Agreement between renal prescribing references and determination of prescribing appropriateness in hospitalized patients with chronic kidney disease.

QJM. 2017 Oct 01;110(10):623-628

Authors: O'Shaughnessy M, Allen N, O'Regan J, Payne-Danson E, Mentre L, Davin D, Lavin P, Grimes T

Abstract
Background: Chronic kidney disease (CKD) is a risk factor for adverse drug events. The clinical significance of discordance between renal prescribing references is unknown.
Aim: We determined the prevalence of potentially inappropriate prescribing (PIP) in CKD, measured agreement between two prescribing references, and assessed potential for harm consequent to PIP.
Design: Single-centre observational study.
Methods: A random sample of hospitalized patients with CKD were grouped according to baseline CKD stage (3, 4, or 5). Prescriptions requiring caution in CKD were referenced against the Renal Drug Handbook (RDH) and British National Formulary (BNF) to identify PIP (non-compliance with recommendations). Inter-reference agreement was measured using percentage agreement and Kappa coefficient. Potential for harm consequent to PIP was assessed by physicians and pharmacists using a validated scale. One-year mortality was compared between patients with or without PIP during admission.
Results: Among 119 patients (median age 73 years, 50% male), 136 cases of PIP were identified in 78 (65.5%) patients. PIP prevalence, per patient, was 64.7% using the BNF and 28.6% using the RDH (fair agreement, Kappa 0.33, P <  0.001). The majority (63.2%) of PIP cases detected exclusively by the BNF carried minimal or no potential for harm. PIP was not significantly associated with one-year mortality (34.7% vs. 21.1%, P = 0.14).
Conclusions: PIP was common in hospitalized patients with CKD. Substantial discordance between renal prescribing references was apparent. The development of universally-adopted, evidence-based, prescribing guidelines for CKD might optimize medications safety in this vulnerable group.

PMID: 28431157 [PubMed - indexed for MEDLINE]

A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP.

Forensic Sci Int. 2017 Jun;275:76-82

Authors: Johansson A, Lindstedt D, Roman M, Thelander G, Nielsen EI, Lennborn U, Sandler H, Rubertsson S, Ahlner J, Kronstrand R, Kugelberg FC

Abstract
INTRODUCTION: 3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016.
CASE DESCRIPTIONS: The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse.
METHODS: 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry.
RESULTS: In the clinical case, the concentration of 3-MeO-PCP was 0.14μg/g at admission, 0.08μg/g 2.5h after admission, 0.06μg/g 5h after admission and 0.04μg/g 17h after admission. The half-life of 3-MeO-PCP was estimated to 11h. In the autopsy cases, femoral blood concentrations ranged from 0.05μg/g to 0.38μg/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well.
CONCLUSION: Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment.

PMID: 28324770 [PubMed - indexed for MEDLINE]

Autoimmune Hepatitis in the Elderly: Diagnosis and Pharmacologic Management.

Drugs Aging. 2018 Jul 04;:

Authors: Rizvi S, Gawrieh S

Abstract
Autoimmune hepatitis (AIH) may present as acute or chronic hepatitis in the elderly. Advanced hepatic fibrosis and cirrhosis are common on first presentation in this population. In this review, we discuss the presentation, approach to diagnosis and management of AIH in the elderly. As polypharmacy is common in the elderly, careful medication use history is essential for detecting drug-induced AIH-like hepatitis. Steroid-sparing or minimizing therapeutic regimens are preferred to treat AIH in the elderly. For the purpose of induction, budesonide or lower dose prednisone in combination with azathioprine (AZA) regimens are preferred over high-dose prednisone monotherapy due to the higher risk of side effects of the later in the elderly. The goal of maintenance therapy should be to achieve full biochemical and histologic remission. Bone density monitoring and interventions to prevent steroid-related bone disease should be implemented throughout the course of the disease. Liver transplantation should be considered in the elderly patient with liver failure or early hepatocellular carcinoma if there are no significant comorbidities or compromise in functional status.

PMID: 29971609 [PubMed - as supplied by publisher]

Safety and immune response after two-dose meningococcal C conjugate immunization in HIV-infected children and adolescents in Rio de Janeiro, Brazil.

