Community pharmacists and their role in pharmacogenomics testing: an Australian perspective drawing on international evidence.

Aust J Prim Health. 2018 Nov 09;:

Authors: Suppiah V, Lim CX, Hotham E

Abstract
Patients obtaining a prescription from a pharmacy expect that the drug will be effective and have minimal side-effects. Unfortunately, drugs exhibit the desired effect in ~25-60% of people prescribed any medication. Adverse effects occur at a rate of 10% in patients taking a medication, and this rate increases during and after hospitalisation, with the transition of care back to the ambulatory setting posing a particular risk. Pharmacogenomics testing has been shown to optimise pharmacotherapy by increasing medication effectiveness and reducing drug-related toxicity, thus curtailing overall healthcare costs. Evidence from international studies have shown that community pharmacists would be able to offer this highly relevant professional service to their clients, given suitable training. This specific training complements pharmacists' existing skills and expertise by educating them in an emerging scientific area of pharmacogenomics. However, in an increasingly tight financial climate, the provision of pharmacogenomics testing by Australian community pharmacists will only be viable with an appropriate reimbursement through the Medicare Benefits Schedule, currently accessible by other allied health practitioners but not by pharmacists.

PMID: 30409245 [PubMed - as supplied by publisher]

Medications With Depression as an Adverse Effect-Reply.

JAMA. 2018 11 06;320(17):1816

Authors: Qato DM, Olfson M

PMID: 30398598 [PubMed - indexed for MEDLINE]

Medications With Depression as an Adverse Effect.

JAMA. 2018 11 06;320(17):1815

Authors: Agustini B, Berk M

PMID: 30398595 [PubMed - indexed for MEDLINE]

Medications With Depression as an Adverse Effect.

JAMA. 2018 11 06;320(17):1815-1816

Authors: Burch PBM

PMID: 30398594 [PubMed - indexed for MEDLINE]

Frequency of Hospitalized Infections Is Reduced in Rheumatoid Arthritis Patients Who Received Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs after 2010.

J Immunol Res. 2018;2018:6259010

Authors: Ichinose K, Shimizu T, Umeda M, Fukui S, Nishino A, Koga T, Kawashiri SY, Iwamoto N, Tamai M, Nakamura H, Sato S, Origuchi T, Kawakami A

Abstract
Background: Biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic (ts) DMARDs are important in rheumatoid arthritis (RA) treatment. The risk of hospitalized infection associated with bDMARDs/tsDMARDs in RA patients is unclear.
Methods: We retrospectively analyzed the cases of the 275 RA patients with 449 treatment episodes who were administered a bDMARD/tsDMARD at Nagasaki University Hospital in July 2003-January 2015. We determined the incidence and risk factors of infection requiring hospitalization in the patients during a 3-year observation period.
Results: Thirty-five (12.7%) of the patients experienced a hospitalized infection. The hospitalized infection risk did not differ significantly among several bDMARDs/tsDMARDs. A multivariate analysis revealed that the comorbidities of chronic lung disease (adjusted HR 5.342, 95% CI 2.409-12.42, p < 0.0001) and the initiation of bDMARDs/tsDMARDs before 2010 (adjusted HR 4.266, 95% CI 1.827-10.60, p = 0.0007) are significant independent risk factors for hospitalized infection. Compared to the before-2010 group, the group of patients whose treatment initiated in 2010 or later showed higher patient ages at the initiation of bDMARD/tsDMARD treatment and a higher rate of the use of prophylaxis with an antituberculosis agent, whereas the disease activities and number of the patients who received >5 mg of prednisolone were lower in the after-2010 group.
Conclusions: This is the first report that the frequency of hospitalized infection significantly decreased when the patients were treated with a bDMARD or tsDMARD after 2010. Our results indicate that the updated announcement of diagnosis and treatment criteria might contribute to a reduced risk of hospitalized infection and a better understanding of the use of bDMARDs/tsDMARDs by rheumatologists.

PMID: 30186881 [PubMed - indexed for MEDLINE]

A case of pembrolizumab-induced localized organizing pneumonia.

