Health care professionals knowledge and perception of pharmacovigilance in a tertiary care teaching hospital in Amman, Jordan.

J Eval Clin Pract. 2017 Jun;23(3):608-613

Authors: Abu Hammour K, El-Dahiyat F, Abu Farha R

Abstract
RATIONALE, AIMS, AND OBJECTIVES: Underreporting of adverse drug reactions (ADRs) by health care professionals is a common inherent health problem encountered in many countries. This could be explained by the lack of awareness and knowledge about the guidelines to follow to identify and report ADRs. Thus, this study aimed to evaluate the awareness, knowledge, and perceptions among medical doctors and nurses regarding their role as ADRs reporters in Jordan.
METHODS: A cross-sectional study was conducted between September 2015 to January 2016 at the Jordan University Hospital in Amman. During the study period, a total of 670 validated questionnaires were distributed to medical doctors and nurses in different departments.
RESULTS: Most of health care professionals were not aware of the concept of pharmacovigilance. Medical doctors showed a better overall knowledge compared with nurses (P < .05). Interestingly, despite the low level of awareness, the majority of respondents believed in the necessity of reporting ADRs.
CONCLUSION: Although there is a low level of awareness among health care professionals regarding pharmacovigilance, there is strong agreement among them about the necessity of reporting ADRs and attending educational sessions about pharmacovigilance which will help them to improve the quality of services they provide.

PMID: 28090715 [PubMed - indexed for MEDLINE]

Impact of a Pharmacy-Cardiology Collaborative Practice on Dofetilide Safety Monitoring.

Ann Pharmacother. 2017 Jan;51(1):39-43

Authors: Quffa LH, Panna M, Kaufmann MR, McKillop M, Dietrich NM, Franck AJ

Abstract
BACKGROUND: Limited studies have been published examining dofetilide's postmarketing use and its recommended monitoring.
OBJECTIVE: To evaluate the impact of a collaborative pharmacy-cardiology antiarrhythmic drug (AAD) monitoring program on dofetilide monitoring.
METHODS: This retrospective cohort study was performed to assess if a novel monitoring program improved compliance with dofetilide-specific monitoring parameters based on the Food and Drug Administration's Risk Evaluation and Mitigation Strategy.
RESULTS: A total of 30 patients were included in the analysis. The monitoring parameters evaluated included electrocardiogram, serum potassium, serum magnesium, and kidney function. The primary outcome evaluated was the composite of these dofetilide monitoring parameters obtained in each cohort. In the standard cohort, 245 of 352 (69.6%) monitoring parameters were completed versus 134 of 136 (98.5%) in the intervention group ( P < 0.05).
CONCLUSION: A collaborative pharmacy-cardiology AAD monitoring program was associated with a significant improvement in dofetilide monitoring. This improvement could potentially translate into enhanced patient safety outcomes, such as prevention of adverse drug reactions and decreased hospitalizations.

PMID: 27630191 [PubMed - indexed for MEDLINE]

Efficacy and safety of mirabegron for the treatment of neurogenic detrusor overactivity-Prospective, randomized, double-blind, placebo-controlled study.

Neurourol Urodyn. 2018 Mar 31;:

Authors: Krhut J, Borovička V, Bílková K, Sýkora R, Míka D, Mokriš J, Zachoval R

Abstract
AIMS: To assess the efficacy and safety of mirabegron in the treatment of neurogenic detrusor overactivity.
METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled study was conducted in three tertiary centers, and included 78 patients suffering from spinal cord injury or multiple sclerosis. Patients were randomized for Mirabegron 50 mg (Group A) or placebo (Group B). Urodynamic parameters, the 24 h pad-weight test, and patient-reported outcomes were assessed. Safety assessments included monitoring the incidence and severity of adverse events. Changes in time and differences between groups were assessed with nonparametric Kruskal-Wallis one-way analysis of variance; P ≤ 0.05 was considered statistically significant.
RESULTS: In total, 66 patients were eligible for inclusion in the final analysis. There was a significant increase of volume at the first detrusor contraction (P = 0.00047) and an improvement in bladder compliance (P = 0.0041) in the mirabegron group compared with the placebo-treated group, whereas the increase in cystometric capacity did not reach statistical significance (P = 0.061). There was a clear tendency to reduced urine leakage (P = 0.056) in Group A. There were significant changes in all the patient-reported outcomes, favoring the mirabegron group. The incidence of drug-related adverse events was 3.13%.
CONCLUSIONS: Mirabegron (50 mg) improved both urodynamic variables and patient-reported outcomes in patients with NDO. The treatment was tolerated well.