Vaccine. 2017 12 15;35(50):7042-7048

Authors: Frota ACC, Ferreira B, Harrison LH, Pereira GS, Pereira-Manfro W, Machado ES, de Oliveira RH, Abreu TF, Milagres LG, Hofer CB

Abstract
We aimed to evaluate immunogenicity and adverse events (AEs) after a booster dose of Meningococcal C conjugated (MCC) vaccine in HIV-infected children and adolescents, who had a previous low seroconversion rate after priming with MCC, at a reference HIV-care center in Rio de Janeiro.
METHODS: 2-18 years old HIV-infected subjects with CD4+ T-lymphocyte cell (CD4) ≥15%, without active infection or antibiotic use, were enrolled to receive 2 doses of conjugated meningococcal C oligosaccharide-CRM197 12-18 months apart. All patients were evaluated before and 1-2 months after immunization for seroprotection [defined as human serum bactericidal activity (hSBA) titer ≥1:4]. AEs were assessed at 20 min, 3 and 7 days after each dose. Factors independently associated with seroprotection were studied.
RESULTS: 156 subjects were enrolled and 137 received a booster MCC dose. 55% were female, and median age was 12 years. Eight-nine percent were receiving combined antiretroviral therapy (cART) at the booster visit (median duration of 7.7 years), 59.9% had undetectable viral load (VL) at baseline, and 56.2% at the booster visit. Seroprotection was achieved in 78.8% (108/137) subjects, with a significantly higher GMT than after the priming dose (p < 0.01). Mild AEs were experienced after a second MCC dose (38%). In logistic regression, undetectable viral load at entry [odds ratio (OR) = 7.1, 95% confidence interval (95%CI): 2.14-23.37], and probably higher CD4 percent at the booster immunization visit (OR): 1.1, 95%CI: 1.01-1.17 were associated with seroprotection after a booster dose of MCC.
CONCLUSION: A booster dose of MCC was safe and induced high seroprotection rate even 12-18 months after priming. MCC should be administered after maximum virologic suppression has been achieved. These results support the recommendation of 2-dose of MCC for primary immunization in HIV-infected children and adolescents with restored immune function.

PMID: 29100708 [PubMed - indexed for MEDLINE]

A multi-site feasibility study to assess fever and wheezing in children after influenza vaccines using text messaging.

Vaccine. 2017 12 15;35(50):6941-6948

Authors: Stockwell MS, Marchant CD, Wodi AP, Barnett ED, Broder KR, Jakob K, Lewis P, Kattan M, Rezendes AM, Barrett A, Sharma D, Fernandez N, LaRussa P

Abstract
BACKGROUND: Using text messaging for vaccine safety monitoring, particularly for non-medically attended events, would be valuable for pandemic influenza and emergency vaccination program preparedness. We assessed the feasibility and acceptability of text messaging to evaluate fever and wheezing post-influenza vaccination in a prospective, observational, multi-site pediatric study.
METHODS: Children aged 2-11 years old, with an emphasis on children with asthma, were recruited during the 2014-2015 influenza season from three community-based clinics in New York City, and during the 2014-2015 and 2015-2016 seasons from a private practice in Fall River, Massachusetts. Parents of enrolled children receiving quadrivalent live attenuated (LAIV4) or inactivated influenza vaccine (IIV4) replied to text messages assessing respiratory symptoms (day 3 and 7, then weekly through day 42), and temperature on the night of vaccination and the next seven nights (day 0-7). Missing data were collected via diary (day 0-7 only) and phone. Phone confirmation was obtained for both presence and absence of respiratory symptoms. Reporting rates, fever (T≥100.4 °F) frequency, proportion of wheezing and/or chest tightness reports captured via text message versus all sources (text, phone, diary, electronic health record) and parental satisfaction were assessed.
RESULTS: Across both seasons, 266 children were analyzed; 49.2% with asthma. Parental text message response rates were high (>70%) across sites. Overall, fever frequency was low (day 0-2: 4.1% [95% confidence interval (CI) 2.3-7.4%]; d3-7: 6.7% [95% CI 4.1-10.8%]). A third (39.2%) of parents reported a respiratory problem in their child, primarily cough. Most (88.2%) of the 52 wheezing and/or chest tightness reports were by text message. Most (88.1%) participants preferred text messaging over paper reporting.
CONCLUSIONS: Text messaging can provide information about pediatric post-vaccination fever and wheezing and was viewed positively by parents. It could be a helpful tool for rapid vaccine safety monitoring during a pandemic or other emergency vaccination program.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02295007.