Scand J Immunol. 2018 07;88(1):e12677

Authors: Arays R, Wang P

PMID: 29856074 [PubMed - indexed for MEDLINE]

Self-Medication Practice and Associated Factors among Residents in Wuhan, China.

Int J Environ Res Public Health. 2018 01 04;15(1):

Authors: Lei X, Jiang H, Liu C, Ferrier A, Mugavin J

Abstract
BACKGROUND: This study aims to examine the prevalence and predictors associated with self-medication, and related consequences in Wuhan, China.
METHODS: Two-hundred-sixty residents were interviewed from randomly selected four districts of Wuhan, China. A modified version of Anderson's health behavioral model was used in the survey to collect information of self-medication behavior. Multivariable logistic regression analyses were used to measure correlates of the prevalence of self-medication.
RESULTS: Nearly half of the respondents would select self-medication, and 39.1% would see a doctor if they felt sick. The most common self-medicated illnesses were cold and cough, cardiovascular disease and gastrointestinal disease. The main reasons for self-medication were that the illness was not severe (enough) to see the doctor (45%); the patient did not think that the trouble of seeing a doctor was worth the effort (23%); the patient had no time to see the doctor (12%), and the patient did not want to pay high medical costs (15%). Logistic regression results suggested that respondents tended to select self-medication if the illness was minor or short-term (less than seven days).
CONCLUSIONS: Our findings suggest that more strict regulation on over-the-counter medicines may be required to reduce health risks related to self-medication. Targeted health education on the risks of self-medication should be considered.

PMID: 29300318 [PubMed - indexed for MEDLINE]

Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells.

Eur J Immunol. 2018 02;48(2):330-343

Authors: Loeschenberger B, Niess L, Würzner R, Schwelberger H, Eder IE, Puhr M, Guenther J, Troppmair J, Rudnicki M, Neuwirt H

Abstract
One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation.

PMID: 29143318 [PubMed - indexed for MEDLINE]

Skin Necrosis Following Subcutaneous Immunoglobulin (SCIg).

J Clin Immunol. 2017 01;37(1):27-28

Authors: Carne E, Ponsford M, El-Shanawany T, Jolles S

PMID: 27796699 [PubMed - indexed for MEDLINE]

Medicinal cannabis for chemotherapy-induced nausea and vomiting: prescribing with limited evidence.

Med J Aust. 2018 Nov 12;

Authors: Mersiades AJ, Stockler MR, Olver IN, Grimison P

PMID: 30404590 [PubMed - as supplied by publisher]

The combination of levomepromazine (methotrimeprazine) and rotigotine enables the safe and effective management of refractory nausea and vomiting in a patient with idiopathic Parkinson's disease.

Palliat Med. 2018 Nov 08;:269216318809569

Authors: Hindmarsh J, Hindmarsh S, Lee M, Telford R

Abstract
BACKGROUND:: This case report describes a patient with known idiopathic Parkinson's disease, being managed with transdermal rotigotine, whose refractory nausea and vomiting was successfully controlled with subcutaneous levomepromazine. No drug-induced extrapyramidal side effects emerged.
CASE PRESENTATION:: A patient was found to have a locally advanced serous carcinoma, causing secondary bowel obstruction. Furthermore, due to compromised oral access, the patient's oral antiparkinsonian medications for motor control were converted to transdermal rotigotine. Unfortunately, the patient's nausea and vomiting was refractory to a number of recommended antiemetic options.
CASE MANAGEMENT:: Low dose levomepromazine was administered on a, 'when required' basis, via subcutaneous injection.
CASE OUTCOME:: After the first dose of levomepromazine, the patient's nausea and vomiting completely subsided and no extrapyramidal side effects were observed. This was confirmed by daily assessments, revealing no worsening of the motor symptoms associated with idiopathic Parkinson's disease.
CONCLUSIONS:: The pharmacology of rotigotine and levomepromazine appear complementary and may allow for the simultaneous use of both drugs, with favourable outcomes. This case report highlights that rotigotine may afford protection against antipsychotic induced extrapyramidal side effects, while preserving antiemetic effects. Such combinations may have a role in the end-of-life management of idiopathic Parkinson's disease.

