Carbon nanotubes: Properties, biomedical applications, advantages and risks in patients and occupationally-exposed workers.

Int J Immunopathol Pharmacol. 2015 Mar;28(1):4-13

Authors: Lamberti M, Pedata P, Sannolo N, Porto S, De Rosa A, Caraglia M

Abstract
Since the beginning of the 21st century, carbon-based nanomaterials (CNTs) have been introduced in pharmacy and medicine for drug delivery system in therapeutics. CNTs have proved able to transport a wide range of molecules across membranes and into living cells; therefore, they have attracted great interest in biomedical applications such as advanced imaging, tissue regeneration, and drug or gene delivery. Although there are many data on the advantages in terms of higher efficacy and less adverse effects, several recent findings have reported unexpected toxicities induced by CNTs. The dose, shape, surface chemistry, exposure route, and purity play important roles in these differential toxicities. Mapping these risks as well as understanding their molecular mechanisms is a crucial step in the development of any CNT-containing nanopharmaceuticals. This paper seeks to provide a comprehensive review of all articles published on cellular response to CNTs, underlining their therapeutic applications and possible toxicity in patients and occupationally exposed workers.

PMID: 25816400 [PubMed - indexed for MEDLINE]

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

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

These pubmed results were generated on 2017/03/31

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.

New pharmacological opportunities for the treatment of invasive mould diseases.

J Antimicrob Chemother. 2017 Mar 01;72(suppl_1):i48-i58

Authors: Ledoux MP, Toussaint E, Denis J, Herbrecht R

Abstract
Recently, several randomized studies have been published that will shape treatment decisions in the prevention and management of invasive mould infections. Liposomal amphotericin B is an option for empirical or targeted treatment of invasive aspergillosis or mucormycosis, but for prophylaxis therapy, the triazole class now predominates. The triazole voriconazole is currently regarded as a drug of choice for the treatment of proven or probable invasive aspergillosis, and has shown significantly higher response rates than amphotericin B deoxycholate in this setting, with fewer severe drug-related adverse events. Isavuconazole, the newest triazole agent, offers the advantages of once-daily dosing, a wider spectrum of antifungal activity than voriconazole, predictable pharmacokinetics and fewer CYP enzyme-mediated drug interactions. A recent large randomized clinical trial showed mortality to be similar under isavuconazole or voriconazole in patients with invasive mould disease, with fewer drug-related adverse events in isavuconazole-treated patients. Another study has indicated that isavuconazole is also effective in mucormycosis infections but patient numbers were small and confirmation is awaited. Experimental studies combining different drug classes with antimould activity have been promising, but the clinical database is limited. A large randomized trial of combination therapy compared voriconazole plus the echinocandin anidulafungin versus voriconazole monotherapy in patients with invasive aspergillosis. Results showed the overall response rate to be similar, but combination therapy improved survival for the subpopulation of patients in whom the diagnosis was confirmed by serum and/or bronchoalveolar lavage fluid galactomannan positivity. This active field of research is likely to continue evolving rapidly in the coming years.

PMID: 28355467 [PubMed - in process]

Nivolumab-associated colitis mimicking ulcerative colitis.

Clin Gastroenterol Hepatol. 2017 Mar 25;:

Authors: Kubo K, Kato M, Mabe K

PMID: 28351793 [PubMed - as supplied by publisher]

Thinking Clinically from the Beginning: Early Introduction of the Pharmacists' Patient Care Process.