PMID: 29089191 [PubMed - indexed for MEDLINE]

Immediate hypersensitivity to penicillins. Identification of a new antigenic determinant.

J Pharm Biomed Anal. 2018 Jan 30;148:17-23

Authors: Matas S, Broto M, Corominas M, Lleonart R, Babington R, Marco MP, Galve R

Abstract
The study of adverse drug reactions (ADRs) constitutes a challenge in the area of Medicine. Drugs generate a large number of the total registered hypersensitivity reactions, where penicillins are responsible for more than half of them. In vitro tests in the market are not efficient enough since they lack in sensitivity and specificity. This is the reason why in vivo tests are carried out, with the subsequent danger to the patient's life. It is essential to discover new β-lactam antigenic determinants to develop more effective detection systems and thus, obtain better explanations of the allergic mechanisms related to these drugs. We propose a strategy based on the use of "peptide probes", small labeled and chemical active peptides which have been structurally modified for reacting with the β-lactam moiety at different conditions. The probes also contain a biotin group for application in an immunoassay format. Three different amoxicillin adducts have been obtained, purified and characterized by HPLC-MS and NMR techniques. These results have helped us to elucidate and propose a new antigenic determinant for β-lactams, named the "penamidyl" epitope. All the adducts have been validated and evaluated with sera from different penicillin allergic patients by means of a Magneto-ELISA, immunochemical technique that has allowed us to detect specific IgEs in a very high percentage of the serum samples. An immunoassay has been developed, validated and applied as a diagnostic tool for the detection of specific IgEs in the sera of penicillin allergic patients using a new antigenic determinant.

PMID: 28987997 [PubMed - indexed for MEDLINE]

Prescribing cascade. A proposed new way to evaluate it.

Medicina (B Aires). 2017;77(1):13-16

Authors: Ponte ML, Wachs L, Wachs A, Serra HA

Abstract
Prescribing cascade is defined as the situation in which a first drug administered to a patient causes adverse event signs and symptoms, that are misinterpreted as a new condition, resulting in a new medication being prescribed. The cascade may have multiple steps and differ in complexity and severity. Despite being well identified, prescribing cascade is an increasingly common problem in medical practice. It constitutes a warning about irrational use of medicines that puts health at risk and increases treatment costs if it is not taken into account. In this article, representative cases taken from Hospital General de Agudos Dr. Cosme Argerich pharmacovigilance database were selected to assess a proper score and an algorithm that define the probable prescribing cascade.

PMID: 28140305 [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 2018/07/03

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.

The Hemodynamic Effects of Intracavernosal Phenylephrine for the Treatment of Ischemic Priapism.

J Sex Med. 2018 Jul;15(7):990-996

Authors: Sidhu AS, Wayne GF, Kim BJ, Anderson AGS, Cordon BH, Caso JR, Polackwich AS

Abstract
AIM: We sought to evaluate whether the administration of phenylephrine (PE) at concentrations higher than those described in guidelines resulted in any significant changes in vital signs or impacted outcomes.
METHODS: After receiving institutional review board approval, we retrospectively reviewed the charts of patients presenting to our emergency department between May 1, 2014, and August 15, 2016, using International Classification of Diseases, Ninth Edition and Internation Classification of Disease, Tenth Edition diagnosis codes for priapism. Treatment was reviewed, including corporal aspiration/irrigation, injection of PE, and shunt procedures. Vital signs were compared before and after treatment with PE. Baseline variables were explored with categorical data analysis (chi-squared tests, t-tests, and Mann-Whitney nonparametric tests). Where feasible, linear regression was used to evaluate outcomes.
MAIN OUTCOME MEASURE: Detumescence and changes in blood pressure and heart rate.
RESULTS: We identified 74 different patient encounters of acute priapism. The median age was 36.5 years (interquartile range [IQR] = 27-47), and the median time to presentation was 5.4 hours (IQR = 4.0-9.6). 62 percent of cases were due to drug-induced priapism. In 58 (74%) encounters, patients received PE. The median dose of PE given was 1000 μg (IQR 500-2,000). Univariate regression found no association between PE dose and change in patient heart rate or blood pressure. A statistically significant decrease in heart rate (HR) (-4.2 BPM), systolic blood pressure (BP) (-1.8 mm Hg), and diastolic BP (-5.4 mm Hg) was noted. Fifty-three of 58 (91%) patients receiving PE experienced detumescence at the bedside, 2 required shunting in operating room, and 3 refused treatment and left against medical advice. No adverse events occurred.
CONCLUSION: We frequently treat patients with high doses of PE and seldom notice adverse effects, typically resulting in resolution of priapism without any additional procedures. Careful administration of high doses of intracavernosal PE in patients presenting with priapism does not appear to significantly affect heart rate or blood pressure and may help prevent further ischemic damage and achieve detumescence effectively and efficiently. Sidhu AS, Wayne GF, Kim BJ, et al. The hemodynamic effects of intracavernosal phenylephrine for the treatment of ischemic priapism. J Sex Med 2018;15:990-996.