PMID: 29603781 [PubMed - as supplied by publisher]

Treatment outcomes in older patients with advanced gastrointestinal stromal tumor (GIST).

J Geriatr Oncol. 2018 Mar 27;:

Authors: Rutkowski P, Bylina E, Lugowska I, Teterycz P, Klimczak A, Streb J, Czarnecka AM, Osuch C

Abstract
BACKGROUND: The aim of the study was to analyze the treatment results of advanced GIST in the largest, homogenous series of older patients.
METHODS: Between 2001 and 2016, 686 patients with metastatic/unresectable GIST were treated initially with imatinib and 656 were included in the analysis. Subsequently 232 patients were treated with sunitinib after imatinib failure. We have analyzed the outcomes of patients who have been treated with the tyrosine kinase inhibitor at the age ≥ 70 years and compared to control group of patients younger than 70 years old.
RESULTS: In the group of patients treated with imatinib, 139 (21%) started therapy at the age of at least 70 years (median age of the entire cohort: 60). Median progression-free survival (PFS) on 1st line imatinib did not differ between patients ≥70 yo (years old) and < 70yo (38.5 vs 44.9 months), but median overall survival (OS) was significantly better for younger patients (81 months vs. 50; p = 0.0001; although disease-specific survival - DSS was similar). Distribution of primary tumor mutational status was generally similar in older and younger patients. Permanent dose reduction (300-100 mg/day) was required for 23 patients (16.9%) in the older group and was significantly more frequent as compared to younger patients (5%). Drug-related adverse events were mainly of grades 1/2, but grade 3/4 toxicity occurred more frequently in older (14.7%) than in younger patients (3.8%). Similarly in group of patients treated with second-line sunitinib median PFS and DSS were comparable in groups of patients ≥70 yo (n = 55) and < 70yo (9.7 months vs 10.3 months; p = 0.7, and 21.5 vs 22.9 months). >40% of patients in both groups required dose adjustments to 37.5-25 mg daily.
CONCLUSIONS: Our study confirms that current therapy of advanced GIST with tyrosine kinase inhibitors (both in 1st and 2nd line) in older patients enable to achieve the similar disease control rate and final outcomes as in younger patients, but it demands close cooperation of experienced oncologist with patients for dose modifications and side effects management. Limitation of our study is that the patients did not undergo a comprehensive geriatric assessment, what might be helpful for personalized management of patients. Nevertheless, we confirm that older patients with GIST should not receive less treatment irrespective of comorbidities.

PMID: 29602734 [PubMed - as supplied by publisher]

Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: A systematic review.

Crit Rev Oncol Hematol. 2018 Jan;121:90-100

Authors: Duregon F, Vendramin B, Bullo V, Gobbo S, Cugusi L, Di Blasio A, Neunhaeuserer D, Zaccaria M, Bergamin M, Ermolao A

Abstract
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is the most common neurological and clinically relevant side effect of many commonly used chemotherapeutic agents. Moreover, little effort has been done to investigate the potentially beneficial effects of specific exercises to counteract the CIPN symptoms.
OBJECTIVE: This document aims to summarize and analyze systematically the current body of evidence about the effects of specific exercise protocols on CIPN symptoms, balance control, physical function and quality of life in patients with CIPN.
LITERATURE SURVEY: Specific terms were identified for the literature research in MEDLINE, Scopus, Bandolier, PEDro, and Web of Science.
METHODOLOGY: Five manuscripts were considered eligible for this review. Quality appraisal distinguished two studies as high quality investigations while three with low quality. Results were summarized in the following domains: "CIPN symptoms", "Static balance control", "Dynamic balance control", "Quality of life and Physical function".
SYNTHESIS: Significant improvements were detected on postural control. Additionally, patients' quality of life and independence were found ameliorated after exercise sessions. Combined exercise protocols including endurance, strength and sensorimotor training showed larger improvements.
CONCLUSIONS: This systematic review comes from a highly selected but small source of data. Nevertheless, specific exercise for cancer patients undergoing chemotherapy with CIPN symptoms should be recommended since these interventions appeared as feasible and have been demonstrated as useful tools to counteract some of the limitations due to chemotherapy.