Am J Pharm Educ. 2016 Dec 25;80(10):164

Authors: Rivkin A

Abstract
Objective. To describe a student-centered teaching method used to introduce a pharmacist patient care process (PPCP) during the first year of a doctor of pharmacy (PharmD) program. Design. In the fall of 2014, a cohort of students (n=85) began an integrated pharmacotherapy (IPT) course sequence in the first semester of pharmacy school. The first course in this sequence laid the foundation for the delivery of care, focusing on the individual components of a PPCP. Faculty member used a variety of teaching methods in the course to introduce medication history taking, identification of drug-related problems, identifying components of a patient case, and learning/beginning to write subjective, objective, assessment, plan (SOAP) notes. Students' SOAP notes submissions and performance on multiple-choice examinations were evaluated to demonstrate evidence of learning. Students also completed online course evaluations. Assessment. Course-imbedded assessments were designed to measure student learning related to individual School of Pharmacy outcomes and course learning objectives. The mean individual student score on exam questions related to the PPCP topics was 83.7%±18.8%. The majority of students (86%-88%) rated their progress on achieving course learning objectives as "substantial" or "exceptional." Students also enrolled in the introductory pharmacy practice experience (IPPE) in a community setting after completing the first IPT. The students performed significantly better than a historic cohort in identifying actual and potential drug therapy problems. Conclusion. The described teaching methods, when introduced in early curricular stages, are effective in building a foundation for learning PPCP.

PMID: 28179713 [PubMed - indexed for MEDLINE]

Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.

Am J Pharm Educ. 2016 Oct 25;80(8):131

Authors: Sawant RV, Beatty CR, Sansgiry SS

Abstract
Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.

PMID: 27899827 [PubMed - indexed for MEDLINE]

The FDA Revises Boxed Warning For Fluoroquinolones-Again.

Am J Nurs. 2016 Sep;116(9):22-3

Authors: Aschenbrenner DS

PMID: 27560334 [PubMed - indexed for MEDLINE]

Sumatriptan Patch is Temporarily Suspended.

Am J Nurs. 2016 Sep;116(9):22

Authors: Aschenbrenner DS

PMID: 27560333 [PubMed - indexed for MEDLINE]

Anaphylaxis.

Prim Care. 2016 Sep;43(3):477-85

Authors: Hernandez L, Papalia S, Pujalte GG

Abstract
Anaphylaxis is an acute, systemic reaction mediated by immunoglobulin E hypersensitivity. Release of bioactive factors causes vasodilation and bronchiole constriction that can lead to hypotensive shock and asphyxiation. Differential diagnosis includes acute asthma, localized angioedema, syncope, and anxiety/panic attacks. Diagnostic tests lack specificity. Clinical diagnosis is based on demonstration of specific airway or cardiovascular compromise within proximity of allergen exposure. Treatment includes epinephrine, antihistamines, fluid resuscitation, and airway management. Prevention focuses on awareness/avoidance of triggers, implementation of personalized action plans, as well as immune modulation by desensitization in a closely controlled setting where available.

PMID: 27545736 [PubMed - indexed for MEDLINE]

"Adaptive pathways" to drug authorisation: adapting to industry?

BMJ. 2016 Aug 16;354:i4437

Authors: Davis C, Lexchin J, Jefferson T, Gøtzsche P, McKee M

PMID: 27531201 [PubMed - indexed for MEDLINE]

Safety and tolerability of regadenoson for myocardial perfusion imaging - first Danish experience.

Scand Cardiovasc J. 2016 Jun;50(3):180-6

Authors: Pape M, Zacho HD, Aarøe J, Eggert Jensen S, Petersen LJ

Abstract
OBJECTIVES: Evaluating safety and tolerability of the selective A2A receptor agonist, regadenoson, in patients referred for single photon emission computed tomography myocardial perfusion imaging (MPI).
DESIGN: Observational study of patients referred for MPI stress testing using a 400 μg regadenoson (Rapiscan(®)) bolus. Hemodynamic variables and severity of adverse events (AE) were recorded before, during, and after administration.
RESULTS: A total of 232 patients were included. One or more AE were reported in 90% of patients; the AEs were graded mostly mild to moderate in severity, resolved spontaneously, and were mainly dyspnea, headache, and chest pain. No advanced heart block or bronchospasm were seen. Transient ST-segment changes developed in 10 patients. The maximum increase in heart rate was 19 ± 11 beats/minute. The mean systolic blood pressure decreased from 144 to 139 mmHg (p < 0.0001). Medical intervention was required in three patients: one case with severe hypotension and two cases with chest pain that was relieved with sublingual nitroglycerin. One patient died the day after stress MPI for reasons considered unrelated to regadenoson.
CONCLUSION: Regadenoson for MPI is easy to use with a high frequency of AEs, which are generally mild in severity, transient, and resolve spontaneously.

PMID: 26956081 [PubMed - indexed for MEDLINE]

Medication Errors: A Case-Based Review.

