Documentation of penicillin adverse drug reactions in electronic health records: inconsistent use of allergy and intolerance labels.

Intern Med J. 2017 Nov;47(11):1292-1297

Authors: Inglis JM, Caughey GE, Smith W, Shakib S

Abstract
BACKGROUND: The majority of patients with penicillin allergy labels tolerate penicillins. Inappropriate avoidance of penicillin is associated with increased hospitalisation, infections and healthcare costs.
AIMS: To examine the documentation of penicillin adverse drug reactions (ADR) in a large-scale hospital-based electronic health record.
METHODS: Penicillin ADR were extracted from 96 708 patient records in the Enterprise Patient Administration System in South Australia. Expert criteria were used to determine consistency of ADR entry and suitability for further evaluation.
RESULTS: Of 43 011 unique ADR reports, there were 5023 ADR to penicillins with most being entered as allergy (n = 4773, 95.0%) rather than intolerance (n = 250, 5.0%). A significant proportion did not include a reaction description (n = 1052, 20.9%). Using pre-set criteria, 10.1% of reports entered as allergy had a reaction description that was consistent with intolerance and 31.0% of the entered intolerances had descriptions consistent with allergy. Virtually all ADR (n = 4979, 99.1%) were appropriate for further evaluation by history taking or immunological testing and half (50.7%, n = 2549) had documented reactions suggesting low-risk of penicillin allergy.
CONCLUSION: The frequency of penicillin allergy label in this data set is consistent with the known overdiagnosis of penicillin allergy in the hospital population. ADR documentation was poor with incomplete entries and inconsistent categorisation. The concepts of allergy and intolerance for ADR classification, whilst mechanistically valid, may not be useful at the point of ADR entry by generalist clinicians. Systematic evaluation of reported ADR is needed to improve the quality of information for future prescribers.

PMID: 28742226 [PubMed - indexed for MEDLINE]

[Adverse events related to medication in hospitals from the Valencian Community. EPIDEA Study 2005-2013].

Rev Esp Quimioter. 2017 Oct;30(5):319-326

Authors: Mollar-Maseres JB, Aranaz-Andrés JM, Martin-Moreno JM, Miralles-Bueno JJ, Requena-Puche J, Martínez-Morel HR, Luján-Tolosa MM

Abstract
OBJECTIVE: To determine the prevalence of Adverse Events related to Medication (AEM) in hospitals of the Valencian Community in the 2005-2013 study period, and to describe the associated risk factors and their impact.
METHODS: This study is based on data and methodology of the Study of Prevalence of Adverse Events in hospitals (EPIDEA), since its inception in 2005 until 2013. AEM produced in each year were analyzed.
RESULTS: We identified 344 AEM that occurred in 337 patients, among 35,103 patients studied, giving a prevalence of patients with AEM of 0.96% (IC95% 0.89-1.07). The most prevalent intrinsic risk factors for AEM were hypertension, diabetes and cancer. The most prevalent extrinsic risk factors were peripheral venous catheter, urinary catheter and central venous catheter. Therapeutic groups most frequently involved were systemic antibiotics, cardiovascular drugs and antineoplastics. The 61.17% of AEM was classified as moderate, followed by 27.18% as mild and 11.65% as severe. The 33.99% of EAM caused increase of the patient's stay and 39.90% of EAM caused the re-entry of patient. The 58.5% of AEM were avoidable. Mild AEM were avoidable in 46.3%, moderate AEM were avoidable in 60.3% and severe AEM were in 75% (p = 0.013).
CONCLUSIONS: The prevalence of patients with AEM in hospitals of the Community of Valencia for the period 2005- 2013 was 0.96%. More than half of AEM were preventable, and preventability increases significantly with the severity of the event.

PMID: 28722391 [PubMed - indexed for MEDLINE]

Bayesian adaptive dose-escalation designs for simultaneously estimating the optimal and maximum safe dose based on safety and efficacy.

