Modeling polypharmacy side effects with graph convolutional networks.

Bioinformatics. 2018 07 01;34(13):i457-i466

Authors: Zitnik M, Agrawal M, Leskovec J

Abstract
Motivation: The use of drug combinations, termed polypharmacy, is common to treat patients with complex diseases or co-existing conditions. However, a major consequence of polypharmacy is a much higher risk of adverse side effects for the patient. Polypharmacy side effects emerge because of drug-drug interactions, in which activity of one drug may change, favorably or unfavorably, if taken with another drug. The knowledge of drug interactions is often limited because these complex relationships are rare, and are usually not observed in relatively small clinical testing. Discovering polypharmacy side effects thus remains an important challenge with significant implications for patient mortality and morbidity.
Results: Here, we present Decagon, an approach for modeling polypharmacy side effects. The approach constructs a multimodal graph of protein-protein interactions, drug-protein target interactions and the polypharmacy side effects, which are represented as drug-drug interactions, where each side effect is an edge of a different type. Decagon is developed specifically to handle such multimodal graphs with a large number of edge types. Our approach develops a new graph convolutional neural network for multirelational link prediction in multimodal networks. Unlike approaches limited to predicting simple drug-drug interaction values, Decagon can predict the exact side effect, if any, through which a given drug combination manifests clinically. Decagon accurately predicts polypharmacy side effects, outperforming baselines by up to 69%. We find that it automatically learns representations of side effects indicative of co-occurrence of polypharmacy in patients. Furthermore, Decagon models particularly well polypharmacy side effects that have a strong molecular basis, while on predominantly non-molecular side effects, it achieves good performance because of effective sharing of model parameters across edge types. Decagon opens up opportunities to use large pharmacogenomic and patient population data to flag and prioritize polypharmacy side effects for follow-up analysis via formal pharmacological studies.
Availability and implementation: Source code and preprocessed datasets are at: http://snap.stanford.edu/decagon.

PMID: 29949996 [PubMed - indexed for MEDLINE]

Regorafenib-Induced Hand-Foot Skin Reaction Is More Severe on the Feet Than on the Hands.

Oncol Res. 2019 May 07;27(5):551-556

Authors: Nonomiya Y, Yokokawa T, Kawakami K, Kobayashi K, Aoyama T, Takiguchi T, Sugisaki T, Suzuki K, Suenaga M, Wakatsuki T, Yamaguchi K, Sugimoto Y, Hama T

Abstract
Regorafenib is a multikinase inhibitor for the treatment of metastatic colorectal cancer. Regorafenib-induced hand-foot skin reaction (HFSR) is a common side effect during treatment. The reported frequency of HFSR was 80% (grade 3: 28%) in the Japanese subpopulation in the CORRECT trial; however, more detailed data regarding HFSR in terms of onset and sites of susceptibility are unclear. Additionally, the risk factors for regorafenib-induced severe HFSR are unknown. The aim of this study was to compare HFSR between the hands and feet and identify preexisting risk factors for severe HFSR in Japanese patients receiving regorafenib. We retrospectively examined the onset and severity of HFSR on the hands and feet of patients with metastatic colorectal cancer treated with regorafenib from May 2013 to October 2015 in the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. In addition, we examined the possible association between preexisting clinical factors and severe HFSR. Our results showed that no significant difference in the incidence of HFSR of any grade was observed between the hands (71%) and feet (74%) (p = 0.63). The incidence of grade 3 HFSR was more frequent on the feet (33%) than on the hands (8%) (p < 0.01). The onset of grade 3 HFSR was earlier on the feet than on the hands (p < 0.001). No preexisting risk factor was identified. Our findings indicate that severe HFSR was more prevalent on the feet than on the hands, suggesting the need for appropriate screening for early detection and treatment of regorafenib-induced HSFR.

PMID: 29914591 [PubMed - indexed for MEDLINE]

Is ticagrelor worth its high cost and side-effects?