PMID: 29198853 [PubMed - indexed for MEDLINE]

Trial of dextromethorphan/quinidine to treat levodopa-induced dyskinesia in Parkinson's disease.

Mov Disord. 2017 Jun;32(6):893-903

Authors: Fox SH, Metman LV, Nutt JG, Brodsky M, Factor SA, Lang AE, Pope LE, Knowles N, Siffert J

Abstract
BACKGROUND: Nondopaminergic pathways represent potential targets to treat levodopa-induced dyskinesia in Parkinson's disease (PD). This pilot-study (NCT01767129) examined the safety/efficacy of the sigma-1 receptor-agonist and glutamatergic/monoaminergic modulator, dextromethorphan plus quinidine (to inhibit rapid dextromethorphan metabolism), for treating levodopa-induced dyskinesia.
METHODS: PD patients were randomized to dextromethorphan/quinidine (45 mg/10 mg twice daily)/placebo in two 2-week double-blind, crossover treatment periods, with intervening 2-week washout. After 14 days, a 2-hour intravenous levodopa-infusion was administered. Patient examinations were videotaped before infusion ("off" state) and every 30 minutes during and afterwards until patients returned to "off." The primary endpoint was dyskinesia-severity during infusion measured by Unified Dyskinesia Rating Scale part 3 area-under-curve scores (blinded expert rated). Additional endpoints included other dyskinesia/motor assessments, global measures of clinical-change, and adverse-events.
RESULTS: A total of 13 patients were randomized and completed the study (efficacy-evaluable population). Dyskinesia-severity was nonsignificantly lower with dextromethorphan/quinidine than placebo during infusion (area-under-curve 966.5 vs 1048.8; P = .191 [efficacy-evaluable patients]), and significantly lower in a post-hoc sensitivity analysis of the per-protocol-population (efficacy-evaluable patients with ≥ 80% study-drug-compliance, n = 12) when measured from infusion start to 4-hours post-infusion completion (area-under-curve 1585.0 vs 1911.3; P = .024). Mean peak dyskinesia decreased significantly from infusion-start to return to "off" (13.3 vs 14.9; P = .018 [efficacy-evaluable patients]). A total of 9 patients rated dyskinesia "much/very much improved" on dextromethorphan/quinidine versus 1-patient on placebo. Dextromethorphan/quinidine did not worsen PD-motor scores, was generally well tolerated, and was associated with more frequent adverse events.
CONCLUSION: This study provides preliminary evidence of clinical benefit with dextromethorphan/quinidine for treating levodopa-induced dyskinesia in PD. Larger studies with a longer treatment duration need to corroborate these early findings. © 2017 International Parkinson and Movement Disorder Society.

PMID: 28370447 [PubMed - indexed for MEDLINE]

13 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 2018/03/30

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.

12 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 2018/03/30

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.

Primaquine Pharmacokinetics in Lactating Women and Breastfed Infant Exposures.

Clin Infect Dis. 2018 Mar 24;:

Authors: Ellen Gilder M, Hanpithakphong W, Hoglund RM, Tarning J, Htun Win H, Hilda N, Chu CS, Bancone G, Carrara VI, Singhasivanon P, White NJ, Nosten F, McGready R

Abstract
Background: Primaquine is the only drug providing radical cure of Plasmodium vivax malaria. It is not recommended for breastfeeding women as it causes hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient individuals, and breast milk excretion and thus infant exposure are not known.
Methods: Healthy G6PD normal breastfeeding women with previous P.vivax infection and their healthy G6PD normal infants between 28 days and 2 years old were enrolled. Mothers took primaquine 0.5 mg/kg/day for 14 days. Primaquine and carboxyprimaquine concentrations were measured in maternal venous plasma, capillary plasma, and breast milk samples and infant capillary plasma samples taken on days 0, 3, 7, and 13.
Results: In 20 mother-baby pairs primaquine concentrations were below measurement thresholds in all but one infant capillary plasma sample (that contained primaquine 2.6 ng/mL) and carboxyprimaquine was likewise unmeasurable in the majority of infant samples (maximum value 25.8 ng/mL). The estimated primaquine dose received by infants, based on measured breast milk levels, was 2.98 µg/kg/day (i.e. ~0.6% of a hypothetical infant daily dose of 0.5 mg/kg). There was no evidence of drug-related hemolysis in the infants. Maternal levels were comparable to non-lactating patients, and adverse events in mothers were mild.
Conclusions: The concentrations of primaquine in breast milk are very low and therefore very unlikely to cause adverse effects in the breast-feeding infant. Primaquine should not be withheld from mothers breastfeeding infants or young children. More information is needed in neonates.