Pharm Stat. 2017 Nov;16(6):396-413

Authors: Yeung WY, Reigner B, Beyer U, Diack C, Sabanés Bové D, Palermo G, Jaki T

Abstract
The main purpose of dose-escalation trials is to identify the dose(s) that is/are safe and efficacious for further investigations in later studies. In this paper, we introduce dose-escalation designs that incorporate both the dose-limiting events and dose-limiting toxicities (DLTs) and indicative responses of efficacy into the procedure. A flexible nonparametric model is used for modelling the continuous efficacy responses while a logistic model is used for the binary DLTs. Escalation decisions are based on the combination of the probabilities of DLTs and expected efficacy through a gain function. On the basis of this setup, we then introduce 2 types of Bayesian adaptive dose-escalation strategies. The first type of procedures, called "single objective," aims to identify and recommend a single dose, either the maximum tolerated dose, the highest dose that is considered as safe, or the optimal dose, a safe dose that gives optimum benefit risk. The second type, called "dual objective," aims to jointly estimate both the maximum tolerated dose and the optimal dose accurately. The recommended doses obtained under these dose-escalation procedures provide information about the safety and efficacy profile of the novel drug to facilitate later studies. We evaluate different strategies via simulations based on an example constructed from a real trial on patients with type 2 diabetes, and the use of stopping rules is assessed. We find that the nonparametric model estimates the efficacy responses well for different underlying true shapes. The dual-objective designs give better results in terms of identifying the 2 real target doses compared to the single-objective designs.

PMID: 28691311 [PubMed - indexed for MEDLINE]

Effect of food on the pharmacokinetic characteristics of a single oral dose of LCB01-0371, a novel oxazolidinone antibiotic.

Drug Des Devel Ther. 2018;12:1707-1714

Authors: Sunwoo J, Kim YK, Choi Y, Yu KS, Nam H, Cho YL, Yoon S, Chung JY

Abstract
Background: LCB01-0371 is a novel oxazolidinone antibiotic that blocks protein production by binding to bacterial 23S ribosomes. This antibiotic is active against Gram-positive bacteria. This study aimed to evaluate the effect of food on the pharmacokinetics (PKs) of LCB01-0371 and evaluate its safety profile.
Subjects and methods: A randomized, open-label, two-way crossover study was performed in 18 healthy Korean male subjects. All subjects received a single oral 800 mg dose of LCB01-0371 in each period under fed or fasting condition with a 7-day washout in between. The fed condition was defined as consumption of a meal of 800-1,000 kcal containinĝ50% of fat content. Serial blood samples were collected over 24 h after dosing, and the PK parameters were calculated by noncompartment analysis. All available data of the subjects who received LCB01-0371 at least once were included in the safety data summaries.
Results: In the fed condition, both the maximum plasma concentration (Cmax) and the total systemic exposure (area under the plasma concentration-time curve from time zero to the last observed time point [AUClast]) decreased by ~33% and 10%, respectively. The time to reach Cmax was delayed by ~1.25 h in the fed condition, whereas the mean elimination half-life remained similar in both conditions. In the fed/fasting condition, the geometric mean ratios and 90% CI of the Cmax and AUClast were 0.666 (0.470-0.945) and 0.897 (0.761-1.057), respectively. There were no drug-related adverse events (AEs) or serious AEs.
Conclusion: Although the Tmax after a single oral 800 mg dose of LCB01-0371 was slightly delayed under the fed condition compared to the fasting condition, the total systemic exposure was similar under both conditions. Therefore, LCB01-0371 could be administered regardless of food intake.

PMID: 29928114 [PubMed - in process]

Ipragliflozin Add-on Therapy to a GLP-1 Receptor Agonist in Japanese Patients with Type 2 Diabetes (AGATE): A 52-Week Open-Label Study.