Acta Cardiol. 2019 Apr;74(2):93-98

Authors: Guerbaai RA, Mahata I, Maréchaux S, Le Jemtel TH, Ennezat PV

Abstract
Ticagrelor is a reversible P2Y12 receptor antagonist that is more potent than clopidogrel. When used in combination with aspirin, it reduces cardiovascular events in patients with acute coronary syndrome. However, unbiased review of 5 randomised controlled trials indicates that although statistically significant, the clinical superiority of ticagrelor over clopidogrel is modest. Thus, identification of patients who benefit the most from ticagrelor is a priority. Besides bleeding issues, ticagrelor can frequently cause bouts of dyspnoea, which requires ticagrelor replacement by another P2Y12 receptor antagonist, with a loading dose.

PMID: 29730968 [PubMed - indexed for MEDLINE]

Prediction of individual outcomes for asthma sufferers.

Biostatistics. 2018 10 01;19(4):579-593

Authors: Storlie CB, Branda ME, Gionfriddo MR, Shah ND, Rank MA

Abstract
We consider the problem of individual-specific medication level recommendation (initiation, removal, increase, or decrease) for asthma sufferers. Asthma is one of the most common chronic diseases in both adults and children, affecting 8% of the US population and costing $37-63 billion/year in the United States of America. Asthma is a complex disease, whose symptoms may wax and wane, making it difficult for clinicians to predict outcomes and prognosis. Improved ability to predict prognosis can inform decision making and may promote conversations between clinician and provider around optimizing medication therapy. Data from the US Medical Expenditure Panel Survey (MEPS) years 2000-2010 were used to fit a longitudinal model for a multivariate response of adverse events (Emergency Department or in-patient visits, excessive rescue inhaler use, and oral steroid use). To reduce bias in the estimation of medication effects, medication level was treated as a latent process which was restricted to be consistent with prescription refill data. This approach is demonstrated to be effective in the MEPS cohort via predictions on a validation hold out set and a synthetic data simulation study. This framework can be easily generalized to medication decisions for other conditions as well.

PMID: 29121247 [PubMed - indexed for MEDLINE]

14 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 2019/08/27

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.

Prognostic Impact and Risk Factors of Immune-Related Pneumonitis in Patients With Non-Small-Cell Lung Cancer Who Received Programmed Death 1 Inhibitors.

Clin Lung Cancer. 2019 Aug 01;:

Authors: Fukihara J, Sakamoto K, Koyama J, Ito T, Iwano S, Morise M, Ogawa M, Kondoh Y, Kimura T, Hashimoto N, Hasegawa Y

Abstract
INTRODUCTION: Pneumonitis is one of the immune-related adverse events of programmed death 1 (PD-1) inhibitors that sometimes cause lethal outcomes. Although some recent reports have described PD-1 inhibitors as more effective in non-small-cell lung cancer (NSCLC) patients with immune-related adverse events than in those without, few data are available on the prognosis of those treated with PD-1 inhibitors who developed immune-related pneumonitis (IRP). Additionally, the robust risk factors of IRP have not been well elucidated.
PATIENTS AND METHODS: A retrospective review of patients with recurrent or advanced NSCLC who took a PD-1 inhibitor (nivolumab or pembrolizumab monotherapy) between January 2016 and March 2018 was undertaken. Radiologic findings such as unilateral infiltration were also defined as IRP as long as they were deemed relevant to PD-1 inhibitors.
RESULTS: Twenty-seven (16%) of 170 patients developed IRP. Although 22 (81%) of 27 patients with IRP recovered with drug cessation with or without corticosteroid therapy, 8-week landmark analysis showed the overall survival after administration of the PD-1 inhibitor was significantly shorter in patients with IRP than in those without (8.7 vs. 23.0 months, P = .015). Patients with IRP tended to not receive next-line treatment and choose best supportive care after cessation of PD-1 inhibitor therapy. In the multivariate analysis, pembrolizumab (vs. nivolumab) and low serum albumin were independent risk factors for IRP.
CONCLUSION: Development of IRP was correlated with poor prognosis in patients with NSCLC. Further study is necessary for establishing the best prediction and management strategies for IRP.

