOSE OF REVIEW: The diagnosis of drug-induced interstitial lung disease (DI-ILD) is challenging and mainly made by exclusion of other possible causes. Toxicity can occur as a cause of drug(s) or drug-drug interactions. In this review, we summarize the possible role of pharmacogenetics of metabolizing enzymes in DI-ILD.
RECENT FINDINGS: Knowledge of the genetic predispositions of enzymes involved in drug metabolization and their relation with proposed cytotoxic mechanisms of DI-ILD, in particular direct cell toxicity and free oxygen radical production is increasing. The cytochrome P450 enzyme family and other enzymes play an important role in the metabolism of all sorts of ingested, injected, or inhaled xenobiotic substances. The liver is the major site for metabolism. Metabolic cytotoxic mechanisms have however also been detected in lung tissue. Polymorphisms in genes coding for enzymes that influence metabolic activity may lead to localized (toxic) reactions and tissue damage. This knowledge may be helpful in preventing the risk of DI-ILD.
SUMMARY: Drug toxicity can be the consequence of absence or very poor enzyme activity, especially if no other metabolic route is available. In the case of reduced enzyme activity, it is recommended to reduce the dose or to prescribe an alternative drug, which is metabolized by a different, unaffected enzyme system to prevent toxic side effects. However, enhanced enzyme activity may lead to excessive formation of toxic and sometimes reactive metabolites. Therefore, knowing a patient's drug-metabolizing profile before drug prescription is a promising way to prevent or explain DI-ILD.

PMID: 31094717 [PubMed - as supplied by publisher]

Yellow fever vaccine and risk of developing serious adverse events: a systematic review.

Rev Panam Salud Publica. 2018;42:e75

Authors: Porudominsky R, Gotuzzo EH

Abstract
Objective: To evaluate contraindications and precautions for the yellow fever vaccine (YFV) in risk populations.
Methods: A literature review was conducted by searching PubMed for "yellow fever vaccine" and "adverse events" (AEs); 207 studies were found, and 43 of them met the inclusion criteria and were included in a systematic review.
Results: The results for first dose of YFV in elderly patients were conflicting-some showed AEs while some showed benefits. Therefore, precaution and case-by-case decisionmaking for YFV in this population are advised. The same precautions are warranted for YFV in infants 6-8 months, with the vaccine contraindicated in those < 6 months old and safe after 9 months of age. YFV seems safe in the first trimester of pregnancy, and probably throughout gestation, as it was not associated with increased malformations. During breastfeeding, YFV continues to be controversial. The vaccine seems safe in people being treated with immunomodulatory or immunosuppressive therapy, people with immunosuppressive diseases, and solid organ and hematopoietic stem cell transplant patients; in stem cell transplants, however, a booster dose should only be applied once immunity is recovered. HlV-infected patients with a CD4+ count > 200 cells/mm3 do not have increased risk of AEs from YFV. Egg allergy vaccination protocols seem to provide a safe way to immunize these patients.
Conclusions: YFV safety has been confirmed based on data from many vaccination campaigns and multiple studies. AEs seem more frequent after a first-time dose, mainly in risk groups, but this review evaluated YFV in several of the same risk groups and the vaccine was found to be safe in most of them.

PMID: 31093103 [PubMed]

Reporting of adverse reactions to benznidazole: does medical expertise matter?

Rev Panam Salud Publica. 2018;42:e69

Authors: Pereiro AC, Lenardón M, Zeballos A, Chopita M, Abril M, Gold S

Abstract
This study evaluated and compared follow-up and adverse drug reaction (ADR) reporting for Chagas disease (CD) patients treated with benznidazole (BZN) by two health teams with different levels of experience, using medical records for 204 patients participating in the first year of a scaled-up public health program for CD case detection and treatment conducted at all 46 primary health care centers in La Plata district, Buenos Aires, Argentina, in 2014. Both teams were experienced in CD patient management and trained in BZN administration, and included senior physicians, but one team had no experience in administering BZN while the other team had three years of experience due to their participation in the program's pilot project. Patients with positive serology for CD were treated with 5 mg/kg/day of BZN for 60 days. Patients' median age was 35 years and 84.3% were female. There was a statistically significant difference in the number of ADRs reported by the experienced versus the inexperienced health teams (18 versus 44 respectively; P < 0.001). Health team experience in administering BZN to CD patients, and treatment duration, were significantly associated with reporting of ADRs (adjusted odds ratios (aORs) 0.340 (95% confidence interval (CI): 0.177-0.652) and 0.967 (CI: 0.942-0.993) respectively). ADR reporting increased with patient age, occurring at the highest frequency (42.9%) in people 50+ years old. All treatment discontinuations (nine) occurred in patients followed up by the inexperienced health team. Level of experience in BZN administration to CD patients was significantly and inversely associated with frequency of ADR reports: inexperienced health team members tended to report more.

PMID: 31093097 [PubMed]

The role of pharmacogenomics in adverse drug reactions.

Expert Rev Clin Pharmacol. 2019 May;12(5):407-442

Authors: Cacabelos R, Cacabelos N, Carril JC

Abstract
INTRODUCTION: Adverse drug reactions (ADRs) are a major health concern worldwide. There are multiple causes of ADRs, some of which are preventable. Pharmacogenomics accounts for ≈80% variability in drug efficacy and safety. Over 400 genes are clinically relevant in drug metabolism, and ≈200 pharmagenes are associated with ADRs. The condition of extensive metabolizer in the Caucasian population is lower than 20%, and about 60% of patients are exposed to potential ADRs. Areas covered: Important topics related to pharmacogenomics in drug efficacy and safety are covered, including: (i) major components of the pharmacogenomic machinery; (ii) epigenetic regulation of pharmagene expression; and (iii) pharmacogenomics-related ADRs of different drug categories. Expert opinion: The Regulatory Agencies should make recommendations to the pharmaceutical industry in favor of the introduction of pharmacogenomics in drug development and the inclusion of pharmacogenomic information on drug labels, with specific warnings for the population at risk. Educational programs are fundamental for drug prescribers to become familiar with personalized treatments. Pharmacogenetic testing should be gradually introduced into medical practice. ADRs can be reduced not only by adherence to prescribing guidelines, suitable monitoring and regular medication review, but also by the implementation of pharmacogenomic procedures in the clinical setting.

PMID: 30916581 [PubMed - indexed for MEDLINE]