Diabetes Ther. 2018 Jun 20;:

Authors: Ishihara H, Yamaguchi S, Nakao I, Sakatani T

Abstract
INTRODUCTION: Few data are available regarding ipragliflozin treatment in combination with glucagon-like peptide-1 (GLP-1) receptor agonists. The aim of this study was to evaluate the efficacy and safety of ipragliflozin in combination with GLP-1 receptor agonists in Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM).
METHODS: This multicenter study (consisting of three periods: a 4-week washout period, a 6-week observation period, and a 52-week open-label treatment period) included patients aged ≥ 20 years who received a stable dose/regimen of a GLP-1 receptor agonist either solely or in combination therapy with a sulfonylurea for ≥ 6 weeks, with glycosylated hemoglobin (HbA1c) of ≥ 7.5% and a fasting plasma glucose (FPG) of ≥ 126 mg/dL. Ipragliflozin treatment was given at a fixed dose of 50 mg/day for 20 weeks, followed by 50 or 100 mg/day for 32 weeks. Changes from baseline in glycemic control and other parameters were examined; safety was also assessed.
RESULTS: The mean changes in HbA1c and body weight from baseline to end of treatment were - 0.92% and - 2.69 kg, respectively, in all ipragliflozin-treated patients (n = 103). Overall, sustained reductions from baseline were observed for HbA1c, FPG, self-monitored blood glucose, and body weight during the 52-week treatment. The dose increase of ipragliflozin to 100 mg/day resulted in better glycemic control and weight reduction for patients in whom the 50-mg dose was insufficient. Overall, 46.6% (48/103) of patients experienced drug-related adverse events. The most common drug-related treatment-emergent adverse events were pollakiuria (9.7%), hypoglycemia (8.7%), constipation (6.8%), and thirst (5.8%).
CONCLUSION: Combined therapy with ipragliflozin and GLP-1 receptor agonists/sulfonylureas was significantly efficacious in reducing glycemic parameters in patients with T2DM with inadequate glycemic control, and no major safety concerns were identified. The results from this study suggest that ipragliflozin can be recommended as a well-tolerated and effective add-on therapy to a GLP-1 receptor agonist for the treatment of T2DM.
TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT02291874).
FUNDING: Astellas Pharma Inc., Tokyo, Japan.

PMID: 29926400 [PubMed - as supplied by publisher]

Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial.

Lancet HIV. 2018 Jun 15;:

Authors: Daar ES, DeJesus E, Ruane P, Crofoot G, Oguchi G, Creticos C, Rockstroh JK, Molina JM, Koenig E, Liu YP, Custodio J, Andreatta K, Graham H, Cheng A, Martin H, Quirk E

Abstract
BACKGROUND: Switching from therapy based on a boosted protease inhibitor to bictegravir, emtricitabine, and tenofovir alafenamide could avoid drug interactions and unwanted side-effects in virologically suppressed adults with HIV-1 infection, while maintaining a high barrier to resistance and providing a simplified once-daily, single-tablet regimen. Here, we report 48 week results of a phase 3 study investigating this switch.
METHODS: In this multicentre, randomised, open-label, active-controlled, non-inferiority, phase 3 trial, adults with HIV-1 infection were enrolled at 121 outpatient centres in ten countries. Eligible participants were aged 18 years or older, had an estimated glomerular filtration rate of 50 mL per min or higher, had been virologically suppressed (plasma HIV-1 RNA <50 copies per mL) for 6 months or more before screening, and were on a regimen consisting of boosted atazanavir or darunavir plus either emtricitabine and tenofovir disoproxil fumarate or abacavir and lamivudine. We randomly assigned participants (1:1), using a computer-generated randomisation sequence, to switch to co-formulated once-daily bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg), herein known as the bictegravir group, or to remain on their baseline boosted protease inhibitor regimen, herein known as the boosted protease inhibitor group, for 48 weeks. Randomisation was stratified by use of tenofovir disoproxil fumarate or abacavir at screening. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or higher at week 48 (by US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 4%. Efficacy and safety analyses included all participants who received at least one dose of study drug. This study is ongoing but not actively recruiting patients and is registered with ClinicalTrials.gov, number NCT02603107.
FINDINGS: Between Dec 2, 2015, and July 15, 2016, 578 participants were randomly assigned and 577 were treated (290 in the bictegravir group and 287 in the boosted protease inhibitor group). At week 48, five participants (2%) in the bictegravir group and five (2%) in the boosted protease inhibitor group had plasma HIV-1 RNA of 50 copies per mL or higher (difference 0·0%, 95·002% CI -2·5 to 2·5), thus switching to the bictegravir regimen was non-inferior to continued boosted protease inhibitor therapy. The overall incidence and severity of adverse events was similar between groups, although headache occurred more frequently in the bictegravir group than in the boosted protease inhibitor group. 233 (80%) participants in the bictegravir group and 226 (79%) in the boosted protease inhibitor group had an adverse event. Only two (1%) participants in the bictegravir group and one (<1%) in the boosted protease inhibitor group discontinued treatment because of adverse events. 54 participants (19%) in the bictegravir group had drug-related adverse events compared with six (2%) in the protease inhibitor group.
INTERPRETATION: Fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide might be a safe and efficacious alternative to continued boosted protease inhibitor therapy in adults with HIV-1 infection.
FUNDING: Gilead Sciences.