PMID: 31446020 [PubMed - as supplied by publisher]

[Proarrhythmic adverse effects of nonarrhythmic drugs].

Herzschrittmacherther Elektrophysiol. 2019 Aug 23;:

Authors: Jungbauer CG, Maier LS

Abstract
Acquired QT prolongation is almost exclusively the result of inhibition of the potassium channel Ikr. Especially hospitalized patients have a high risk to suffer from Torsade de points (TdP). Therefore, any prescription of drugs with the potential for QT prolongation should involve the consideration of the necessity of the agent and interaction with other QT prolonging drugs. The website www.crediblemed.com helps to identify the risk for TdP of each drug. During drug prescription, it is necessary to monitor QTc with regular ECGs; QTc prolongation >500 ms or QTc increase >60 ms should trigger end of drug administration followed by monitoring of the patient according to the individual risk for TdP.

PMID: 31444571 [PubMed - as supplied by publisher]

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 2019/08/24

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.

15 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 2019/08/24

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.

Efficacy and safety of PD-1 inhibitors for treating advanced melanoma: a systematic review and meta-analysis.

Immunotherapy. 2018 11;10(15):1293-1302

Authors: Li J, Gu J

Abstract
AIM: We conducted a meta-analysis to systematically review the efficacy and safety of programmed cell death 1 (PD-1) inhibitors for advanced melanoma.
STUDY DESIGN: The relevant studies of the randomized controlled trials in melanoma patients treated with PD-1 inhibitors were retrieved and the systematic evaluation was conducted. Databases were searched till June 2018.
RESULTS: PD-1 inhibitors significantly improved the progression-free survival, overall survival and overall response rate in patients with advanced melanoma. Progression-free survival, overall survival and overall response rate did not vary significantly according to PD-L1 status, V-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations and type of drug, but varied significantly by control therapy. PD-1 inhibitors were associated with a decreased risk of adverse events compared with ipilimumab, but an increased risk of immune-related events compared with chemotherapy.
CONCLUSION: The PD-1 inhibitors-containing therapy was efficacious in treating advanced melanoma.

PMID: 30474476 [PubMed - indexed for MEDLINE]

Risk of fatigue in cancer patients treated with anti programmed cell death-1/anti programmed cell death ligand-1 agents: a systematic review and meta-analysis.

Immunotherapy. 2018 11;10(15):1303-1313

Authors: Santoni M, Conti A, Buti S, Bersanelli M, Foghini L, Piva F, Giulietti M, Lusuardi L, Battelli N

Abstract
AIM: We aimed to assess the incidence and relative risk (RR) of fatigue in cancer patients treated with anti programmed cell death-1 (PD-1) and anti programmed cell death ligand-1 (PD-L1) agents.
PATIENTS & METHODS: Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Incidence, RR and 95% CIs were calculated using random or fixed-effects models.
RESULTS: Thirty-eight studies were included in this analysis, with a total of 11,719 patients. The incidences were 23.4 and 2.1% for all- and high-grade fatigue, respectively. The highest incidence of high-grade fatigue was reported by the combination of nivolumab and ipilimumab. Overall RR of high-grade fatigue with anti-PD-1/PD-L1 compared with chemotherapy or targeted therapy was 0.48.
CONCLUSION: Treatment with anti-PD-1/PD-L1 agents correlates with lower incidence and RR of fatigue compared with standard therapies.

PMID: 30474475 [PubMed - indexed for MEDLINE]

Nutrition impact symptoms and associated outcomes in post-chemoradiotherapy head and neck cancer survivors: a systematic review.

