Development of a Physiologically Based Pharmacokinetic Model of Ethionamide in the Pediatric Population by Integrating Flavin-Containing Monooxygenase 3 Maturational Changes Over Time.

J Clin Pharmacol. 2018 Jun 07;:

Authors: Nguyen PTT, Parvez MM, Kim MJ, Ho Lee J, Ahn S, Ghim JL, Shin JG

Abstract
Currently, ethionamide is the most frequently prescribed second-line antituberculosis drug in children. After extensive metabolism by flavin-containing monooxygenase (FMO) isoform 3 in the liver, the drug may exert cytotoxic effects. The comparison of children in different age groups revealed a significant age-related increase in ethionamide elimination in vivo. However, to date, the exact mechanism underlying this dynamic increase in ethionamide elimination has not been elucidated. We hypothesized that the age-dependent changes in ethionamide elimination were predominantly a result of the progressive increases in the expression and metabolic capacity of FMO3 during childhood. To test this hypothesis, a full physiologically based pharmacokinetic (PBPK) model of ethionamide was established and validated in adults through incorporation of comprehensive metabolism and transporter profiles, then expanded to the pediatric population through integration of FMO3 maturational changes over time. Thus, a good prediction PBPK model was validated successfully both in adults and children and applied to demonstrate the critical contribution of FMO3 in the mechanistic elimination pathway of ethionamide. In addition, a significant correlation between clearance and age was observed in children by accounting for ethionamide maturation, which could offer a mechanistic understanding of the age-associated changes in ethionamide elimination. In conclusion, this study underlines the benefits of in vitro-in vivo extrapolation and a quantitative PBPK approach for the investigation of transporter-enzyme interplay in ethionamide disposition and the demonstration of FMO3 ontogeny in children.

PMID: 29878384 [PubMed - as supplied by publisher]

Aciclovir CSF concentration in children with viral encephalitis: is it adequate?

J Antimicrob Chemother. 2018 Jun 06;:

Authors: Sun SZ, Wang L, Wu YE, Ma GL, Yao BF, Dong L, Jacqz-Aigrain E, Shi ZR, Zhao W

PMID: 29878193 [PubMed - as supplied by publisher]

Pharmacogenomics: Precision Pharmacy in 503A Compounding.

Int J Pharm Compd. 2018 Mar-Apr;22(2):95-107

Authors: Drummond J, Bennet D, Allen LV

Abstract
The first recorded mention of a pharmacogenomic response may be that of Pythagoras in 510 BC, when he noted that hemolytic anemia developed in some but not all people who ingested fava beans. The application of such accounts to pharmacotherapy was inevitable, and customized medications have been compounded since antiquity to treat the needs of individual patients. Today, advances in pharmacogenomic testing yield results that enable more effective targeted therapies sooner in the course of treatment, prevent drug-related adverse effects, save cost, and ensure a better therapeutic outcome. The value of such testing is now more widely accepted, even in the public domain. It is our opinion that third-party payors will realize, to an increasing degree, that this new technology will save them money and will pay for it. Because independent compounding pharmacists have trusted relationships with patients and are convenient to visit, they are well placed to offer certain types of pharmacogenomic tests to patients and prescribers. In this article, topics that we address include the difference between pharmacogenomics and pharmacogenetics; the use of pharmacogenomic testing in 503A compounding; the benefits of such tests for patients, prescribers, and compounders; and suggestions for marketing pharmacogenomics testing. Information about a course that introduces pharmacogenomic science to compounders is provided, and suggestions for additional reading and other resources about pharmacogenomic testing are included for easy reference.

PMID: 29877857 [PubMed - in process]

Stargazer: a software tool for calling star alleles from next-generation sequencing data using CYP2D6 as a model.