PMID: 29925490 [PubMed - as supplied by publisher]

Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab.

Int Rev Immunol. 2017 Nov 02;36(6):352-359

Authors: Christou EAA, Giardino G, Worth A, Ladomenou F

Abstract
Rituximab (RTX) is a monoclonal antibody against CD20, commonly used in the treatment of hematological malignancies and autoimmune diseases. The use of RTX is related to the development of hypogammaglobulinemia and infections. Aim of this review is to summarize the evidence supporting the association of specific risk factors with the development of hypogammaglobulinemia and infections post-RTX. Immunological complications are more common in patients with malignant diseases as compared to non-malignant diseases. Moreover, the use of more than one dose of RTX, maintenance regimens, low pre-treatment basal immunoglobulin levels and the association with Mycophenolate and purine analogues represent risk factors for the development of hypogammaglobulinemia. The number of RTX courses, the evidence of low IgG levels for more than 6 months, the use of G-CSF, the occurrence of chronic lung disease, cardiac insufficiency, extra-articular involvement in patients with rheumatoid arthritis, low levels of IgG and older age have been correlated with a higher risk of infections. Even though the heterogeneity of the studies in terms of study population age and underlying disease, RTX schedules as well as differences in pre-treatment or concomitant therapy doesn't allow drawing definitive conclusions, the study of the literature highlight the association of specific risk factors with the occurrence of hypogammaglobulinemia and/or infections. A long term randomized controlled clinical trial could be useful to define a personalized evidence-based risk management plan for patients treated with RTX.

PMID: 28800262 [PubMed - indexed for MEDLINE]

An Economic Analysis of a Peanut Oral Immunotherapy Study in Children.

J Allergy Clin Immunol Pract. 2017 Nov - Dec;5(6):1707-1716

Authors: Shaker MS

Abstract
BACKGROUND: Peanut oral immunotherapy (POIT) decreases the probability of accidental recurrent systemic reactions but reactions from the therapy itself are frequent.
OBJECTIVE: The purpose of this economic analysis was to characterize the potential cost-effectiveness of POIT.
METHODS: Cohort simulations were used to evaluate the effect of POIT for children with peanut allergy. A POIT with probiotic was used in the base-case simulation and long-term survival was modeled using age-adjusted mortality together with the risk of food allergy-associated mortality.
RESULTS: The incremental POIT cost-effectiveness ratio was $2142 per quality-adjusted life-year. A mean number of 12.3 (95% CI, 12.0-12.5) and 2.0 (95% CI, 1.9-2.1) allergic reactions occurred in the POIT and avoidance groups over 20 years of simulation, with 2.3 (95% CI, 2.2-2.3) episodes of anaphylaxis treated with intramuscular epinephrine per subject in the POIT group and 1.1 (95% CI, 1.0-1.2) episodes per subject in the avoidance group. In sensitivity analyses, POIT was associated with lower rates of anaphylaxis than strict avoidance when the annual rate of accidental allergic reactions in the peanut avoidance group exceeded 25%, the annual rate of anaphylaxis in the POIT group dropped below 6%, or the probability of sustained unresponsiveness after 4 years of POIT was 68% or greater.
CONCLUSIONS: POIT may be cost-effective in a long-term economic model. However, treated patients may experience a greater rate of peanut-associated allergic reactions and anaphylaxis. The analysis was sensitive to rates of accidental allergic reactions, therapy-associated adverse events, and likelihood of therapy-induced tolerance.