J Cancer Surviv. 2018 08;12(4):479-494

Authors: Crowder SL, Douglas KG, Yanina Pepino M, Sarma KP, Arthur AE

Abstract
PURPOSE: It is estimated that more than 90% of head and neck cancer (HNC) survivors who underwent chemoradiotherapy experience one or more nutrition impact symptoms (NIS) in the months or years thereafter. Despite the high prevalence, there is limited research addressing long-term impact of NIS on outcomes such as nutrition and quality of life in HNC survivors treated with chemoradiotherapy.
OBJECTIVE: To conduct a systematic review of the literature pertaining to the presence of nutrition impact symptoms and their associated outcomes in post-chemoradiotherapy head and neck cancer survivors.
EVIDENCE REVIEW: A systematic review was conducted across three databases according to PRISMA guidelines and used to identify current literature regarding NIS in HNC survivors. A keyword search was conducted in PubMed, Scopus, and Web of Science from 2007 to 2017. Studies that met all of the following criteria were included in the review: (1) studies must include human subjects with a HNC diagnosis; (2) study participants must have received chemoradiotherapy; (3) study participants must have been post-treatment for a minimum of 3 months at the time of data collection; (4) full-text articles must have appeared in peer-reviewed journals; (5) papers must have been published in English; (6) studies must be quantitative in nature; (7) studies must have reported at least one NIS; and (8) studies must address at least one of the following outcomes: nutrition, functional status, or quality of life. Two independent reviewers assessed study quality using a predefined set of criteria.
FINDINGS: A systematic search yielded 1119 papers, of which 15 met the inclusion criteria. The study reviewed existing evidence of NIS in a variety of HNC survivors ranging from 3 months to greater than 10 years post-chemoradiotherapy treatment. Eight hundred forty-nine study participants were included in the review. Of the 15 studies, 10 were designed as prospective cohort studies, 4 were cross-sectional studies, and 1 was a retrospective cohort study. Functional impairments as a result of chemoradiotherapy to the head and neck are prevalent in research and include dysphagia, xerostomia, trismus, salivary issues, mucositis, and oral pain.
CONCLUSIONS: NIS negatively influence HNC survivors beyond the acute phase of treatment. These symptoms are associated with decreased nutrition and quality of life. Interventions are necessary to improve survivors' eating challenges beyond the completion of treatment. If practitioners do not follow patients long term, patients may suffer consequences of NIS including malnutrition risk, weight loss, and decreased food intake and quality of life.
IMPLICATIONS FOR CANCER SURVIVORS: The prevalence and consequences of nutrition impact symptoms are substantial among head and neck cancer survivors beyond the acute phase of cancer treatment. Oncology clinicians should continuously monitor and manage these symptoms throughout the cancer continuum.

PMID: 29556926 [PubMed - indexed for MEDLINE]

Use of a web-based app to improve breast cancer symptom management and adherence for aromatase inhibitors: a randomized controlled feasibility trial.

J Cancer Surviv. 2018 08;12(4):431-440

Authors: Graetz I, McKillop CN, Stepanski E, Vidal GA, Anderson JN, Schwartzberg LS

Abstract
PURPOSE: For postmenopausal women with hormone receptor-positive breast cancer, long-term use of aromatase inhibitors (AIs) significantly reduces the risk of cancer recurrence and improves survival. Still, many patients are nonadherent due to adverse side effects. We conducted a pilot randomized controlled trial to test the use of a web-based application (app) designed with and without weekly reminders for patients to report real-time symptoms and AI use outside of clinic visits with built-in alerts to patients' oncology providers. Our goal was to improve symptom burden and medication adherence.
METHODS: Forty-four women with early-stage breast cancer and a new AI prescription were randomized to either an App+Reminder (weekly reminders to use app) or an App (no reminders) group. Pre- and post-assessment data were collected from all participants.
RESULTS: Participants in the App+Reminder group had higher weekly app usage rate (74 vs. 38%, p < 0.05) during the intervention and reported higher AI adherence at 8 weeks (100 vs. 72%, p < 0.05). Symptom burden increase was higher for the App group compared to the App+Reminder group but did not reach statistical significance.
CONCLUSIONS: Weekly reminders to use a web-based app to report AI adherence and treatment-related symptoms demonstrated feasibility and improved short-term AI adherence, which may reduce symptom burden for women with breast cancer and a new AI prescription.
IMPLICATIONS FOR CANCER SURVIVORS: If short-term gains in adherence persist, this low-cost intervention could improve survival outcomes for women with breast cancer. A larger, long-term study should examine if AI adherence and symptom burden improvements persist for a 5-year treatment period.