Genet Med. 2018 Jun 06;:

Authors: Lee SB, Wheeler MM, Patterson K, McGee S, Dalton R, Woodahl EL, Gaedigk A, Thummel KE, Nickerson DA

Abstract
PURPOSE: Genotyping CYP2D6 is important for precision drug therapy because the enzyme it encodes metabolizes approximately 25% of drugs, and its activity varies considerably among individuals. Genotype analysis of CYP2D6 is challenging due to its highly polymorphic nature. Over 100 haplotypes (star alleles) have been defined for CYP2D6, some involving a gene conversion with its nearby nonfunctional but highly homologous paralog CYP2D7. We present Stargazer, a new bioinformatics tool that uses next-generation sequencing (NGS) data to call star alleles for CYP2D6 ( https://stargazer.gs.washington.edu/stargazerweb/ ). Stargazer is currently being extended for other pharmacogenes.
METHODS: Stargazer identifies star alleles from NGS data by detecting single nucleotide variants, insertion-deletion variants, and structural variants. Stargazer detects structural variation, including gene deletions, duplications, and conversions, by calculating paralog-specific copy numbers from read depths.
RESULTS: We applied Stargazer to the NGS data of 32 ethnically diverse HapMap trios that were genotyped by TaqMan assays, long-range polymerase chain reaction, quantitative multiplex polymerase chain reaction, high-resolution melting analysis, and/or Sanger sequencing. CYP2D6 genotyping by Stargazer was 99.0% concordant with the data obtained by these methods, and showed that 28.1% of the samples had structural variation including CYP2D6/CYP2D7 hybrids.
CONCLUSION: Accurate genotyping of pharmacogenes with NGS and subsequent allele calling with Stargazer will aid the implementation of precision drug therapy.

PMID: 29875422 [PubMed - as supplied by publisher]

Clinical reappraisal of the influence of drug-transporter polymorphisms in epilepsy.

Expert Opin Drug Metab Toxicol. 2018 May;14(5):505-512

Authors: Orlandi A, Paolino MC, Striano P, Parisi P

Abstract
INTRODUCTION: Although novel antiepileptic drugs (AEDs) have been recently released, the issue of drug resistance in epileptic patients remains unsolved and largely unpredictable. Areas covered: We aim to assess the clinical impact of genetic variations that may influence the efficacy of medical treatment in epilepsy patients. Indeed, many genes, including genes encoding drug transporters (ABCB1), drug targets (SCN1A), drug-metabolizing enzymes (CYP2C9, CYP2C19), and human leucocyte antigen (HLA) proteins, may regulate the mechanisms of drug resistance in epilepsy. This review specifically focuses on the ABC genes, which encode multidrug resistance-associated proteins (MRPs) and may reduce the blood-brain barrier penetration of anticonvulsant AEDs. Expert opinion: Drug resistance remains a crucial problem in epilepsy patients. Pharmacogenomic studies may improve our understanding of drug responses and drug resistance by exploring the impact of gene variants and predicting drug responses and tolerability.

PMID: 29804481 [PubMed - indexed for MEDLINE]

Culture-independent Analysis of Pediatric Broncho-alveolar Lavage (BAL) Specimens.

Ann Am Thorac Soc. 2018 Jun 07;:

Authors: Zachariah P, Ryan C, Nadimpalli S, Coscia G, Kolb M, Smith H, Foca M, Saiman L, Planet PJ

Abstract
BACKGROUND: The clinical utility of culture-independent testing of pediatric bronchoalveolar lavage (BAL) specimens is unknown. Additionally, the variability of the pediatric pulmonary microbiome with patient characteristics is not well understood.
METHODS: Study subjects were ≤22 years old and underwent BAL from May 2013 - July 2015 as part of clinical care. DNA extracted from BAL specimens was used for 16S rRNA gene-based (16S-based) microbiome analysis, and results compared to routine cultures from the same samples. Indices of microbial diversity and relative taxon abundances were compared based on subject characteristics.
RESULTS: From 81 participants (51% male, median age 9 years), 89 samples were collected and the 16S rRNA genes of 77 (86.5%) samples were successfully analyzed. Subjects included 23 cystic fibrosis (CF), 19 immunocompromised (IC), and 28 non-immunocompromised (nIC) patients. Of 68 organisms identified in culture, 16S-based analyses were concordant with culture results in 66 (97.1%), and also identified potentially clinically significant taxa missed by cultures (e.g. Staphylococcus, Legionella, Pseudomonas). Significant differences in abundance were noted mostly for non-cultured taxa with diagnosis and antibiotic use (Veillonella, Corynebacterium, Haemophilus). The microbiota of CF samples was less diverse and a "core" group of fifteen taxa shared across samples was identified.
CONCLUSION: 16S-based culture independent analysis was concordant with routine cultures and showed potential to detect non-cultured pathogens. While 16S- based testing identified relative changes in organism abundance associated with clinical characteristics, distinct microbiome profiles associated with disease states were not identified.

