Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial.

PLoS One. 2017;12(2):e0170905

Authors: Elliott LS, Henderson JC, Neradilek MB, Moyer NA, Ashcraft KC, Thirumaran RK

Abstract
BACKGROUND: In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients.
METHODS AND FINDINGS: This prospective, open-label, randomized controlled trial was conducted at one hospital-based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32-1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27-0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31-1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34-0.99; P = 0.045). Differences in composite outcomes at 60 days (exploratory endpoints) were also found. Of the total 124 drug therapy recommendations passed on to clinicians, 96 (77%) were followed. These findings should be verified with additional prospective confirmatory studies involving real-world applications in larger populations to broaden acceptance in routine clinical practice.
CONCLUSIONS: Pharmacogenetic testing of polypharmacy patients aged 50 and older, supported by an appropriate CDST, considerably reduced re-hospitalizations and ED visits at 60 days following enrollment resulting in potential health resource utilization savings and improved healthcare.
TRIAL REGISTRATION: ClinicalTrials.gov NCT02378220.

PMID: 28151991 [PubMed - indexed for MEDLINE]

Postmarketing Safety Events Relating to New Drugs Approved in Brazil Between 2003 and 2013: A Retrospective Cohort Study.

J Clin Pharmacol. 2017 Apr;57(4):493-499

Authors: Botelho SF, Martins MA, Vieira LB, Reis AM

Abstract
This study investigated postmarketing safety events (PMSEs) for new drugs approved in Brazil and evaluated whether a range of drug characteristics influenced the time between approval and the first PMSE. This retrospective study included new drugs registered between 2003 and 2013 by the National Health Surveillance Agency (ANVISA), which is responsible for medicines approval in Brazil. PMSEs were defined as any drug safety alert or drug withdrawal from the market. The existence of risk evaluation and mitigation strategies (REMS) by the US Food and Drug Administration (FDA) and Brazil were recorded. A Kaplan-Meier survival curve of the period between the date of ANVISA registration and the PMSE was calculated. We found a statistically significant difference between the time to PMSE for drugs with an FDA REMS compared with those without a REMS, with a log rank value (Mantel Cox) of 0.002. There was no association between the time to PMSE and the other drug characteristics investigated. This study demonstrated that the frequency of PMSEs for new drugs approved by ANVISA was statistically associated with the existence of an FDA REMS. The time between approval and first PMSE was shorter for drugs with an FDA REMS, and this finding may contribute to improved awareness of the risk/benefit balance required to ensure continued safe and effective use of new drugs.

PMID: 27568487 [PubMed - indexed for MEDLINE]

The principle of safety evaluation in medicinal drug - how can toxicology contribute to drug discovery and development as a multidisciplinary science?

J Toxicol Sci. 2016;41(Special):SP49-SP67

Authors: Horii I

Abstract
Pharmaceutical (drug) safety assessment covers a diverse science-field in the drug discovery and development including the post-approval and post-marketing phases in order to evaluate safety and risk management. The principle in toxicological science is to be placed on both of pure and applied sciences that are derived from past/present scientific knowledge and coming new science and technology. In general, adverse drug reactions are presented as "biological responses to foreign substances." This is the basic concept of thinking about the manifestation of adverse drug reactions. Whether or not toxic expressions are extensions of the pharmacological effect, adverse drug reactions as seen from molecular targets are captured in the category of "on-target" or "off-target", and are normally expressed as a biological defense reaction. Accordingly, reactions induced by pharmaceuticals can be broadly said to be defensive reactions. Recent molecular biological conception is in line with the new, remarkable scientific and technological developments in the medical and pharmaceutical areas, and the viewpoints in the field of toxicology have shown that they are approaching toward the same direction as well. This paper refers to the basic concept of pharmaceutical toxicology, the differences for safety assessment in each stage of drug discovery and development, regulatory submission, and the concept of scientific considerations for risk assessment and management from the viewpoint of "how can multidisciplinary toxicology contribute to innovative drug discovery and development?" And also realistic translational research from preclinical to clinical application is required to have a significant risk management in post market by utilizing whole scientific data derived from basic and applied scientific research works. In addition, the significance for employing the systems toxicology based on AOP (Adverse Outcome Pathway) analysis is introduced, and coming challenges on precision medicine are to be addressed for the new aspect of efficacy and safety evaluation.

PMID: 28250284 [PubMed - indexed for MEDLINE]

14 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 2017/08/15

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.

Pharmacovigilance Skills, Knowledge and Attitudes in our Future Doctors - A Nationwide Study in the Netherlands.