PMID: 29492753 [PubMed - indexed for MEDLINE]

Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial.

AIDS Res Hum Retroviruses. 2018 02;34(2):193-205

Authors: Viegas EO, Tembe N, Nilsson C, Meggi B, Maueia C, Augusto O, Stout R, Scarlatti G, Ferrari G, Earl PL, Wahren B, Andersson S, Robb ML, Osman N, Biberfeld G, Jani I, Sandström E

Abstract
We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10; 2 × 0.1 ml) or 1,200 μg (n = 10; 2 × 0.2 ml) of HIV-DNA (3 mg/ml), followed by two boosts of 108 pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Envelope (Env). After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher dose group (median 420 vs. 157.5 SFC/million peripheral blood mononuclear cell, p = .014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 ml using Zetajet was safe and well tolerated. Priming with the 1,200 μg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.

PMID: 28969431 [PubMed - indexed for MEDLINE]

[Information on the risk of drugs in pregnancy: New regulation of the Food and Drug Administration].

Aten Primaria. 2017 12;49(10):622-623

Authors: García Caeiro ÁL, Rey Liste MT, Ventosa Rial JJ, Alonso Fachado A

PMID: 28844480 [PubMed - indexed for MEDLINE]

[ANTIBIOTIC PRESCRIPTION ERRORS IN PATIENTS HOSPITALIZED IN INTERNAL MEDICINE DEPARTMENTS - A PROSPECTIVE COHORT STUDY].

Harefuah. 2019 May;158(5):294-298

Authors: Zayyad H, Yashar H, Kurnik D, Paul M

Abstract
AIMS: To examine the prevalence of antibiotic prescription errors in three medical departments.
BACKGROUND: Prescription errors are common and associated with significant adverse drug events (ADEs), morbidity and mortality, and health care expenditures.
METHODS: A prospective observational cohort study was conducted in three medical departments, including consecutive patients with suspected or proven infections, and/or antibiotic prescriptions. The primary outcome was the proportion of prescription errors, defined as: contraindications, inadequate dose regimen, and unnecessary antibiotic treatment. Secondary outcomes included incidence of ADEs, proportion of potential drug-drug interactions (DDIs) with clinical relevance, and prevalence of inadequate monitoring for ADEs and therapeutic drug monitoring (TDM).
RESULTS: We identified 327 patient-episodes in 295 patients. The most common infectious diagnoses were urinary tract infection and pneumonia. Among 633 prescriptions, 113 (18%) contained errors in 87 (27%) patient-episodes. The most common types of error were inappropriate dose adjustment for renal function and unnecessary treatment. There were 6 prescriptions with contraindications (0.9%). Laboratory monitoring was required in 259 patient-episodes but inadequate in 40 (15%). TDM was required in 40 patient-episodes, but was not performed in 25 (63%). There were 69 ADEs in 61 patient-episodes (19%). Compared to patients without ADEs, patients who developed ADEs had more prescription errors (p=0.055), more potential DDIs (p=0.012), and received more often antibiotics that needed monitoring and TDM.
CONCLUSIONS: Antibiotic prescription errors in medical departments are common and may be associated with significant ADEs. Our findings may help in prioritizing the customization of prescription computer decision support systems to improve antibiotic prescription.

PMID: 31104388 [PubMed - indexed for MEDLINE]

Effectiveness of the probiotic Streptococcus salivarius K12 for the treatment and/or prevention of sore throat: a systematic review.