PMID: 28606784 [PubMed - indexed for MEDLINE]

"Treating Through" Decision and Follow-up in Antibiotic Therapy-Associated Exanthemas.

J Allergy Clin Immunol Pract. 2017 Nov - Dec;5(6):1650-1656

Authors: Trautmann A, Benoit S, Goebeler M, Stoevesandt J

Abstract
BACKGROUND: Immediate discontinuation or replacement of suspected drugs is considered standard medical care in acute exanthematous skin reactions. In the treatment of bacterial infections, structurally different alternative antibiotics, however, are commonly second choice options due to a suboptimal antimicrobial activity or an unfavorable side effect profile. Nonetheless, "treating through," the continuation of antibiotic treatment despite an objective exanthema, is practiced only rarely.
OBJECTIVE: We aimed to assess whether "treating through" is an option for patients with severe bacterial soft tissue infections (severe cellulitis) who experience maculopapular exanthema (MPE) during antibiotic therapy.
METHODS: We retrospectively reviewed clinical data from 18 patients who developed MPE within a few days after initiation of intravenous antibiotic treatment. A decision to "treat through" was made when the suspected antibiotics (β-lactams, clindamycin, ciprofloxacin) were clinically effective and the benefits of continued treatment outweighed potential risks. Clinical and laboratory findings were closely monitored in an inpatient setting.
RESULTS: In 2 patients, a modification of antibiotic therapy was deemed necessary due to a significant increase of liver enzymes within 4 days after the initial decision to "treat through." Because of a progression of MPE under ongoing treatment with cefuroxime and clindamycin, clindamycin was discontinued in 1 patient. In another 3 patients, antibiotic treatment was modified because of insufficient improvement of the soft tissue infection. In the remaining 12 "treated through" cases, the skin symptoms improved despite unchanged continued antibiotic treatment, and relevant laboratory parameters remained within the normal range.
CONCLUSIONS: Careful risk-benefit assessment may enable the continuation of antibiotic therapy despite MPE, provided that patients are under close medical observation.

PMID: 28499779 [PubMed - indexed for MEDLINE]

Adverse Effects of Domperidone: Prolonged QuesT for Knowledge?

Dig Dis Sci. 2016 12;61(12):3384-3386

Authors: Bashashati M, Sarosiek I, Siddiqui T, McCallum RW

PMID: 27714509 [PubMed - indexed for MEDLINE]

18 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 2018/06/21

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.

18 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 2018/06/21

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.

Generalizability of clinical trials of advanced melanoma in the real-world, population-based setting.