Basic Clin Pharmacol Toxicol. 2017 May;120(5):475-481

Authors: Schutte T, Tichelaar J, Reumerman MO, van Eekeren R, Rissmann R, Kramers C, Richir MC, van Puijenbroek EP, van Agtmael MA, Education Committee/Working Group Research in Education of the Dutch Society of Clinical Pharmacology and Biopharmacy (NVKF&B), Utrecht, The Netherlands

Abstract
Pharmacovigilance centres monitor the safety of drugs, based on adverse drug reactions (ADRs) reported by doctors, pharmacists and pharmaceutical companies. However, the under-reporting of ADRs remains a major problem. Our aim was to investigate preparedness of future doctors for their role in pharmacovigilance, by assessing their pharmacovigilance awareness, skills and knowledge. The study was a nationwide e-survey among medical students (third to sixth year) of all eight medical schools in the Netherlands. The survey consisted of questions regarding pharmacovigilance awareness, skills and knowledge. Overall, 874 students provided informed consent and participated (response 12%). Almost all students (96%) intended to report serious ADRs in their future practice. Almost half (44%) of the students did not know where to report an ADR, and 78% did not know which items were necessary for a good-quality ADR report. While more than 78% of the students agreed that pharmacovigilance is an important topic in their medical education, only 26% found that their current curriculum covered pharmacovigilance adequately. Although ADR reporting is considered relevant and important among future doctors, many do not know where and what to report. This is highly undesirable and should have consequences for pharmacotherapy teaching.

PMID: 27883270 [PubMed - indexed for MEDLINE]

The Effect of Pharmacist-led Psychiatric Pharmacotherapy Conferences on the Appropriate Use of Antipsychotics.

Yakugaku Zasshi. 2017;137(5):603-610

Authors: Sano T, Inoue M, Takizawa M, Shimamori Y, Kurosawa N

Abstract
　The Hakodate Watanabe Hospital has held pharmacist-led multidisciplinary psychiatric pharmacotherapy conferences since September 2013 in order to optimize pharmacotherapy. The effects of holding regular conferences on the correction of high-dose antipsychotic polypharmacy, prevention and reduction of adverse reactions to antipsychotics, and reduction of the drug costs were investigated in psychiatric inpatients prescribed 4 or more antipsychotics. The results revealed that the number of antipsychotics and number of all drugs were significantly reduced by 1, the chlorpromazine (CP)-equivalent dose was significantly reduced by approximately 350 mg, and the drug costs were significantly reduced by 176.5 yen/d. In regard to the effects on the laboratory test data, the blood glucose and hemoglobin A1c (HbA1c) levels were significantly reduced. In addition, 84.8% of the patients were assessed as "unchanged" using the Clinical Global Impression of Change (CGI-C), indicating the absence of any significant changes in the severity of the clinical psychiatric symptoms. The results confirm that psychiatric pharmacotherapy conferences are effective for promoting appropriate use of antipsychotics, reducing the incidence of metabolic adverse reactions, such as elevation of the blood glucose, and also reducing the drug costs. The above results suggest that psychiatric pharmacotherapy conferences encourage psychiatric medical teams to adjust prescriptions while sharing information, and are effective for optimizing pharmacotherapy.

PMID: 28458292 [PubMed - indexed for MEDLINE]

[Levodopa-carbidopa intestinal gel in the treatment of patients with Parkinson disease: results of a 12-month open study].

Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(2):22-31

Authors: Skoromets AA, Odinak MM, Yakupov EZ, Litvinenko IV, Zalyalova ZA, Timofeeva AA, Kirtaev SY, Bogdanov RR, Agafina AS, Chatamra K, Robieson W, Benesh J, Latypova GR, Ershova MV, Illarioshkin SN

Abstract
AIM: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs.
MATERIAL AND METHODS: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study.
RESULTS: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study.
CONCLUSION: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.

PMID: 28374689 [PubMed - indexed for MEDLINE]

Naringin Ameliorates HIV-1 Nucleoside Reverse Transcriptase Inhibitors- Induced Mitochondrial Toxicity.