PMID: 29960632 [PubMed - in process]

Glycoprotein IIb/IIIa receptor imaging with 18F-GP1 positron emission tomography for acute venous thromboembolism: an open-label, non-randomized, first-in-human phase 1 study.

J Nucl Med. 2018 Jun 29;:

Authors: Kim C, Lee JS, Han Y, Chae SY, Jin S, Sung C, Son HJ, Oh SJ, Lee SJ, Oh JS, Cho YP, Kwon TW, Lee DH, Jang S, Kim B, Koglin N, Berndt M, Stephens AW, Moon DH

Abstract
18F-GP1 is a derivative of elarofiban with a high affinity to activated platelet glycoprotein IIb/IIIa (GPIIb/IIIa) and favorable in vivo characteristics for thrombus imaging in preclinical models. We aimed to explore the detection rate of thromboembolic foci with 18F-GP1 positron emission tomography/computed tomography (PET/CT) in patients with acute venous thromboembolism (VTE), and to evaluate the safety, biodistribution, pharmacokinetics, and metabolism of 18F-GP1. Methods: We studied patients who had signs or symptoms of acute deep vein thrombosis (DVT) of the leg or acute pulmonary embolism (PE) within 14 days prior to 18F-GP1 PET/CT, and had thromboembolic foci confirmed by conventional imaging (n = 10 for DVT and n = 10 for PE). Dynamic whole-body PET/CT images were acquired for up to 140 minutes after injection of 250 MBq of 18F-GP1. Results:18F-GP1 PET/CT was well tolerated without any drug-related adverse events, and showed high initial uptake in spleen, kidney, and blood pool, followed by rapid clearance. The overall image quality was excellent and allowed interpretation in all patients. 18F-GP1 PET/CT identified thromboembolic foci in all 20 patients with either DVT or PE. Vessel-level analysis revealed that 18F-GP1 PET/CT detected 89% (68/76) of vessels with DVT, and 60% (146/245) for PE. Importantly, 18F-GP1 PET/CT showed increased uptake in 32 vessels that were not detected by conventional imaging, of which 25 were located in distal veins of the lower extremity in 12 patients. A positive correlation was found between 18F-GP1 uptake and P-selectin-positive circulating platelets (r = 0.656, P = 0.002). Conclusion:18F-GP1 is a promising PET tracer for imaging acute VTE in patients. 18F-GP1 PET/CT may identify thrombi in distal veins of the leg, where conventional imaging has limitations.

PMID: 29959214 [PubMed - as supplied by publisher]

A meta-learning framework using representation learning to predict drug-drug interaction.