PMID: 29590311 [PubMed - as supplied by publisher]

Liver and statins: a critical appraisal of the evidence.

Curr Med Chem. 2018 Mar 26;:

Authors: Licata A, Giammanco A, Minissale MG, Pagano S, Petta S, Averna M

Abstract
Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatotoxicity, it will then focus on the recent Genome-Wide Association Studies (GWAS) concerning the transporter genes, Cytochrome P450 (CYP), organic anion-transporting polypeptide (OATP) and ABCB1 and ABCC1, which seem to play a role in the development of clinically relevant adverse events. Finally, we appraise the evidence for and against the use of statins in metabolic syndrome and in HCV-infected patients, in terms of their safety and efficacy in cardiovascular events.

PMID: 29589533 [PubMed - as supplied by publisher]

Potentially inappropriate medication in the elderly: a systematic review of validated explicit criteria.

Eur J Clin Pharmacol. 2018 Mar 27;:

Authors: Motter FR, Fritzen JS, Hilmer SN, Paniz ÉV, Paniz VMV

Abstract
PURPOSE: Potentially inappropriate medication (PIM) use causes preventable adverse drug reactions in older patients. Several assessment tools have been published to identify and avoid PIM use. In this systematic literature review, we aim to provide summaries and comparisons of validated PIMs lists published between 1991 and 2017 internationally.
METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), we performed a systematic review of articles describing the development and validation of criteria for identification of PIMs among older people published between January 1991 and April 2017. The searches were conducted on PUBMED, AgeLine, Academic Search, Academic Search Premier, and CINAHL. We identified the most common medications/classes described as PIM. We also identified the drug-disease interactions and drug-drug interactions reported among criteria.
RESULTS: From 2933 articles screened, 36 met our inclusion criteria. The majority used the Delphi method to validate their criteria. We identified 907 different medications/classes, 536 different drug disease interactions involving 84 diseases/conditions, and 159 drug-drug interactions. Benzodiazepines and nonsteroidal anti-inflammatory drugs were the medications most commonly reported as potentially inappropriate for older people.
CONCLUSION: Although approaches aimed at detecting inappropriate prescribing have intensified in recent years, we observed limited overlap between different PIM lists. Additionally, some PIM lists did not provide special considerations of use and alternative therapies to avoid PIMs. These facts may compromise the use of PIM lists in clinical practice. Future PIM lists should integrate information about alternative therapies and special considerations of use in order to help clinicians in the drug prescription.

PMID: 29589066 [PubMed - as supplied by publisher]

Severe immune thrombocytopaenia in a patient taking benznidazole for chronic Chagas disease.

BMJ Case Rep. 2018 Mar 27;2018:

Authors: Crespillo-Andújar C, Calbacho Robles M, Norman FF, Pérez-Molina JA

Abstract
Chagas disease is a parasitic disease that mostly affects Latin American countries, but it has currently become a worldwide epidemic due to migration. Both drugs marketed for its treatment (benznidazole and nifurtimox) are associated with a high rate of adverse reactions. Benznidazole is preferred initially because of its more favourable toxicity profile and perceived greater efficacy. Hypersensitivity dermatological reactions, gastrointestinal and neurological disturbances represent the most common drug-related adverse events. General symptoms such as fever, arthralgia, myalgia or bone marrow depression (leucopaenia) are seen less frequently. We describe the case of a 33-year-old woman with chronic Chagas disease who presented with acute gingival bleeding and severe thrombocytopaenia, probably related to benznidazole treatment. Temporal association with drug initiation and recovery after treatment withdrawal were demonstrated. Clinicians should be aware of the possible association between immune thrombocytopaenia and benznidazole, even though the pathogenesis remains unclear at present.

PMID: 29588298 [PubMed - in process]

Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial.

J Clin Oncol. 2018 Mar 27;:JCO2017760793

Authors: Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM

Abstract
Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee. Results Overall, 243 patients were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median follow-up of 18 months, 40% continued to receive treatment. The objective response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort. Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3 months), and median progression-free survival was 14.7 months (95% CI, 11.3 to 18.5 months). Of 70 patients treated past conventional disease progression, 61% of those evaluable had stable or further reduced target tumor burdens. The most common grade 3 to 4 drug-related adverse events were lipase increases (5%), neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were considered treatment related. Conclusion With extended follow-up, responses to nivolumab were frequent and durable. Nivolumab seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.