PMID: 29877714 [PubMed - as supplied by publisher]

Cellulitis caused by the Burkholderia cepacia complex associated with contaminated chlorhexidine 2% scrub in five domestic cats.

J Vet Diagn Invest. 2018 Jun 01;:1040638718782333

Authors: Wong JK, Chambers LC, Elsmo EJ, Jenkins TL, Howerth EW, Sánchez S, Sakamoto K

Abstract
Isolates of the Burkholderia cepacia complex (BCC) are known as plant and human pathogens. We describe herein BCC infections as the cause of subcutaneous abscesses and purulent cellulitis in 5 cats. All cats were presented with an open wound, and 4 received standard wound care and empiric antibiotic therapy. Despite treatment, clinical signs worsened in 4 cats. Isolates of the BCC were obtained from all 5 cases. Two cats were submitted for postmortem examination. Subcutaneous abscesses with draining fistulas were observed. Histopathology revealed severe, pyogranulomatous cellulitis with intralesional gram-negative bacilli. Based on susceptibility results, the other 3 cats were administered effective antibiotics and recovered without complications. The BCC was cultured from the 2% chlorhexidine surgical scrub solution used in the clinic, suggesting the source of infection for 4 of 5 cats. Given the ability to grow in antiseptic solutions, the extra steps required to culture from antiseptics, and innate multidrug resistance, the BCC poses a challenge to both detect and treat. Although the BCC causes disease almost exclusively in humans with cystic fibrosis or immunodeficiency, the bacteria should also be a differential for nosocomial infections in veterinary patients.

PMID: 29877147 [PubMed - as supplied by publisher]

Subacute TGFβ Expression Drives Inflammation, Goblet Cell Hyperplasia, and Pulmonary Function Abnormalities in Mice with Effects Dependent on CFTR Function.

Am J Physiol Lung Cell Mol Physiol. 2018 Jun 07;:

Authors: Kramer EL, Hardie WD, Madala SK, Davidson CR, Clancy JP

Abstract
BACKGROUND: Cystic fibrosis (CF) produces variable lung disease phenotypes that are in part independent of CFTR genotype. Transforming growth factor beta (TGFβ) is the best described genetic modifier of the CF phenotype, but its mechanism of action is unknown. We hypothesized that TGFβ is sufficient to drive pathognomonic features of CF lung disease in vivo and that CFTR deficiency enhances susceptibility to pathologic TGFβ effects.
METHODS: A CF mouse model and littermate controls were exposed intratracheally to an adenoviral vector containing the TGFβ1 cDNA (Ad-TGFβ), empty vector, or PBS only. Studies were performed one week after treatment, including lung mechanics, collection of bronchoalveolar lavage fluid (BALF), and analysis of lung histology, RNA, and protein.
RESULTS: CF and non-CF mice showed similar weight loss, inflammation, goblet cell hyperplasia, and Smad pathway activation after Ad-TGFβ treatment. Ad-TGFβ produced greater abnormalities in lung mechanics in CF vs control mice, which was uniquely associated with induction of PI3K and MAPK signaling. CFTR transcripts were reduced and ENaC transcripts were increased in CF and non-CF mice, while the goblet cell transcription factors FoxA3 and SPDEF were increased in non-CF but not CF mice following Ad-TGFβ treatment.
CONCLUSION: Pulmonary TGFβ1 expression was sufficient to produce pulmonary remodeling and abnormalities in lung mechanics that were associated with both shared and unique cell signaling pathway activation in CF and non-CF mice. These results highlight the multi-functional impact of TGFβ on pulmonary pathology in vivo and identify cellular response differences that may impact CF lung pathology.