J Biomed Inform. 2018 Jun 26;:

Authors: Deepika SS, Geetha TV

Abstract
MOTIVATION: Predicting Drug-Drug Interaction (DDI) has become a crucial step in the drug discovery and development process, owing to the rise in the number of drugs co-administered with other drugs. Consequently, the usage of computational methods for DDI prediction can greatly help in reducing the costs of in vitro experiments done during the drug development process. With lots of emergent data sources that describe the properties and relationships between drugs and drug-related entities (gene, protein, disease, and side effects), an integrated approach that uses multiple data sources would be most effective.
METHOD: We propose a semi-supervised learning framework which utilizes representation learning, positive- unlabeled (PU) learning and meta-learning efficiently to predict the drug interactions. Information from multiple data sources is used to create feature networks, which is used to learn the meta-knowledge about the DDIs. Given that DDIs have only positive labeled data, a PU learning-based classifier is used to generate meta-knowledge from feature networks. Finally, a meta-classifier that combines the predicted probability of interaction from the meta-knowledge learnt is designed.
RESULTS: Node2vec, a network representation learning method and bagging SVM, a PU learning algorithm, are used in this work. Both representation learning and PU learning algorithms improve the performance of the system by 22% and 12.7% respectively. The meta-classifier performs better and predicts more reliable DDIs than the base classifiers.

PMID: 29959033 [PubMed - as supplied by publisher]

[Bilateral uveitis associated with nivolumab therapy].

J Fr Ophtalmol. 2018 Jun 26;:

Authors: Rémond AL, Barreau E, Le Hoang P, Bodaghi B

Abstract
Immune-related adverse events (IRAEs) are rare but serious adverse events that may be associated with inhibitors of few immune control points. The purpose here is to report the case of an inflammatory ocular disease, potentially linked to the immunity and use of nivolumab, a new immunological agent used for the treatment of a solid tumor. In spite of the involvement of this treatment in the onset of inflammation, we must always seek another cause. It is possible to continue this treatment by considering the benefit/risk balance for each patient. Close collaboration between oncologists and ophthalmologists is necessary in the diagnosis and rapid management of these IRAE ocular related to these new emerging therapies.

PMID: 29958705 [PubMed - as supplied by publisher]

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 2018/06/30

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.

Efficacy and safety of the combination fluticasone propionate plus salmeterol in asthmatic preschoolers: An observational study.

J Asthma. 2018 Jun 29;:1-8

Authors: Hatziagorou E, Kouroukli E, Galogavrou M, Papanikolaou D, Terzi DD, Anagnostopoulou P, Kirvassilis F, Panagiotakos DB, Tsanakas J

Abstract
BACKGROUND: Inhaled Corticosteroids (ICS) are the cornerstone of asthma management in pediatric patients. However, in some cases, asthma is not adequately controlled on ICS alone. Long-acting beta2-agonists (LABA) are one of the available additional therapies but their use has rarely been studied among children younger than 5 years.
OBJECTIVE: The aim of this observational study was to evaluate the efficacy and safety of the combination of fluticasone propionate and salmeterol (FP/SA) in asthmatic children younger than 5 years of age.
METHODS: A retrospective study of 796 children under the age of 5 years (2.87 ± 1.22 years, 64.2% males), who were treated with FP/SA was conducted. Hospitalization rates, frequency of wheezing, exercise induced asthma, nocturnal wheeze and drug-related side-effects were recorded through children's medical records.
RESULTS: The children had previously received short-acting β2-agonists (73%), ICS (17%), montelukast (1%), and ICS with montelukast (2%). Mean duration of therapy with FP/SA was 12.45 ± 9.14 months. After adjusting for age, gender, and duration of treatment, a 89% reduction was recorded in annual hospitalization rates (from 27.13% before treatment to 3.01% after FP/SA therapy, p < 0.001), a 71% reduction in incidence of exercise-induced asthma (36.8% vs. after 10.6%, p < 0.001), a 81% reduction in nocturnal asthma (33.7% vs. after: 6.4%, p < 0.001), as well as in frequency of wheezing (p < 0.01),. No previous treatment carry-on effect was observed. No major drug-related side-effects occurred in the study group.
CONCLUSIONS: Combination therapy (FP/SA) is well-tolerated and highly effective in asthmatic children under the age of 5 years.

PMID: 29958011 [PubMed - as supplied by publisher]

Efficacy and Safety of Estradiol Valerate/Dienogest for the Management of Heavy Menstrual Bleeding: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase III Clinical Trial.

