Related Articles

Use of a trigger tool to detect adverse drug reactions in an emergency department.

BMC Pharmacol Toxicol. 2017 Nov 15;18(1):71

Authors: de Almeida SM, Romualdo A, de Abreu Ferraresi A, Zelezoglo GR, Marra AR, Edmond MB

Abstract
BACKGROUND: Although there are systems for reporting adverse drug reactions (ADR), these safety events remain under reported. The low-cost, low-tech trigger tool method is based on the detection of events through clues, and it seems to increase the detection of adverse events compared to traditional methodologies. This study seeks to estimate the prevalence of adverse reactions to drugs in patients seeking care in the emergency department.
METHODS: Retrospective study from January to December, 2014, applying the Institute for Healthcare Improvement (IHI) trigger tool methodology for patients treated at the emergency room of a tertiary care hospital.
RESULTS: The estimated prevalence of adverse reactions in patients presenting to the emergency department was 2.3% [CI95 1.3% to 3.3%]; 28.6% of cases required hospitalization at an average cost of US$ 5698.44. The most common triggers were hydrocortisone (57% of the cases), diphenhydramine (14%) and fexofenadine (14%). Anti-infectives (19%), cardiovascular agents (14%), and musculoskeletal drugs (14%) were the most common causes of adverse reactions. According to the Naranjo Scale, 71% were classified as possible and 29% as probable. There was no association between adverse reactions and age and sex in the present study.
CONCLUSIONS: The use of the trigger tool to identify adverse reactions in the emergency department was possible to identify a prevalence of 2.3%. It showed to be a viable method that can provide a better understanding of adverse drug reactions in this patient population.

PMID: 29141696 [PubMed - indexed for MEDLINE]

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Surface-modified mucoadhesive microgels as a controlled release system for miconazole nitrate to improve localized treatment of vulvovaginal candidiasis.

Eur J Pharm Sci. 2018 Jan 01;111:358-375

Authors: Kenechukwu FC, Attama AA, Ibezim EC, Nnamani PO, Umeyor CE, Uronnachi EM, Gugu TH, Momoh MA, Ofokansi KC, Akpa PA

Abstract
The use of conventional vaginal formulations of miconazole nitrate (MN) in the treatment of deep-seated VVC (vulvovaginal candidiasis) is limited by poor penetration capacity and low solubility of MN, short residence time and irritation at the application site. Surface-modified mucoadhesive microgels were developed to minimize local irritation, enhance penetration capacity and solubility and prolong localized vaginal delivery of MN for effective treatment of deep-seated VVC. Solid lipid microparticles (SLMs) were prepared from matrices consisting of hydrogenated palm oil (Softisan® 154, SF) and super-refined sunseed oil (SO) with or without polyethylene glycol (PEG)-4000, characterized for physicochemical performance and used to prepare mucoadhesive microgels (MMs) encapsulating MN, employing Polycarbophil as bioadhesive polymer. The MMs were evaluated for physicochemical performance and in vitro drug release in simulated vaginal fluid (pH=4.2), whereas mucoadhesive, rheological and stability tests, anticandidal efficacy in immunosuppressed estrogen-dependent female rats and vaginal tolerance test in rabbits were performed with optimized formulation. The amorphicity of 1:9 phytolipid blend (SO:SF) was increased in the presence of PEG-4000. The physicochemical properties of the SLMs and MMs indicated their suitability for vaginal drug delivery. Overall, MN-loaded PEGylated MMs exhibited significantly (p<0.05) more prolonged drug release than non-PEGylated MMs. Additionally, optimized PEGylated MMs was stable at 40±2°C over a period of 6months, viscoelastic, mucoadhesive, non-sensitizing, histopathologically safe and gave remarkably (p<0.05) higher reduction in Candida albicans load (86.06%) than Daktarin® (75.0%) and MN-loaded polymeric-hydrogel (47.74%) in treated rats in 12days. Thus, PEGylated MMs is promising for effective and convenient treatment of VVC.

PMID: 28986195 [PubMed - indexed for MEDLINE]

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Pharmacovigilance in Israel - tools, processes, and actions.

Isr J Health Policy Res. 2017 Aug 01;6(1):29

Authors: Schwartzberg E, Berkovitch M, Dil Nahlieli D, Nathan J, Gorelik E

Abstract
BACKGROUND: Due to the limited safety data available at the time that a new medication is first marketed, it is essential to continue the collection and monitoring of safety data about adverse drug reactions (ADRs) during the medication's life cycle. This activity, known as pharmacovigilance (PV), is performed worldwide by the pharmaceutical industry as well as by regulatory agencies. In 2012, the Israeli Ministry of Health (MOH) established a Pharmacovigilance and Drug Information Department. The Department is tasked with identifying, monitoring, and initiating activities aimed at minimizing risks associated with medication utilization. To enable this, the MOH has devised procedures for PV and promoted extensive legislation in this area that require marketing authorization holders (MAHs) and medical institutions in Israel to report ADRs and new safety information to the MOH. A computerized database was created to support the reporting process. The objective of this article is to characterize the PV tools and activities implemented in Israel.
METHODS: Since September 2014, The Israeli Pharmacovigilance and Drug Information Department receives ICSRs at a central computerized database developed for this purpose. The data were analyzed by Department personnel and ICSRs were characterized according to their seriousness, source, categories of drugs involved, and the reporting format. Additionally, the Department reviewed signals detected from ADR reports and from other sources and assessed the resulting regulatory actions.
RESULTS: An analysis of the Individual Case Safety Reports (ICSRs) submitted to the MOH's ADRs central database reveals that during the review period, a total of 16,409 ICSRs were received by the Department and 850 signals were identified, resulting in the following PV activities: inquiry and enhanced follow-up (430, 50.6%), prescriber's and patient's leaflets updates (204, 24%), recall of products/batches (6, 0.7%), alerts for health care professionals (63, 7.4%). Eighty five (10%) of the signals required a comprehensive investigation involving external specialist and 1 (0.1%) resulted in initiation of epidemiologic study. Additionally, in 2015 the Department incorporated comprehensive framework for risk minimization of marketed medicinal products, also known as risk management plans (RMPs).
CONCLUSIONS: As practiced by other health authorities, the Israeli MOH effectively implemented various PV tools to ensure the safety of the Israeli health consumer.