AACN Adv Crit Care. 2016 Feb;27(1):5-11

Authors: Pop M, Finocchi M

PMID: 26909446 [PubMed - indexed for MEDLINE]

Duvoglustat HCl Increases Systemic and Tissue Exposure of Active Acid α-Glucosidase in Pompe Patients Co-administered with Alglucosidase α.

Mol Ther. 2017 Mar 21;:

Authors: Kishnani P, Tarnopolsky M, Roberts M, Sivakumar K, Dasouki M, Dimachkie MM, Finanger E, Goker-Alpan O, Guter KA, Mozaffar T, Pervaiz MA, Laforet P, Levine T, Adera M, Lazauskas R, Sitaraman S, Khanna R, Benjamin E, Feng J, Flanagan JJ, Barth J, Barlow C, Lockhart DJ, Valenzano KJ, Boudes P, Johnson FK, Byrne B

Abstract
Duvoglustat HCl (AT2220, 1-deoxynojirimycin) is an investigational pharmacological chaperone for the treatment of acid α-glucosidase (GAA) deficiency, which leads to the lysosomal storage disorder Pompe disease, which is characterized by progressive accumulation of lysosomal glycogen primarily in heart and skeletal muscles. The current standard of care is enzyme replacement therapy with recombinant human GAA (alglucosidase alfa [AA], Genzyme). Based on preclinical data, oral co-administration of duvoglustat HCl with AA increases exposure of active levels in plasma and skeletal muscles, leading to greater substrate reduction in muscle. This phase 2a study consisted of an open-label, fixed-treatment sequence that evaluated the effect of single oral doses of 50 mg, 100 mg, 250 mg, or 600 mg duvoglustat HCl on the pharmacokinetics and tissue levels of intravenously infused AA (20 mg/kg) in Pompe patients. AA alone resulted in increases in total GAA activity and protein in plasma compared to baseline. Following co-administration with duvoglustat HCl, total GAA activity and protein in plasma were further increased 1.2- to 2.8-fold compared to AA alone in all 25 Pompe patients; importantly, muscle GAA activity was increased for all co-administration treatments from day 3 biopsy specimens. No duvoglustat-related adverse events or drug-related tolerability issues were identified.

PMID: 28341561 [PubMed - as supplied by publisher]

Does sevoflurane add to outpatient procedural sedation in children? A randomised clinical trial.

BMC Pediatr. 2017 Mar 24;17(1):86

Authors: Gomes HS, Gomes HS, Sado-Filho J, Costa LR, Costa PS

Abstract
BACKGROUND: There is little evidence concerning the effect of sevoflurane in outpatient procedural sedation, especially in children. We hypothesised that the addition of sevoflurane to a sedation regimen improves children's behaviour with minimal adverse events.
METHODS: This is a randomised, triple-blind clinical trial conducted on an outpatient basis. Participants were 27 healthy children aged 4 to 6 years, who previously refused dental treatment with non-pharmacologic methods. All participants received oral midazolam (0.5 mg/kg, maximum 20 mg) and oral ketamine (3 mg/kg, maximum 50 mg) and, in addition: Group MK - 100% oxygen; Group MKS - inhalational sevoflurane at a sedative dose (final expired concentration between 0.3 and 0.4%). Dental appointments were video recorded for assessment of the children's sleep patterns, crying, movements, and overall behaviour during the procedure with the Houpt scale. Intra- and post-operative adverse events were systematically reported. Data were analysed by bivariate analyses in the IBM SPSS v. 19, at a significance level of 5%.
RESULTS: MK (n = 13) and MKS (n = 14) did not differ regarding the Houpt scores (P > 0.05), but 53.8% of children in the MK group showed hysterical and continuous crying at the time of the local anaesthesia injection, compared to 7.1% of children in the MKS group (P = 0.01; phi = 0.5). There was a trend toward less crying and movement over time during the dental appointment in the MKS group (P = 0.48). Minor adverse events were observed in 10 MK children and 4 MKS children (P = 0.01).
CONCLUSIONS: The addition of sevoflurane to oral midazolam-ketamine improved the children's crying behaviour during local anaesthetic administration, and did not increase the occurrence of adverse events.
TRIAL REGISTRATION: Clinical Trials NCT02284204 . Registered 5 October 2014.