J Womens Health (Larchmt). 2018 Jun 29;:

Authors: Yu Q, Zhou Y, Suturina L, Jaisamrarn U, Lu D, Parke S

Abstract
BACKGROUND: To investigate the efficacy and safety of estradiol valerate (EV)/dienogest (DNG) for the management of heavy menstrual bleeding (HMB) in Asian and non-Asian women desiring contraception.
MATERIALS AND METHODS: In this multicenter, double-blind, phase III study, women were randomized 2:1 to receive EV/DNG or placebo tablets daily for seven 28-day cycles. The primary endpoint was the absolute change in menstrual blood loss (MBL) volume between the run-in and efficacy phases (90 days each). Secondary endpoints included the proportion of women with successful treatment (i.e., no episodes of MBL ≥80 mL and a decrease of <50% in MBL), percent change in MBL from the run-in phase, and change in hemoglobin and serum ferritin levels. Adverse events (AEs) were monitored throughout the study.
RESULTS: Of the 341 women (mean age 34.7 ± 7.7 years; 309 Asians, 32 non-Asians) randomized, 270 completed the study. Mean reduction in MBL volume from run-in phase was significantly greater with EV/DNG than placebo (366.75 mL vs. 149.14 mL; p < 0.0001), with ∼52% and 12% of women, respectively, experiencing successful treatment. Percent decrease in MBL volume from the run-in phase was significantly greater with EV/DNG than placebo (63.5% vs. 24.8%; p < 0.0001). Hemoglobin and serum ferritin levels were increased with EV/DNG compared with placebo. Study drug-related AEs were reported in 16.3% and 8.2% of women with EV/DNG and placebo, respectively, none of which were of severe intensity.
CONCLUSIONS: EV/DNG may be a safe and effective option in the treatment of HMB in Asian and non-Asian women who desire contraception.

PMID: 29957101 [PubMed - as supplied by publisher]

A randomized, open-label, crossover study evaluating bioequivalence of two N-acetylcysteine 2% oral solution formulations in healthy subjects
.

Int J Clin Pharmacol Ther. 2018 Jun 29;:

Authors: Donath F, Armogida M, Shneyer L

Abstract
OBJECTIVE: N-acetylcysteine is a mucolytic agent used to treat bronchopulmonary diseases associated with airway mucus hypersecretion. The bioequivalence of a new oral N-acetylcysteine 2% formulation was evaluated relative to an appropriate reference product.
MATERIALS AND METHODS: This open-label, randomized, crossover study assessed the bioequivalence of a new N-acetylcysteine 2% oral solution compared to an approved reference N-acetylcysteine 2% oral solution in healthy subjects in terms of pharmacokinetics, including area under the plasma concentration vs. time curve of N-acetylcysteine plasma concentrations from time 0 to the last measurable sampling time point and the maximum postdose concentration. Bioequivalence was concluded if the 90% confidence intervals for the ratio of the geometric means of the two pharmacokinetic parameters with baseline correction were entirely within the range of 80 - 125%.
RESULTS: 46 participants were randomized. The ratios of the geometric means for the test vs. reference treatment, with baseline correction, were 1.0961 (90% confidence interval: 1.0228, 1.1746) for area under the plasma concentration curve of test N-acetylcysteine plasma concentrations and 1.0938 (90% confidence interval: 1.0142, 1.1796) for maximum postdose concentration; both were within the predefined range to demonstrate bioequivalence. Most treatment-emergent adverse events were mild or moderate and not considered study drug related.
CONCLUSION: The new N-acetylcysteine 2% oral solution was found to be bioequivalent to the marketed reference formulation. Treatments were generally safe and well tolerated.
.

PMID: 29956648 [PubMed - as supplied by publisher]

Reversible pancytopenia caused by severe copper deficiency in a patient with Wilson disease.

Med J Aust. 2018 Jun 02;209(1):1112

Authors: Mohamed M, Johnston A, Maclaine Cross A, Sharma A

PMID: 29954304 [PubMed - in process]

Adverse Event Profile of Pyrimethamine-Based Therapy in Toxoplasmosis: A Systematic Review.