Med Oncol. 2018 Jun 18;35(7):110

Authors: Sam D, Gresham G, Abdel-Rahman O, Cheung WY

Abstract
Results from novel therapeutics trials are not always generalizable to real-world patients. We aimed to determine the pattern in which trial findings are applied in a population-based setting of melanoma patients and consequent treatment outcomes. Patients with unresectable disease during 2011-2014 and referred to cancer centers in a large Canadian province were retrospectively reviewed. Based on eligibility criteria as described in registration trials of vemurafenib (Vem) and ipilimumab (Ipi), we classified patients into trial-eligible and ineligible and those treated and untreated with these agents. We identified 290 patients with known BRAF status for the Vem analysis and 212 patients previously treated with first-line agents for the Ipi analysis. For the Vem cohort, a total of 49 patients were considered trial-eligible, of whom 36 (73%) received treatment. For the Ipi cohort, there were 119 trial-eligible cases of whom 43 (36%) received therapy. Factors other than eligibility criteria most frequently associated with non-treatment in these cohorts included concerns regarding treatment harm and patient preferences. In multivariable analysis, overall survival was improved in Vem cohort patients considered trial-eligible and treated compared to those who were ineligible. Within the Ipi cohort, survival was improved in trial-eligible patients regardless of whether they received Ipi compared to ineligible patients. Real-world uptake of new melanoma treatments was suboptimal, and non-use in trial-eligible patients was frequent. Future clinical trials that are more pragmatically designed to include participants who better reflect the real-world population may facilitate increased uptake of novel therapeutics into routine clinical practice.

PMID: 29915956 [PubMed - in process]

Intra-articular injection of the anti-inflammatory compound LMWF-5A in adults with severe osteoarthritis: a double-blind prospective randomized controlled multi-center safety and efficacy trial.

Patient Saf Surg. 2018;12:11

Authors: Salottolo K, Cole B, Bar-Or D

Abstract
Background: There are limited efficacious treatment options for severe osteoarthritis of the knee (OAK). The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is in development to treat severe OAK. This study evaluated the safety and efficacy of LMWF-5A for the signs and symptoms of OAK.
Methods: This 12-week randomized, double-blind, controlled clinical trial was conducted at thirteen sites across the United States. Patients with symptomatic, severe OAK (Kellgren-Lawrence grade 4 disease) who were fully ambulatory and had no other conditions interfering with the study knee were randomized to a single 4 ml intra-articular injection of LMWF-5A or saline, randomized 6:1. The primary endpoint was Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) responder rate (%), examined with a one-sided exact binomial test compared to a clinically meaningful response rate of 30%. Efficacy of LMWF-5A was also evaluated as controlled responder (%), defined as 20% improvements in both pain and function, compared to historical saline control from three previous trials. Safety was examined as the incidence and severity of adverse events (AEs). This trial was registered (clinicaltrials.gov identifier: NCT03182686).
Results: In total, 168 patients were randomized; 144 subjects treated with LMWF-5A were analysed. Overall, 71% (95% CI: 63.4%-78.3%) of subjects treated with LMWF-5A met the OMERACT-OARSI responder criteria, exceeding the 30% threshold (p < 0.001). There were also significantly more responders at week 12 in the LMWF-5A arm than historical saline control (65% vs. 43%, p < 0.001). There were no drug-related serious AEs reported and no deaths or withdrawals due to adverse events.
Conclusion: LMWF-5A provides relief for the signs and symptoms of severe osteoarthritis, and may be an alternative therapeutic treatment option for patients with severe osteoarthritis of the knee.

PMID: 29910837 [PubMed]

South Korean geriatrics on Beers Criteria medications at risk of adverse drug events.

PLoS One. 2018;13(3):e0191376

Authors: Kim GJ, Lee KH, Kim JH

Abstract
BACKGROUND: The Beers Criteria released by the American Geriatrics Society includes a list of drugs to avoid in the geriatric population and is frequently used as a safety resource in geriatric pharmacotherapy.
OBJECTIVE: To evaluate the exposure of South Korean geriatrics to potentially inappropriate medications according to the Beers Criteria and the risk of adverse events from these medications.
METHODS: This study included medications recommended to be avoided in patients 65 years or older regardless of concomitant drug therapy or disease. The exposure of South Korean geriatrics to each of the study medications were examined using health claims data of 2011. The number of South Korean geriatrics at risk of experiencing adverse drug events from the study medications were estimated by multiplying the number of patients exposed to the medication in 2011 and the incident rate of the event obtained from literature sources.
RESULTS: This study examined 166,822 geriatrics for Beers Criteria medication exposure and adverse drug event risk. The most prevalent Beers Criteria medication prescribed in South Korean geriatrics >1 day was chlorpheniramine (53.9%) and the adverse drug event with the highest number of this geriatric population at risk of was amitriptyline related dry mouth (4.9%). The proportion of South Korean geriatrics on chronic Beers Criteria medications >1 day at risk of adverse drug events from these medications was significantly higher than in US geriatrics (0.005 vs. 0.001, 2-way ANOVA post hoc pairwise t-test P<0.0001).
CONCLUSIONS: In 2011, over half of South Korean geriatrics was exposed to medications recommended to be avoided in geriatrics and their adverse drug event risk warrants close monitoring of their occurrence.