PMID: 28340572 [PubMed - in process]

In vitro testing of basal cytotoxicity: Establishment of an adverse outcome pathway from chemical insult to cell death.

Toxicol In Vitro. 2017 Mar;39:104-110

Authors: Vinken M, Blaauboer BJ

Abstract
In this paper, an in vitro basal cytotoxicity testing strategy is described for new chemical entities that lack any pre-existing information on potential toxicity. Special attention is paid to the selection of the cellular system, cytotoxicity assay and exposure conditions. This approach is based on a newly proposed generic adverse outcome pathway from chemical insult to cell death that consists of 3 steps, including initial cell injury, mitochondrial dysfunction and cell demise. The suggested strategy to consider in vitro basal cytotoxicity as a first step in evaluating the toxicity of new chemical entities can be placed in a tiered strategy that could be continued by evaluating more specific types of toxicity.

PMID: 27939612 [PubMed - indexed for MEDLINE]

Development of the Virtual Physical Assessment Learning Material That Allows the Learners to Check Drug Efficacy and Early Detection of Adverse Effects through Virtual Experience.

Yakugaku Zasshi. 2016;136(10):1439-1444

Authors: Tokunaga J, Takamura N, Kourogi Y, Imada M, Kozasa A, Komori K, Ono C, Nishimura A, Ogata K, Setoguchi N, Matsuoka T, Kai M, Sato K, Arimori K

Abstract
 We utilized the information and communication technology to develop the physical assessment (PA) learning materials in the virtual experience type. This learning material consists of two parts which include case learning and basic learning. We created example scenarios about various conditions that a pharmacist may experience in medical scenes such as in a hospital ward, community pharmacy, home, and drugstore. Illustrations of a virtual patient's avatar before and after taking the medicines were incorporated in the learning materials. The virtual training includes a stethoscope that was used in examining sounds (heart, pulmonary and bowel sounds) that served as evidences in the confirmation of drug efficacy and its possible adverse effects. In addition, we included the images of each body part, the 24 format question items, the palpation (rate and rhythm) of the radial artery, brachial artery and pedal artery, the clinical data obtained from several medical equipment, the pupillary reflex, and the urine dipstick test. This way, learners are able to experience PA with reference to the subjective and objective data from patient reception and questions. The virtual patient's avatar displayed on the monitor features auscultatory sounds on the stethoscope. It also features clinical data obtained from other medical equipment that can give the learners an interactive way of learning about various medical conditions. For evaluation, we gave out questionnaires on the virtual PA to pharmacy students. As a result, a high evaluation was reflected in terms of the degree of usefulness for both case learning and basic learning.

PMID: 27725393 [PubMed - indexed for MEDLINE]

Recommendations to improve adverse event reporting in clinical trial publications: a joint pharmaceutical industry/journal editor perspective.

BMJ. 2016 Oct 03;355:i5078

Authors: Lineberry N, Berlin JA, Mansi B, Glasser S, Berkwits M, Klem C, Bhattacharya A, Citrome L, Enck R, Fletcher J, Haller D, Chen TT, Laine C

PMID: 27697753 [PubMed - indexed for MEDLINE]

History repeats itself: the family medication history and pharmacogenomics.

Pharmacogenomics. 2016 05;17(7):669-78

Authors: Smith TR, Kearney E, Hulick PJ, Kisor DF

Abstract
Related to many drug gene-product interactions, application of pharmacogenomics can lead to improved medication efficacy while decreasing or avoiding adverse drug reactions. However, utilizing pharmacogenomics without other information does not allow for optimal medication therapy. Currently, there is a lack of documentation of family medication history, in other words, inefficacy and adverse reactions across family members throughout generations. The family medication history can serve as an impetus for pharmacogenomic testing to explain lack of medication efficacy or an adverse drug reaction and pre-emptive testing can drive recognition and documentation of medication response in family members. We propose combining the family medication history via pedigree construction with pharmacogenomics to further optimize medication therapy. We encourage clinicians to combine family medication history with pharmacogenomics.