Clin Microbiol Infect. 2019 Jun;25(6):673-680

Authors: Wilcox CR, Stuart B, Leaver H, Lown M, Willcox M, Moore M, Little P

Abstract
BACKGROUND: Sore throat resulting from pharyngotonsillitis is one of the commonest reasons for primary care consultation and inappropriate antibiotic prescription and finding effective alternative treatments is important.
OBJECTIVES: To review the evidence for using the probiotic Streptococcus salivarius K12 (SsK12) for the prevention or treatment of pharyngotonsillitis.
DATA SOURCES: PubMed, Embase, CINAHL and Cochrane Library.
STUDY ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs).
PARTICIPANTS: Adults or children.
INTERVENTIONS: SsK12 as active treatment or prophylaxis, against pharyngotonsillitis.
METHODS: Literature search.
RESULTS: Four articles were identified (1846 participants). All were deemed to be of poor quality using the Cochrane risk-of-bias assessment. Two trials studied SsK12 prophylaxis for streptococcal pharyngitis (children without history of recurrence). One compared daily administration of SsK12 to no treatment over 6 months (n = 222, age 33-45 months), reporting significantly lower incidence in the SsK12 group (16.2% vs. 48.6%, p < 0.01), whereas another placebo-controlled RCT over four school terms (n = 1314, 5-14 years) found no significant difference (7.8% vs. 8.8%, p 0.34) with SsK12 (administered on school days). Another trial found daily SsK12 to significantly protect children (n = 250, 6-7 years) against chronic adenoiditis exacerbation over 3 months compared to no treatment (71.7% vs. 100%, p < 0.0001). The one placebo-controlled RCT in adults that studied the use of SsK12 for acute pharyngotonsillitis (concurrently with penicillin) showed no significant benefit. In all trials, SsK12 was safe and well tolerated.
CONCLUSIONS: SsK12 appears safe and well tolerated. However, further RCTs are required to establish its role as a prophylactic therapy, particularly among patients experiencing frequent exacerbations of pharyngitis. In the acute setting, SsK12 is unlikely to be effective if given concurrently with antibiotics; however, further RCTs should establish its role as an alternative to antibiotics in nonsevere cases or when prescribed after antibiotic therapy for the prevention of disease recurrence and/or secondary infection.

PMID: 30616011 [PubMed - indexed for MEDLINE]

Enhanced Safety Surveillance of Seasonal Quadrivalent Influenza Vaccines in English Primary Care: Interim Analysis.

Adv Ther. 2018 Aug;35(8):1199-1214

Authors: de Lusignan S, Dos Santos G, Byford R, Schuind A, Damaso S, Shende V, McGee C, Yonova I, Ferreira F

Abstract
INTRODUCTION: The European Medicines Agency (EMA) requires vaccine manufacturers to conduct enhanced safety surveillance (ESS) of seasonal influenza vaccines including a near real-time evaluation of collected data. The objective was to identify whether the use of passive surveillance or active surveillance provides different results of reported adverse events of interest (AEIs) by specified age strata and AEI type. We report the weekly incidence rates of AEIs within 7 days following seasonal influenza vaccination using passive and active surveillance.
METHODS: AEIs were collected within 7 days of vaccination from ten general practices predominantly administering inactivated quadrivalent influenza vaccine (IIV4, Fluarix Tetra, GSK). Vaccinees completed an adverse drug reaction (ADR) card. ADR card and medically attended AEIs data were recorded in practice electronic health records. We report the outcome of the first 5 weeks of safety surveillance (September 12, 2016-October 16, 2016); in an exploratory analysis, rates of AEI for IIV4 are compared to those passively reported through a sentinel network.
RESULTS: Practices vaccinated 13.1% (12,864/98,091) of their registered population; 5.6% (95% CI 5.20-6.00) of them reported AEIs, none serious. The most frequent were respiratory 2.60% (95% CI 2.33-2.88), musculoskeletal 1.82% (95% CI 1.59-2.05) and neurological 1.05% (95% CI 0.88-1.23). AEIs were more frequently reported for adults than for children; 5.91% (95% CI 5.49-6.34) compared to 1.49% (95% CI 0.69-2.29); 47.18% of the adults reported AEI using the ADR card, none were returned for subjects < 18 years old. The frequency of AEIs reporting was higher, 6.88% (95% CI 6.35-7.42) vs. 3.30% (95% CI 2.68-3.96, 100/3028, p < 0.000), through ESS than passive surveillance.
CONCLUSION: The ESS did not reveal any safety signal and we demonstrated the feasibility of conducting ESS following EMA recommendations. The use of a customised ADR card led to a doubling of AEIs reports over passive surveillance in adults.
FUNDING: GlaxoSmithKline Biologicals SA, Wavre, Belgium.