PMID: 29877096 [PubMed - as supplied by publisher]

Combined liver and pancreas transplantation in two children with cystic fibrosis-First experience in Australia and New Zealand.

Pediatr Transplant. 2018 Jun 06;:e13234

Authors: Shankar S, Bolia R, Hodgson A, Bishop JR, Evans HM, Oliver MR

Abstract
We report the first two pediatric patients with CF who underwent successful combined liver-pancreas transplantation in Australia and New Zealand for CF liver disease and CF-related diabetes mellitus.

PMID: 29877025 [PubMed - as supplied by publisher]

Pathogen eradication" and "Emerging pathogens": Difficult definitions in cystic fibrosis.

J Clin Microbiol. 2018 Jun 06;:

Authors: Gilligan PH, Downey DG, Elborn JS, Flume PA, Funk S, Gilpin D, Kidd TJ, McCaughan J, Millar BC, Murphy PG, Rendall JC, Tunney MM, Moore JE

Abstract
Infection is a common complication of cystic fibrosis (CF) airways disease. Current treatment approaches include early intervention with the intent to eradicate pathogens in the hope of delaying development of chronic infection and chronic use of aerosolized antibiotics to suppress infection. The use of molecules that help restore CFTR function, modulate pulmonary inflammation, or improve pulmonary clearance, may also influence the microbial communities in the airways. As the pipeline of these new entities continues to expand, it is important to define when key pathogens are eradicated from the lungs of CF patients and equally important, when new pathogens might emerge as a result of these novel therapies.

PMID: 29875191 [PubMed - as supplied by publisher]

A potential strategy for reducing cysts in autosomal dominant polycystic kidney disease with a CFTR corrector.

J Biol Chem. 2018 Jun 06;:

Authors: Yanda M, Liu Q, Cebotaru L

Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is associated with progressive enlargement of cysts, leading to a decline in function and renal failure that cannot be prevented by current treatments. Mutations in pkd1 and pkd2, encoding the polycystin 1 and 2 proteins, induce growth-related pathways, including heat shock proteins, as occurs in some cancers raising the prospect that pharmacological interventions that target these pathways might alleviate or prevent ADPKD. Here, we demonstrate a role for VX-809, a corrector of cystic fibrosis transmembrane conductance regulator (CFTR) conventionally used to manage cystic fibrosis, in reducing renal cyst growth. VX-809 reduced cyst growth in Pkd1-knockout mice and in proximal tubule-derived, cultured Pkd1-knockout cells. VX-809 reduced both basal and forskolin-activated cAMP levels and also decreased the expression of the adenylyl cyclase AC3, but not of AC6. VX-809 also decreased resting levels of intracellular Ca2+, but did not affect ATP-stimulated Ca2+ release. Notably, VX-809 dramatically decreased thapsigargin-induced release of Ca2+ from the endoplasmic reticulum (ER). VX-809 also reduced levels of the heat shock proteins Hsp27, -70, and -90 in mice cystic kidneys, consistent with restoration of cellular proteostasis. Moreover, VX-809 strongly decreased an ER stress marker, the GADD153 protein, and cell proliferation, but had only a small effect on apoptosis. Given that administration of VX-809 is safe, this drug potentially offers a new way to treat patients with ADPKD.

PMID: 29875161 [PubMed - as supplied by publisher]

Additional important research priorities for bronchiectasis in China.

Eur Respir J. 2017 01;49(1):

Authors: Aliberti S, Dhar R, Aksamit TR, Morgan L, Chalmers JD

PMID: 28100553 [PubMed - indexed for MEDLINE]

De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene.