PMID: 27143300 [PubMed - indexed for MEDLINE]

Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity.

Int Immunopharmacol. 2016 Jul;36:1-8

Authors: Chen Q, Peng H, Dong L, Chen L, Ma X, Peng Y, Dai S, Liu Q

Abstract
The nephrotoxicity of cisplatin (cis-DDP) limits its general clinical applications. Lentinan (LNT), a dextran extracted from the mushroom Lentinula edodes, has been shown to have multiple pharmacological activities. The primary objective of the current study was to determine whether and how LNT alleviates cis-DDP- induced cytotoxicity in HK-2 cells and nephrotoxicity in mice. LNT did not interfere with cisplatin's anti-tumour efficacy in vitro and functioned cooperatively with cis-DDP to inhibit activity in HeLa and A549 tumour cells. LNT alleviated the cis-DDP-induced decrease in HK-2 cell viability, caspase-3 activation and cleavage of the DNA repair enzyme PARP, decreased HK-2 cell apoptosis and inhibited reactive oxygen species (ROS) accumulation in HK-2 cells. The inhibitor of ROS (N-acetyl-L-cysteine, NAC) could decreased the apoptosis of HK-2 cell. In addition, LNT significantly prevented cis-DDP-induced kidney injury in vivo. LNT itself could not eliminate ROS levels in vitro. Further studies demonstrated that LNT induced NF-E2 p45-related factor 2 (Nrf2) protein and mRNA expression in a time- and dose-dependent manner. LNT promoted Nrf2 translocation to the nucleus and binding to the antioxidant-response element (ARE) sequence and induced the transcription and translation of heme oxygenase 1 (HO-1), aldo-keto reductases 1C1 and 1C2 (AKR1C), and NADP(H):quinone oxidoreductase 1 (NQO1). Finally, we used hNrf2 siRNA and an Nrf2 agonist (tBHQ) to inhibit or enhance Nrf2 expression. The results demonstrated that the LNT-mediated alleviation of cis-DDP-induced nephrotoxicity was achieved by preventing the accumulation of ROS in a manner that depended on the activation of the Nrf2-ARE signalling pathway.

PMID: 27093515 [PubMed - indexed for MEDLINE]

Health care cost associated with the use of enzyme-inducing and non-enzyme-active antiepileptic drugs in the UK: a long-term retrospective matched cohort study.

BMC Neurol. 2017 Mar 23;17(1):59

Authors: Borghs S, Thieffry S, Noack-Rink M, Dedeken P, Hong LS, Byram L, Logan J, Chan J, Kiri V

Abstract
BACKGROUND: Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years.
METHODS: Patients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010. Propensity score matching reduced confounding factors between cohorts. Patients were followed until cohort treatment failure or data cut-off. The primary outcome was the median standardized monthly direct health care cost during follow-up in 2014 £GBP, calculated using published reference costs and compared using a Mann-Whitney U test.
RESULTS: The unmatched EIAED cohort (n = 2752) was older (54 vs 46 years), more likely to be male, had more comorbidities, and higher health care resource use/cost during the 1-year pre-index period (median £3014 vs £2516) than the nEAAED cohort (n = 2,137). The most common index EIAED and nEAAED were carbamazepine (63.3%) and lamotrigine (58.0%), respectively. After matching, cohorts had similar features (n = 951 each). Over up to 12 years of follow-up, the median standardized monthly direct health care cost was £229 for the EIAED and £188 for the nEAAED cohorts (p = 0.0091). The median cost was higher for the EIAED cohort in every year of follow-up. In the two cohorts, 25.1% and 20.1% of total mean cost during follow-up was epilepsy-related, with approximately 4.6% and 3.0% for AED acquisition, respectively. The median time to cohort treatment failure was shorter in the matched EIAED cohort (468 vs 1194 days).
CONCLUSIONS: Patients in the UK who initiated epilepsy therapy with an EIAED appeared to be at higher risk of complications associated with enzyme induction. In long-term matched cohort analyses, the median total direct health care cost associated with EIAED therapy was higher than with nEAAEDs. Changing current treatment practices could potentially improve patient outcomes and reduce costs.

PMID: 28335764 [PubMed - in process]