PMID: 29543860 [PubMed - indexed for MEDLINE]

The key role of clinical and community health nurses in pharmacovigilance.

Eur J Clin Pharmacol. 2017 Nov;73(11):1379-1387

Authors: Bigi C, Bocci G

Abstract
PURPOSE: The reporting of suspected adverse drug reactions (ADRs) is starting to become routine to nurses. The aim of this review is to underline the role of clinical and community health nurses in pharmacovigilance and to promote their effective participation in ADR reporting in different countries and for patients of different ages.
METHODS: The PubMed, Scopus and ISI Web of Science databases were searched for research articles published between January 1985 and April 2017 using the search items "pharmacovigilance" AND "nurse;" "adverse drug reaction report" AND "nurse;" "community health nurse" AND "adverse drug reaction."
RESULTS: A total of 987 articles were identified using our search strategy, of which 180 articles remained over after the removal of duplicate articles. Of these 180 studies, upon full review we identified 24 which met the inclusion/exclusion criteria and included these in our review. ADR reports by clinical nurses in some countries are comparable in quality and number to those submitted by physicians or pharmacists. Data on ADRs reported by community nurses are currently not available. However, numerous publications emphasized the challenges faced by nurses in reporting ADRs and the need to include pharmacovigilance training in both clinical and community health nurse academic education.
CONCLUSIONS: Nurses are central actors in pharmacovigilance activities, particularly in identifying ADRs which remain outside the reach of other healthcare providers and in being fundamental to the preservation of the health of patients and of the entire community, with attention to the more vulnerable patients, such as children and the elderly.

PMID: 28770283 [PubMed - indexed for MEDLINE]

Drug-Induced Thrombophilic or Prothrombotic States: An Underestimated Clinical Problem That Involves Both Legal and Illegal Compounds.

Clin Appl Thromb Hemost. 2017 Oct;23(7):775-785

Authors: Girolami A, Cosi E, Tasinato V, Santarossa C, Ferrari S, Girolami B

Abstract
Vascular thrombosis, both arterial and venous, is a condition associated with significant morbidity and mortality. There are multiple risk factors for thrombosis, both congenital and acquired, and in the majority of cases, these risk factors are not modifiable. Over the past 2 decades, multiple drugs (both illegal and legal) have been associated with increased risk of thrombosis. However, due to limited scientific literature regarding the prothrombotic tendencies of these drugs, there is a concomitant limited understanding of the pathophysiology of drug-induced thrombosis. As drugs are one of the few modifiable risk factors for thrombosis, further study and dissemination of knowledge regarding drug-associated and drug-induced thrombosis are essential and have the potential to lead to decreased future incidence of thrombosis. The mechanisms at the basis of the thrombophilic activity of these drugs are variable and sometimes still ill recognized. Increased levels of clotting factors, reduction in coagulation natural inhibitors, decreased fibrinolysis, activated clotting factors, increased blood viscosity, endothelial damage, and increased platelet number and activation are the most frequent causes. Arterial steal or coronary arteries no flow has also been implicated. In some cases due to the intake of several drugs, more than one mechanism is present in a given patient. The purpose of the present review is to analyze all the drugs demonstrated to be potentially thrombotic. It is hoped that a prudent use or nonuse of these drugs might result in a reduction of thrombosis-associated diseases.