Brain. 2018 Jun 05;:

Authors: Chemin J, Siquier-Pernet K, Nicouleau M, Barcia G, Ahmad A, Medina-Cano D, Hanein S, Altin N, Hubert L, Bole-Feysot C, Fourage C, Nitschké P, Thevenon J, Rio M, Blanc P, Vidal C, Bahi-Buisson N, Desguerre I, Munnich A, Lyonnet S, Boddaert N, Fassi E, Shinawi M, Zimmerman H, Amiel J, Faivre L, Colleaux L, Lory P, Cantagrel V

Abstract
Cerebellar atrophy is a key neuroradiological finding usually associated with cerebellar ataxia and cognitive development defect in children. Unlike the adult forms, early onset cerebellar atrophies are classically described as mostly autosomal recessive conditions and the exact contribution of de novo mutations to this phenotype has not been assessed. In contrast, recent studies pinpoint the high prevalence of pathogenic de novo mutations in other developmental disorders such as intellectual disability, autism spectrum disorders and epilepsy. Here, we investigated a cohort of 47 patients with early onset cerebellar atrophy and/or hypoplasia using a custom gene panel as well as whole exome sequencing. De novo mutations were identified in 35% of patients while 27% had mutations inherited in an autosomal recessive manner. Understanding if these de novo events act through a loss or a gain of function effect is critical for treatment considerations. To gain a better insight into the disease mechanisms causing these cerebellar defects, we focused on CACNA1G, a gene not yet associated with the early-onset form. This gene encodes the Cav3.1 subunit of T-type calcium channels highly expressed in Purkinje neurons and deep cerebellar nuclei. We identified four patients with de novo CACNA1G mutations. They all display severe motor and cognitive impairment, cerebellar atrophy as well as variable features such as facial dysmorphisms, digital anomalies, microcephaly and epilepsy. Three subjects share a recurrent c.2881G>A/p.Ala961Thr variant while the fourth patient has the c.4591A>G/p.Met1531Val variant. Both mutations drastically impaired channel inactivation properties with significantly slower kinetics (∼5 times) and negatively shifted potential for half-inactivation (>10 mV). In addition, these two mutations increase neuronal firing in a cerebellar nuclear neuron model and promote a larger window current fully inhibited by TTA-P2, a selective T-type channel blocker. This study highlights the prevalence of de novo mutations in early-onset cerebellar atrophy and demonstrates that A961T and M1531V are gain of function mutations. Moreover, it reveals that aberrant activity of Cav3.1 channels can markedly alter brain development and suggests that this condition could be amenable to treatment.

PMID: 29878067 [PubMed - as supplied by publisher]

De Novo DNM1L Variant in a Teenager With Progressive Paroxysmal Dystonia and Lethal Super-refractory Myoclonic Status Epilepticus.

J Child Neurol. 2018 Jan 01;:883073818778203

Authors: Ryan CS, Fine AL, Cohen AL, Schiltz BM, Renaud DL, Wirrell EC, Patterson MC, Boczek NJ, Liu R, Babovic-Vuksanovic D, Chan DC, Payne ET

Abstract
BACKGROUND: The dynamin 1-like gene ( DNM1L) encodes a GTPase that mediates mitochondrial and peroxisomal fission and fusion. We report a new clinical presentation associated with a DNM1L pathogenic variant and review the literature.
RESULTS: A 13-year-old boy with mild developmental delays and paroxysmal dystonia presented acutely with multifocal myoclonic super-refractory status epilepticus. Despite sustained and aggressive treatment, seizures persisted and care was ultimately withdrawn in the context of extensive global cortical atrophy. Rapid trio-whole exome sequencing revealed a de novo heterozygous c.1207C>T (p.R403C) pathogenic variant in DNM1L. Immunofluorescence staining of fibroblast mitochondria revealed abnormally elongated and tubular morphology.
CONCLUSIONS: This case highlights the diagnostic importance of rapid whole exome sequencing within a critical care setting and reveals the expanding phenotypic spectrum associated with DNM1L variants. This now includes progressive paroxysmal dystonia and adolescent-onset super-refractory myoclonic status epilepticus contributing to strikingly rapid and progressive cortical atrophy and death.

PMID: 29877124 [PubMed - as supplied by publisher]

Establishing the role of PLVAP in protein-losing enteropathy: a homozygous missense variant leads to an attenuated phenotype.