PMID: 29584546 [PubMed - as supplied by publisher]

Upper Airway Stimulation for Obstructive Sleep Apnea: 5-Year Outcomes.

Otolaryngol Head Neck Surg. 2018 Mar 01;:194599818762383

Authors: Woodson BT, Strohl KP, Soose RJ, Gillespie MB, Maurer JT, de Vries N, Padhya TA, Badr MS, Lin HS, Vanderveken OM, Mickelson S, Strollo PJ

Abstract
Objective To present 5-year outcomes from a prospective cohort of patients with obstructive sleep apnea (OSA) who were treated with upper airway stimulation (UAS) via a unilateral hypoglossal nerve implant. Study Design A multicenter prospective cohort study. Setting Industry-supported multicenter academic and clinical trial. Methods From a cohort of 126 patients, 97 completed protocol, and 71 consented to a voluntary polysomnogram. Those having continuous positive airway pressure failure with moderate to severe OSA, body mass index <32 kg/m2, and no unfavorable collapse on drug-induced sleep endoscopy were enrolled in a phase 3 trial. Prospective outcomes included apnea-hypopnea index (AHI), oxygen desaturation index, and adverse events, as well as measures of sleepiness, quality of life, and snoring. Results Patients who did and did not complete the protocol differed in baseline AHI, oxygen desaturation index, and Functional Outcomes of Sleep Questionnaire scores but not in any other demographics or treatment response measures. Improvement in sleepiness (Epworth Sleepiness Scale) and quality of life was observed, with normalization of scores increasing from 33% to 78% and 15% to 67%, respectively. AHI response rate (AHI <20 events per hour and >50% reduction) was 75% (n = 71). When a last observation carried forward analysis was applied, the responder rate was 63% at 5 years. Serious device-related events all related to lead/device adjustments were reported in 6% of patients. Conclusions Improvements in sleepiness, quality of life, and respiratory outcomes are observed with 5 years of UAS. Serious adverse events are uncommon. UAS is a nonanatomic surgical treatment with long-term benefit for individuals with moderate to severe OSA who have failed nasal continuous positive airway pressure.

PMID: 29582703 [PubMed - as supplied by publisher]

Long-term tolerability, immunogenicity and efficacy of Nuwiq® (human-cl rhFVIII) in children with severe haemophilia A.

Haemophilia. 2018 Mar 26;:

Authors: Klukowska A, Szczepański T, Vdovin V, Knaub S, Bichler J, Jansen M, Dzhunova I, Liesner RJ

Abstract
INTRODUCTION: Nuwiq® (human-cl rhFVIII, simoctocog alfa) is a 4th generation recombinant human FVIII, without chemical modification or fusion with any other protein, produced in a human cell line.
AIM/METHODS: This study (GENA-13) was an extension of the GENA-03 study in which previously treated children aged 2-12 years with severe haemophilia A received Nuwiq® prophylaxis for ≥6 months. GENA-13 examined long-term tolerability, immunogenicity and efficacy of Nuwiq® prophylaxis in children.
RESULTS: Of 59 patients enrolled in GENA-03, 49 continued Nuwiq® prophylaxis in GENA-13 for a median (range) of 30.0 (9.5-52.0) months. No patient withdrew due to drug-related adverse events or developed inhibitors. Only 2 of 20 518 infusions were associated with possibly related adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR) was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for all bleeds. Younger children (2-5 years) had lower ABRs than children aged 6-12 years. Annualized bleeding rates were reduced in GENA-13 vs GENA-03, especially for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 [95% CI: 0.11, 0.74]). Nuwiq® efficacy was rated as excellent/good in the treatment of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq® was rated as excellent for all 17 assessed procedures.
CONCLUSION: Long-term treatment with Nuwiq® for the prevention of bleeds in children with severe haemophilia A was well tolerated, effective and reduced spontaneous bleeding by up to 70% compared with GENA-03.

PMID: 29582516 [PubMed - as supplied by publisher]

Concurrent Chemoradiotherapy with or without Anti-EGFR-Targeted Treatment for Stage II-IVb Nasopharyngeal Carcinoma: Retrospective Analysis with a Large Cohort and Long Follow-up.