PMID: 29995300 [PubMed - indexed for MEDLINE]

A randomised phase II study of second-line XELIRI regimen versus irinotecan monotherapy in advanced biliary tract cancer patients progressed on gemcitabine and cisplatin.

Br J Cancer. 2018 08;119(3):291-295

Authors: Zheng Y, Tu X, Zhao P, Jiang W, Liu L, Tong Z, Zhang H, Yan C, Fang W, Wang W

Abstract
BACKGROUND: The majority of advanced biliary tract cancer (ABTC) patients will progress after gemcitabine and cisplatin (GP) doublet therapy, while the standard second-line regimen has not been established. We conducted this study to assess the efficacy and safety of second-line irinotecan and capecitabine (XELIRI) regimen vs. irinotecan monotherapy in ABTC patients progressed on GP.
METHODS: Sixty-four GP refractory ABTC patients were randomised to either irinotecan 180 mg/m2 on day 1 plus capecitabine 1000 mg/m2 twice daily on days 1-10 of a 14-day cycle (XELIRI-arm) or single-agent irinotecan 180 mg/m2 on day 1 of a 14-day cycle (IRI-arm). Treatments were repeated until disease progression or unacceptable toxicity occurred.
RESULTS: A total of 60 patients were included in the analysis. For XELIRI and IRI-arms, respectively, the median PFS was 3.7 vs. 2.4 months, 9-month survival rate 60.9% vs. 32.0%, median OS 10.1 vs. 7.3 months, and disease control rate 63.3% vs. 50.0%. The most common grade 3 or 4 toxicities were leucopaenia and neutropaenia.
CONCLUSIONS: This randomised, phase II study of irinotecan-containing regimens in good PS second-line ABTC patients showed a clear benefit of XELIRI regimen over irinotecan monotherapy in prolonging PFS, with acceptable toxicity.

PMID: 29955136 [PubMed - indexed for MEDLINE]

Increased risk of thiopurine-related adverse events in elderly patients with IBD.

Aliment Pharmacol Ther. 2019 Aug 19;:

Authors: Calafat M, Mañosa M, Cañete F, Ricart E, Iglesias E, Calvo M, Rodríguez-Moranta F, Taxonera C, Nos P, Mesonero F, Martín-Arranz MD, Mínguez M, Gisbert JP, García-López S, de Francisco R, Gomollón F, Calvet X, Garcia-Planella E, Rivero M, Martínez-Cadilla J, Argüelles F, Arias L, Cimavilla M, Zabana Y, Domènech E, ENEIDA registry of GETECCU

Abstract
BACKGROUND: Thiopurines are the most widely used immunosuppressants in IBD although drug-related adverse events (AE) occur in 20%-30% of cases.
AIM: To evaluate the safety of thiopurines in elderly IBD patients METHODS: Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine-related AEs registered in the ENEIDA database were compared.
RESULTS: Out of 48 752 patients, 1888 thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2-55] vs 32 [IQR 5-82] months; P < .001). Patients starting >60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P < .001). Elderly age and female sex were independent risk factors for most AEs.
CONCLUSION: In elderly IBD patients, thiopurines are associated with an increased risk of non-infectious, non-neoplastic, AEs.

PMID: 31429097 [PubMed - as supplied by publisher]