PMID: 30404581 [PubMed - as supplied by publisher]

Clinical efficacy and safety of CIK plus radiotherapy for lung cancer: A meta-analysis of 16 randomized controlled trials.

Int Immunopharmacol. 2018 Aug;61:363-375

Authors: Xiao Z, Wang CQ, Zhou MH, Li NN, Liu SY, He YJ, Wang YZ, Feng JH, Yao XS, Chen L, Ma B, Yu S, Zeng XT, Li CW, Ding J

Abstract
OBJECTIVE: Cytokine-induced killer cells (CIK) therapy is the most commonly used cellular immunotherapy. The CIK plus radiotherapy was clinically used in a wide range of treatment, but the efficacy of their combination against lung cancer is not clear yet. Therefore, we systematically evaluated all the related studies to reveal the combination's clinical efficacy and safety in lung cancer.
MATERIALS AND METHODS: We collected all the studies about CIK plus radiotherapy for lung cancer in Medline, Embase, Web of Science (ISI), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang Database, China Biological Medicine Database (CBM) and Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), WHO International Clinical Trials Registry Platform (WHO-ICTRP) and US-clinical trials (March 2017). We evaluated their bias risk according to the Cochrane evaluation handbook of randomized controlled trials (RCTs), extracted all the data, and synthesized the data using meta analysis.
RESULTS: We included 16 RCTs involving 1197 patients with lung cancer, and most trials had unclear risk of bias. Meta-analysis showed that CIK therapy could increase the objective response rate (ORR) (1.32, 1.21 to 1.44), the disease control rate (DCR) (1.13, 1.04 to 1.23), the 1-year overall survival (OS) rate (1.38, 1.16 to 1.63) and the 2-year OS rate (1.23, 1.11 to 1.35). DCs-CIK cells increased the 3-year OS rate (1.66, 1.20 to 2.29). DCs-CIK therapy could increase the CD3+T cells (2.27, 1.47 to 3.06), CD4+T cells (1.28, 0.74 to 1.81), NK cells (2.04, 0.74 to 3.33) and CD4+/CD8+ T cells ratio (1.20, 0.64 to 1.76) and decrease the CD8+T cells (-0.84, -1.60 to -0.08). CIK plus radiotherapy had lower risk of leukopenia (0.85, 0.76 to 0.95) and higher risk of fever (5.50, 2.71 to 11.17) than that of radiotherapy alone. Subgroup analysis showed that CIK plus radiotherapy, mainly three dimensional conformal radiotherapy (3D-CRT) could increase the ORR, DCR, 1- and 2- year OS rate in non-small cell lung cancer (NSCLC), and only DCR in small cell lung cancer (SCLC). Compared with CIK plus pure radiotherapy, except for the ORR, DCR, 1-year OS rate, CIK plus chemoradiotherapy could still increase the 2-year OS rate. DCs-CIK could increase the ORR, DCR, 1- and 2-year OS rate, CIK cells could only increase the ORR and the 1-year OS rate.
CONCLUSIONS: CIK plus radiotherapy can improve the clinical response, OS and PFS in lung cancer. It may have low risk of leukopenia and high risk of fever. CIK plus chemoradiotherapy, mainly 3D-CRT can improve the clinical response, OS and PFS in NSCLC. DCs-CIK cells can improve the 1-, 2- and 3-year OS rate, and the 1- and 2-year PFS rate, and CIK cells only improve the 1-year OS rate. DCs-CIK cells can repair the antitumor immunity.

PMID: 29945024 [PubMed - indexed for MEDLINE]

Prevalence and characteristics of adverse drug events in Brazil.