Theranostics. 2017;7(8):2314-2324

Authors: You R, Hua YJ, Liu YP, Yang Q, Zhang YN, Li JB, Li CF, Zou X, Yu T, Cao JY, Zhang MX, Jiang R, Sun R, Mo HY, Guo L, Cao KJ, Lin AH, Sun Y, Qian CN, Ma J, Chen MY

Abstract
We examined the benefits of the combination of anti-EGFR targeted treatment, cetuximab (CTX) or nimotuzumab (NTZ) and concurrent platinum-based chemoradiotherapy (CCRT) compared with CCRT alone in patients with stage II - IVb nasopharyngeal carcinoma (NPC). A total of 1,628 eligible patients with stage II - IVb NPC, who received CCRT (three cycles of 100 mg/m2 cisplatin every 3 weeks with intensity-modulated radiotherapy) with or without CTX or NTZ between June 2009 and December 2013 were included in the analysis. Using propensity scores to adjust for potential prognostic factors, a well-balanced cohort of 878 patients was created by matching each patient who received CTX or NTZ plus CCRT with no more than four patients who received CCRT alone (1:4). Efficacy and safety were compared between CTX/NTZ plus CCRT and CCRT alone arms. Compared with CCRT alone, treatment with CTX/NTZ plus CCRT was associated with a significantly increased overall survival (3-year OS, 96.6% vs. 92.9%, P = 0.015), improved disease-free survival (3-year DFS, 93.5% vs 86.9%, P = 0.028), and improved distant metastasis-free survival (3-year DMFS, 94.6% vs 89.3%, P = 0.030). Increased rate of CTX related-skin reaction and mucositis was observed in the CTX plus CCRT arm. Multivariate analysis demonstrated the combination of CTX/NTZ was a significant protective factor for OS, DFS, and DMFS in patients treated with CCRT. Our analysis suggests that the addition of CTX/NTZ to CCRT is more effective for maximizing survival in patients with stage II-IVb NPC compared with CCRT alone.

PMID: 28740554 [PubMed - indexed for MEDLINE]

Safety and Immunogenicity of a 9-Valent Human Papillomavirus Vaccine Administered to 9- to 15-Year-Old Japanese Girls.

Jpn J Infect Dis. 2017 Jul 24;70(4):368-373

Authors: Iwata S, Murata S, Rong Han S, Wakana A, Sawata M, Tanaka Y

Abstract
A 9-valent human papillomavirus (HPV 6/11/16/18/31/33/45/52/58) virus-like particle vaccine (9vHPV) has been proven highly efficacious in preventing anogenital diseases related to HPV, in a pivotal phase III study for women aged 16-26 years. Here, we report the results of an open-label phase III study conducted to bridge the gap between the findings in women aged 16-26 years and Japanese girls aged 9-15 years. All subjects (n = 100) received a 3-dose regimen of 9vHPV vaccine on day 1 and at months 2 and 6. Anti-HPV serological assays were performed on day 1 and at months 7, 12, 24, and 30. At month 7 (4 weeks after the third dose), 100% of the subjects exhibited seroconversion for each type of HPV. Increases in geometric mean of the titers for anti-HPV 6/11/16/18/31/33/45/52/58 in the subjects were similar to those in Japanese women aged 16-26 years in a previous phase III study. Persistence of the anti-HPV response was observed for 2 years after administration of the third dose. In addition, administration of the 9vHPV vaccine was generally well-tolerated in Japanese girls.

PMID: 28003597 [PubMed - indexed for MEDLINE]

[MODERN ASPECTS OF THE SAFE USE OF EXTENSION QT INTERVAL MEDICINES.]

Anesteziol Reanimatol. 2016 Sep;61(5):386-390

Authors: Shikh EV, Ismaailov AD, Dorofeeva MN, Sizava ZM

Abstract
Prolongation of QTinterval is apredictor offatal cardiac arrhythmias and sudden death. In clinical practice, medicines with possible and conditional risk of QTprolongation are combine. The danger of such interactions could be enhanced if medi- cines interact themselves at metabolic rate. The interaction of drugs with possible and conditional risk of QTprolongation and interaction of these drugs with drugs that can influence the metabolic activity of cytochrome P450 isoenzymes require specific attention from physicians. Predictability of QTprolongation by drug-drug interactions at metabolic rate in drug administration will increase the safety of pharmacotherapy of drugs with possible and conditional risk of QTprolongation.

PMID: 29489109 [PubMed - indexed for MEDLINE]

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 2018/03/27

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.

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 2018/03/27

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.