PMID: 27301402 [PubMed - indexed for MEDLINE]

Is the higher incidence of clozapine induced myocarditis in Australia due to awareness and monitoring?

Schizophr Res. 2018 Jun 13;:

Authors: Dawson JL, Clark SR, Sluggett JK, Procter NG, Simon Bell J

PMID: 29907491 [PubMed - as supplied by publisher]

Steroid-induced hyperglycemia: An underdiagnosed problem or clinical inertia? A narrative review.

Diabetes Res Clin Pract. 2018 May;139:203-220

Authors: Bonaventura A, Montecucco F

Abstract
Corticosteroids are widely diffused drugs. An important side effect is the impairment of glycemic control both in patients with known diabetes and in normoglycemic ones potentially leading to steroid-induced diabetes mellitus (SIDM). In this review based on papers released on PubMed, MEDLINE, and EMBASE from January 2015 to October 2017, we summarized and discussed main updates about the definition, the diagnosis, and the pathophysiology of steroid-induced hyperglycemia (SIH), with a look to new therapies. Main alterations responsible for the diabetogenic effect of corticosteroids are a negative impact on insulin sensitivity along with a derangement on insulin secretion, explaining the typical post-prandial hyperglycemia linked to the promotion of gluconeogenesis. An early and precise diagnosis of SIH and/or SIDM is necessary, but current criteria do not seem sensible enough. As an afterthought, the treatment should be reasoned and tailored according to proposed glycemic thresholds and patient comorbidities, choosing between antidiabetic oral drugs and insulin, the latter being preferable among hospitalized patients. SIDM and SIH are frequent problems, but often underdiagnosed due to old diagnostic criteria. Dedicated guidelines universally shared are mandatory in order to harmonize the treatment of these conditions, thus overtaking single therapeutic strategies mostly arising from literature.

PMID: 29530386 [PubMed - indexed for MEDLINE]

Pharmacokinetic drug-drug interactions in the intensive care unit - single-centre experience and literature review.

Anaesthesiol Intensive Ther. 2017;49(4):259-267

Authors: Łój P, Olender A, Ślęzak W, Krzych ŁJ

Abstract
BACKGROUND: Drug-drug interactions constitute a serious health hazard in everyday clinical practice in critically ill patients. Drug-drug interactions may be pharmacokinetic or pharmacodynamic in their nature. We aimed to investigate the quantity and quality of possible drug-drug interactions, and their possible side effects in intensive care unit patients in a 12-month period.
METHODS: This retrospective study covered data on pharmacological treatment of 43 consecutive patients (11 females, 32 males) aged 62 ± 15 years, hospitalized between January 2015 and February 2016. Pharmacokinetic DDIs were identified and graded. Only severe and clinically important drug-drug interactions were subjected for further analysis.
RESULTS: Median baseline SAPS III was 53 (IQR 38-67) points. Median intensive care unit stay was 12 (6-25) days. Subjects were treated with a median number of 22 (12-27) drugs. We identified 27 (16-41) possible drug-drug interactions per patient, including 3 (1-7) drug-drug interactions of a severe grade. The total number of severe and clinically important drug-drug interactions was 253 of which 227 were analyzed in detail. No possible side-effects of drug-drug interactions were identified.
CONCLUSIONS: DDIs as well as their side-effects are challenging regarding their precise evaluation, especially due to the need for multidrug treatment in critically ill patients. Concentration-controlled therapy should be recommended, especially for treatment with vancomycin, digoxin and valproate. Pantoprazole should be a proton pump-inhibitor of choice. Drug dose modification is necessary in combined treatment with fluconazole and amiodarone or rifampicin. From a clinical point of view, the most important impact of drug-drug interactions is on antibiotic treatment effectiveness, especially with meropenem when valproate is also prescribed.

PMID: 29027654 [PubMed - indexed for MEDLINE]