PMID: 28760141 [PubMed - indexed for MEDLINE]

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A Multicentre Study on the Efficacy, Safety and Pharmacokinetics of IqYmune®, a Highly Purified 10% Liquid Intravenous Immunoglobulin, in Patients with Primary Immune Deficiency.

J Clin Immunol. 2017 Aug;37(6):539-547

Authors: Krivan G, Chernyshova L, Kostyuchenko L, Lange A, Nyul Z, Derfalvi B, Musial J, Bellon A, Kappler M, Sadoun A, Bernatowska E

Abstract
This multicentre, open-label, prospective, single-arm study was designed to evaluate the efficacy, pharmacokinetics, and safety of IqYmune®, a highly purified 10% polyvalent immunoglobulin preparation for intravenous administration in patients with primary immunodeficiency. IqYmune® was administered to 62 patients (aged 2-61 years) with X-linked agammaglobulinemia or common variable immune deficiency at a dose from 0.22 to 0.97 g/kg every 3 to 4 weeks for 12 months with an infusion rate up to 8 mL/kg/h. A pharmacokinetic study was performed at steady state between the 8th and the 9th infusion. A single case of serious bacterial infection was observed, leading to an annualized rate of serious bacterial infections/patient (primary endpoint) of 0.017 (98% CI: 0.000, 0.115). Overall, 228 infections were reported, most frequently bronchitis, chronic sinusitis, nasopharyngitis and upper respiratory tract infection. The mean annualized rate of infections was 3.79/patient. A lower risk of infections was associated with an IgG trough level > 8 g/L (p = 0.01). The mean annualized durations of absence from work or school and of hospitalization due to infections were 1.01 and 0.89 days/patient, respectively. The mean serum IgG trough level before the 6th infusion was 7.73 g/L after a mean dose of IqYmune® of 0.57 g/kg. The pharmacokinetic profile of IqYmune® was consistent with that of other intravenous immunoglobulins. Overall, 15.5% of infusions were associated with an adverse event occurring within 72 h post infusion. Headache was the most common adverse event. In conclusion, IqYmune® was shown to be effective and well tolerated in patients with primary immunodeficiency.

PMID: 28711959 [PubMed - indexed for MEDLINE]

Related Articles

Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.

HIV Med. 2018 Jan;19(1):65-71

Authors: Pett SL, Amin J, Horban A, Andrade-Villanueva J, Losso M, Porteiro N, Madero JS, Belloso W, Tu E, Silk D, Kelleher A, Harrigan R, Clark A, Sugiura W, Wolff M, Gill J, Gatell J, Clarke A, Ruxrungtham K, Prazuck T, Kaiser R, Woolley I, Alberto Arnaiz J, Cooper D, Rockstroh JK, Mallon P, Emery S, MARCH study group

Abstract
OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding.
METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints.
RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms.
CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

PMID: 28703491 [PubMed - indexed for MEDLINE]

Funding Opportunity RFA-DE-19-004 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications to develop physiologically relevant models of amelogenesis that are robust and validated so that they can advance studies of healthy and diseased human conditions involving teeth. The objectives of this FOA are two-fold: 1) generate new and improved models that closely mimic physiological enamel development and maturation to empower studies of amelogenesis, and 2) validate those models to ensure they are robust and accurately reflect human physiology and pathology. These tandem objectives will be accomplished with an Exploratory/Developmental Phased Award Cooperative Agreement (UG3/UH3) mechanism, where the UG3 developmental phase is initiated and carried out through a milestone-driven process which will then be assessed to determine if advancement to the UH3 phase providing subsequent support to further advance the UG3 outcomes will be granted . It is expected this FOA will enhance the capability of resources to serve biomedical research and accelerate understanding of multiscale processes of enamel formation to inform strategies to mitigate diseases affecting enamel and associated structures.

Notice NOT-HL-18-640 from the NIH Guide for Grants and Contracts

Notice NOT-HD-18-014 from the NIH Guide for Grants and Contracts

Notice NOT-OD-18-203 from the NIH Guide for Grants and Contracts

Notice NOT-OD-18-204 from the NIH Guide for Grants and Contracts

Notice NOT-HL-18-641 from the NIH Guide for Grants and Contracts

Notice NOT-DA-18-024 from the NIH Guide for Grants and Contracts

Notice NOT-HL-18-642 from the NIH Guide for Grants and Contracts

Notice NOT-HS-18-011 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-18-853 from the NIH Guide for Grants and Contracts. The purpose of this funding opportunity announcement (FOA) is to support research to elucidate the chemical features of non-native molecules that cross the blood-testis and/or blood-epidydimal barriers.

Notice NOT-OD-18-208 from the NIH Guide for Grants and Contracts

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