Cad Saude Publica. 2018 03 29;34(4):e00040017

Authors: Sousa LAO, Fonteles MMF, Monteiro MP, Mengue SS, Bertoldi AD, Pizzol TDSD, Tavares NUL, Oliveira MA, Luiza VL, Ramos LR, Farias MR, Arrais PSD

Abstract
The aim of this study was to describe the prevalence of adverse drug events (ADEs) and associated factors reported by users of medicines in Brazil. This was a cross-sectional population-based study conducted from September 2013 to February 2014 with data from the Brazilian National Survey on Access, Use, and Promotion of Rational Use of Medicines (PNAUM). The study included all individuals that reported the use of medicines and identified, among them, all those reporting at least one problem with the medicine's use. A descriptive analysis was performed to estimate ADE prevalence and 95% confidence intervals (95%CI) among the target variables. Crude and adjusted prevalence ratios were calculated using Poisson regression to investigate factors associated with ADEs. Overall ADE prevalence in Brazil was 6.6% (95%CI: 5.89-7.41), and after multivariate analysis, higher prevalence was associated with female gender, residence in the Central and Northeast regions, consumption of more medicines, "bad" self-rated health, and self-medication. The drugs most frequently reported with ADEs were fluoxetine, diclofenac, and amitriptyline. The most frequent ADEs were somnolence, epigastric pain, and nausea. Most reported ADEs were mild, avoidable, and associated with medicines used frequently by the population. The study provided knowledge on the size of the problem with use of medicines in Brazil.

PMID: 29617479 [PubMed - indexed for MEDLINE]

Genetic variation in human drug-related genes.

Genome Med. 2017 12 22;9(1):117

Authors: Schärfe CPI, Tremmel R, Schwab M, Kohlbacher O, Marks DS

Abstract
BACKGROUND: Variability in drug efficacy and adverse effects are observed in clinical practice. While the extent of genetic variability in classic pharmacokinetic genes is rather well understood, the role of genetic variation in drug targets is typically less studied.
METHODS: Based on 60,706 human exomes from the ExAC dataset, we performed an in-depth computational analysis of the prevalence of functional variants in 806 drug-related genes, including 628 known drug targets. We further computed the likelihood of 1236 FDA-approved drugs to be affected by functional variants in their targets in the whole ExAC population as well as different geographic sub-populations.
RESULTS: We find that most genetic variants in drug-related genes are very rare (f < 0.1%) and thus will likely not be observed in clinical trials. Furthermore, we show that patient risk varies for many drugs and with respect to geographic ancestry. A focused analysis of oncological drug targets indicates that the probability of a patient carrying germline variants in oncological drug targets is, at 44%, high enough to suggest that not only somatic alterations but also germline variants carried over into the tumor genome could affect the response to antineoplastic agents.
CONCLUSIONS: This study indicates that even though many variants are very rare and thus likely not observed in clinical trials, four in five patients are likely to carry a variant with possibly functional effects in a target for commonly prescribed drugs. Such variants could potentially alter drug efficacy.

PMID: 29273096 [PubMed - indexed for MEDLINE]

Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients.

Int J Pharm. 2018 Feb 05;536(2):563-569

Authors: Buckley LA, Salunke S, Thompson K, Baer G, Fegley D, Turner MA

Abstract
A public workshop entitled "Challenges and strategies to facilitate formulation development of pediatric drug products" focused on current status and gaps as well as recommendations for risk-based strategies to support the development of pediatric age-appropriate drug products. Representatives from industry, academia, and regulatory agencies discussed the issues within plenary, panel, and case-study breakout sessions. By enabling practical and meaningful discussion between scientists representing the diversity of involved disciplines (formulators, nonclinical scientists, clinicians, and regulators) and geographies (eg, US, EU), the Excipients Safety workshop session was successful in providing specific and key recommendations for defining paths forward. Leveraging orthogonal sources of data (eg. food industry, agro science), collaborative data sharing, and increased awareness of the existing sources such as the Safety and Toxicity of Excipients for Paediatrics (STEP) database will be important to address the gap in excipients knowledge needed for risk assessment. The importance of defining risk-based approaches to safety assessments for excipients vital to pediatric formulations was emphasized, as was the need for meaningful stakeholder (eg, patient, caregiver) engagement.

PMID: 28729174 [PubMed - indexed for MEDLINE]

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

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