Drugs R D. 2017 Dec;17(4):523-544

Authors: Ben-Harari RR, Goodwin E, Casoy J

Abstract
INTRODUCTION: Approximately a third of the population worldwide is chronically infected with Toxoplasma gondii. Pyrimethamine-based regimens are recommended for the treatment of toxoplasmosis.
OBJECTIVE: The aim was to evaluate the safety profile of pyrimethamine-based treatment for the three main Toxoplasma manifestations: toxoplasmic encephalitis (TE), ocular toxoplasmosis, and congenital toxoplasmosis.
METHODS: PubMed, Cochrane Library, and Google Scholar databases were searched through August 1, 2016. Randomized, observational, prospective/retrospective, and cohort studies were eligible. Thirty-one studies were included with a total of 2975 patients. Of these, 13 were in congenital toxoplasmosis (n = 929), 11 in ocular toxoplasmosis (n = 1284), and seven in TE (n = 687). Across manifestations, adverse event (AE)-related treatment discontinuation and/or change in therapy involved ≤37% of patients and occurred in >55% of studies: 100% for ocular toxoplasmosis, 57.1% for TE, and 61.5% for congenital toxoplasmosis. The most commonly observed AEs were bone marrow suppression, dermatologic, and gastrointestinal (GI). The prevalence of bone marrow suppression-related AEs was ≤50% in congenital toxoplasmosis, ≤42.7% in TE, and ≤9.0% in ocular toxoplasmosis. The frequency of GI and dermatologic AEs were ≤100 and ≤11.1%, respectively, for ocular toxoplasmosis, ≤10.7 and ≤17.9% for TE, and ≤10.8 and ≤2.1% for congenital toxoplasmosis. Steven-Johnson syndrome was reported in two patients with ocular toxoplasmosis and one with TE.
CONCLUSION: The AE profile associated with pyrimethamine-based treatments differed by each manifestation of toxoplasmosis and within a given manifestation. Hematologic AEs occurred across all manifestations indicating the importance of monitoring the blood of patients administered pyrimethamine-based regimens.

PMID: 28879584 [PubMed - indexed for MEDLINE]

Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research.

Drugs R D. 2017 Dec;17(4):493-507

Authors: Brandt J, Leong C

Abstract
Various adverse events resulting from, or associated with, benzodiazepine and/or Z-drug use have been extensively reported on and discussed in great detail within the biomedical literature. It is widely accepted that motor vehicle accidents and falls leading to fractures in older adults are major adverse events that have been shown to occur more frequently in users of sedative-hypnotic medication, especially of the benzodiazepine and related Z-drug variety. However, the last few years have seen increasing reports in the literature raising the issue of benzodiazepine and Z-drug exposure in the development of other serious medical issues including dementia, infections, respiratory disease exacerbation, pancreatitis, and cancer. This article provides an overview and interpretation on the current state of evidence regarding each of these associations and proposes what gaps in the evidence for drug-exposure-harm associations need to be addressed in the future for the purpose of evaluating causality of harm as it relates to these drugs.

PMID: 28865038 [PubMed - indexed for MEDLINE]

[Systematic review of Kudiezi injection drug safety].

Zhongguo Zhong Yao Za Zhi. 2017 Jun;42(12):2380-2390

Authors: Gao SS, Cui RZ, Xie YM, Liao X, Gao XY, Wang JD

Abstract
To systematically evaluate the safety of Kudiezi injection. Databases such as Cochrane library, Medline, EMbase, Web of Science, Clinical Trials, CBM, CNKI, VIP, Wanfang and Chinese Clinical Trial Register were searched to collect the literature on all the study types of Kudiezi injection. Two researchers screened literature, assessed quality and extracted data according to inclusion and exclusion criteria. All studies were assessed by using internationally recognized methodological quality assessment tools or reporting quality evaluation criteria; Meta-analysis of adverse drug reaction/adverse events (ADR/AE) of Kudiezi injection was performed by using Stata 12.0 software. There were 411 clinical studies included, out of which 315 studies were analyzed finally. 18 072 patients in total used kudiezi injection, and there were 330 cases with ADRs and 13 cases with AEs. The most common ADR related system was the central and peripheral nervous system, with a weighted incidence of 2.9% [95%CI(0.022, 0.036)]. From the current evidence, the overall safety of Kudiezi injection was acceptable. Although data could be collected from all kinds of published reports, there are lack of mechanism experiments or observational studies with large samples of Kudiezi injection. Therefore, it is necessary to carry out further research on the safety of Kudiezi injection. Meanwhile, off label use of Kudiezi injection is common, so it is urgent for relevant governmental departments to formulate drug use specifications and provide better guidance for clinical drug use.

PMID: 28822197 [PubMed - indexed for MEDLINE]