J Med Genet. 2018 Jun 06;:

Authors: Kurolap A, Eshach-Adiv O, Gonzaga-Jauregui C, Dolnikov K, Mory A, Paperna T, Hershkovitz T, Overton JD, Kaplan M, Glaser F, Zohar Y, Shuldiner AR, Berger G, Baris HN

Abstract
BACKGROUND: Intestinal integrity is essential for proper nutrient absorption and tissue homeostasis, with damage leading to enteric protein loss, that is, protein-losing enteropathy (PLE). Recently, homozygous nonsense variants in the plasmalemma vesicle-associated protein gene (PLVAP) were reported in two patients with severe congenital PLE. PLVAP is the building block of endothelial cell (EC) fenestral diaphragms; its importance in barrier function is supported by mouse models of Plvap deficiency.
OBJECTIVE: To genetically diagnose two first-degree cousins once removed, who presented with PLE at ages 22 and 2.5 years.
METHODS: Family-based whole exome sequencing was performed based on an autosomal recessive inheritance model. In silico analyses were used to predict variant impact on protein structure and function.
RESULTS: We identified a rare homozygous variant (NM_031310.2:c.101T>C;p.Leu34Pro) in PLVAP, which co-segregated with the disease. Leu34 is predicted to be located in a highly conserved, hydrophobic, α-helical region within the protein's transmembrane domain, suggesting Leu34Pro is likely to disrupt protein function and/or structure. Electron microscopy and PLVAP immunohistochemistry demonstrated apparently normal diaphragm morphology, predicted to be functionally affected.
CONCLUSIONS: Biallelic missense variants in PLVAP can cause an attenuated form of the PLE and hypertriglyceridaemia syndrome. Our findings support the role of PLVAP in the pathophysiology of PLE, expand the phenotypic and mutation spectrums and underscore PLVAP's importance in EC barrier function in the gut.

PMID: 29875123 [PubMed - as supplied by publisher]

Identification of rs7350481 at chromosome 11q23.3 as a novel susceptibility locus for metabolic syndrome in Japanese individuals by an exome-wide association study.

Oncotarget. 2017 Jun 13;8(24):39296-39308

Authors: Yamada Y, Sakuma J, Takeuchi I, Yasukochi Y, Kato K, Oguri M, Fujimaki T, Horibe H, Muramatsu M, Sawabe M, Fujiwara Y, Taniguchi Y, Obuchi S, Kawai H, Shinkai S, Mori S, Arai T, Tanaka M

Abstract
We have performed exome-wide association studies to identify genetic variants that influence body mass index or confer susceptibility to obesity or metabolic syndrome in Japanese. The exome-wide association study for body mass index included 12,890 subjects, and those for obesity and metabolic syndrome included 12,968 subjects (3954 individuals with obesity, 9014 controls) and 6817 subjects (3998 individuals with MetS, 2819 controls), respectively. Exome-wide association studies were performed with Illumina HumanExome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of genotypes of single nucleotide polymorphisms to body mass index was examined by linear regression analysis, and that of allele frequencies of single nucleotide polymorphisms to obesity or metabolic syndrome was evaluated with Fisher's exact test. The exome-wide association studies identified six, 11, and 40 single nucleotide polymorphisms as being significantly associated with body mass index, obesity (P <1.21 × 10-6), or metabolic syndrome (P <1.20 × 10-6), respectively. Subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that three and five single nucleotide polymorphisms were related (P < 0.05) to obesity or metabolic syndrome, respectively, with one of these latter polymorphisms-rs7350481 (C/T) at chromosome 11q23.3-also being significantly (P < 3.13 × 10-4) associated with metabolic syndrome. The polymorphism rs7350481 may thus be a novel susceptibility locus for metabolic syndrome in Japanese. In addition, single nucleotide polymorphisms in three genes (CROT, TSC1, RIN3) and at four loci (ANKK1, ZNF804B, CSRNP3, 17p11.2) were implicated as candidate determinants of obesity and metabolic syndrome, respectively.

PMID: 28445147 [PubMed - indexed for MEDLINE]

Patients' concerns regarding biological agents in rheumatology.

Int J Rheum Dis. 2018 Jun;21(6):1219-1226

Authors: Pehlivan Y, Orucoglu N, Pehlivan S, Kimyon G, Zengin O, Kucuk A, Sahin A, Tomas N, Oksuz MF, Kisacik B, Akar S, Onat AM, Dalkilic E

Abstract
OBJECTIVE: The potential side effects of biological agents may increase the anxiety levels of patients and influence not only their desire to use these therapies but also their concordance to treatment. This study aimed to determine the level and prevalence of drug-related concern in patients treated with biological agents and to acquire additional information regarding the related causes.
MATERIALS AND METHODS: A total of 1134 patients who were using biological agents for at least 3 months with a diagnosis of rheumatic diseases were enrolled. General anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI).
RESULTS: The most common cause for drug-related concerns was the potential side effects of the drugs (59.5%). Among the potential side effects, cancer risk was the most common cause for concern (40.1%), followed by the risk of tuberculosis activation (30.7%). Anxiety levels were higher in patients who experienced side effects than in other patients, and this difference was statistically significant (P < 0.05). STAI trait and state scores were moderately correlated with anxiety levels related to the drug (P < 0.001).
CONCLUSION: Anxiety related to biological agents may significantly affect the patients' anxiety levels. Awareness regarding the patients' concerns and expectations related to the drug is important to ensure drug adherence and concordance to treatment.

PMID: 29879318 [PubMed - in process]

Safe use of vasopressin and angiotensin II for patients with circulatory shock.

Pharmacotherapy. 2018 Jun 07;:

Authors: Bauer SR, Sacha GL, Lam SW

Abstract
Circulatory shock is a medical emergency that requires rapid intervention to optimize patient outcomes. Although catecholamine vasopressors are considered life-sustaining therapy they are associated with adverse reactions and vasopressin and angiotensin II may be utilized to minimize these adverse effects. However, vasopressin and angiotensin II are also associated with adverse reactions that must be known to the clinician in order to mitigate risk for patients. This review focuses on the known adverse drug effects of vasopressin and angiotensin II while offering potential solutions to minimize harm with these agents. Future directions with vasoactive medication safety, including optimization of the electronic medical record, clinical decision support, prediction analytics, and precision medicine for patients with circulatory shock are also discussed. This article is protected by copyright. All rights reserved.

PMID: 29878459 [PubMed - as supplied by publisher]

Cardiovascular Safety of Psychiatric Agents: A Cautionary Tale.

Angiology. 2018 Jan 01;:3319718780145

Authors: Manolis TA, Manolis AA, Manolis AS

Abstract
Psychiatric agents are among the most commonly prescribed medications. Despite the advent of newer generation agents, patients receiving them still experience cardiovascular (CV) side effects. However, these agents may have heterogeneous properties, calling for an individualized approach based on efficacy and also on the particular side effect profile of each specific agent. Proarrhythmic effects arising from drug-induced long-QT syndrome and consequent potentially life-threatening polymorphic ventricular arrhythmias in the form of torsade de pointes, the metabolic syndrome contributing to atherosclerosis and acute coronary syndromes, and drug-induced orthostatic hypotension raise major concerns. Of course, it is also crucial that fear of potential CV adverse effects does not deprive psychiatric patients of appropriate drug therapy. Modification of CV risk factors in psychiatric patients together with optimal management of their CV diseases and appropriate selection of psychotropic agents with greater efficacy and least CV toxicity are of paramount importance in mitigating CV risks and enhancing safety. Identifying patients at high risk of CV complications and close monitoring of all patients receiving these agents are crucial steps to prevent and manage such complications. All these issues are herein reviewed, relevant guidelines are discussed, and schemas are depicted that illustrate the interrelated connections among the psychotropic agents and their CV effects.

PMID: 29874922 [PubMed - as supplied by publisher]

[In process].

Pflege Z. 2017 Apr;70(4):36-8

Authors: Ebbers B

PMID: 29425435 [PubMed - indexed for MEDLINE]