Curr HIV Res. 2016;14(6):506-516

Authors: Oluwafeyisetan A, Olubunmi A, Peter O

Abstract
BACKGROUND: Mitochondrial reactive oxygen species (ROS) generation and defective oxidative phosphorylation (OXPHOS) have been proposed as possible mechanisms underlying the development of nucleoside reverse transcriptase inhibitors (NRTIs)-induced mitochondrial toxicities. Available options in managing these complications have, so far, produced controversial results, thus necessitating further research into newer agents with promise. Antioxidant and free-radical scavenging effects of naringin, a plant-derived flavonoid, have previously been demonstrated.
OBJECTIVE: This study was designed to investigate the effects of naringin on NRTIs-induced mitochondrial toxicity.
METHODS: Wistar rats were randomly divided into Zidovudine (AZT)-only (100 mg/kg body weight BW); AZT+Naringin (100+50 mg/kg BW); AZT+Vitamin E (100+100 mg/kg BW); Stavudine (d4T)- only (50 mg/kg BW); d4T+Naringin (50+50 mg/kg BW); d4T+Vitamin E (50+100 mg/kg BW) and Vehicle (3.0 mL/kg BW)-treated groups, respectively. After 56 days of oral daily dosing, rats were euthanized by halothane overdose, blood collected by cardiac puncture and livers promptly excised for further biochemical and ultrastructural analyses. &lt;/p&gt; Results: AZT- or d4T-only caused significant mitochondrial dysfunction and mitochondrial ultrastructural damage compared to controls, while either naringin or vitamin E reversed indices of mitochondrial dysfunction evidenced by significantly reduced mitochondrial malondialdehyde (MDA) and blood lactate concentrations, increased liver manganese superoxide dismutase (MnSOD) activity and upregulate expression of mitochondrial-encoded subunit of electron transport chain (ETC) complex IV protein compared to AZT- or d4T-only treated rats. Furthermore, naringin or vitamin E, respectively, ameliorated mitochondrial damage observed in AZT- or d4T-only treated rats.
CONCLUSION: Naringin ameliorated oxidative stress and NRTI-induced mitochondrial damage and might, therefore, be beneficial in managing toxicities and complications arising from NRTI use.

PMID: 27197616 [PubMed - indexed for MEDLINE]

Medication Complexity, Medication Number, and Their Relationships to Medication Discrepancies.

Ann Pharmacother. 2016 Jul;50(7):534-40

Authors: Patel CH, Zimmerman KM, Fonda JR, Linsky A

Abstract
BACKGROUND: Medication reconciliation to identify discrepancies is a National Patient Safety Goal. Increasing medication number and complex medication regimens are associated with discrepancies, nonadherence, and adverse events. The Medication Regimen Complexity Index (MRCI) integrates information about dosage form, dosing frequency, and additional directions.
OBJECTIVE: This study evaluates the association of MRCI scores and medication number with medication discrepancies and commissions, a discrepancy subtype.
METHODS: This was a retrospective cohort study of a convenience sample of 104 ambulatory care patients seen from April 2010 to July 2011 within the Department of Veterans Affairs. Primary outcomes included any medication discrepancy and commissions. Primary exposures included MRCI scores and medication number. Multivariable logistic regression models associated MRCI scores and medication number with discrepancies. Receiver operating characteristic (ROC) curves provided discrepancy thresholds.
RESULTS: For the 104 patients analyzed, the median MRCI score was 25 (interquartile range [IQR] = 14-43), and the median medication number was 8 (IQR = 5-13); 60% of patients had any discrepancy, whereas 36% had a commission. In adjusted analyses, patients with MRCI scores ≥25 or medication number ≥8 were more likely to have commissions (odds ratio [OR] = 3.64, 95% CI = 1.41-9.41; OR = 4.51, 95% CI = 1.73-11.73, respectively). The unadjusted ROC threshold for commissions was 36 for MRCI (sensitivity, 59%; specificity, 82%) and 9 for medication number (sensitivity 68%; specificity 67%).
CONCLUSION: Patients with either MRCI scores ≥25 or ≥8 medications were more likely to have commissions. Given equal performance in predicting discrepancies, the efficiency and simplicity of medication number supports its use in identifying patients for intensive medication review beyond medication reconciliation.

PMID: 27147704 [PubMed - indexed for MEDLINE]

Potentially Inappropriate Medications in Older Adults: Why the Revised Criteria Matter.

Ann Pharmacother. 2016 Jul;50(7):599-603

Authors: Barenholtz Levy H, Marcus EL

Abstract
The 2 most widely used explicit criteria regarding inappropriate medication use in older adults are the American Geriatrics Society's Beers Criteria and the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START). Both documents were updated recently. They are important educational tools that highlight medications for which risks of use may often exceed benefits in older adults and situations in which potentially appropriate medications should be considered for use. The application of these tools has the potential to significantly affect patient care. Thus, it is important for clinicians to be familiar with both documents.

PMID: 27083921 [PubMed - indexed for MEDLINE]

13 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 2017/08/10

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.

How Common Are Pulmonary and Hepatic Adverse Effects in Older Adults Prescribed Nitrofurantoin?

J Am Geriatr Soc. 2017 Jun;65(6):1316-1320

Authors: Claussen K, Stocks E, Bhat D, Fish J, Rubin CD

Abstract
OBJECTIVES: To determine the frequency of serious pulmonary and hepatic adverse events (AEs) in persons aged 65 and older prescribed nitrofurantoin.
DESIGN: Retrospective electronic health record (EHR) audit of nitrofurantoin prescriptions and associated AEs.
SETTING: Urban academic medical center.
PARTICIPANTS: All inpatients and outpatients aged 65 and older prescribed nitrofurantoin from January 1, 2010, to December 31, 2014.
MEASUREMENTS: The number of nitrofurantoin prescriptions and pulmonary and hepatic AEs associated with nitrofurantoin use was acquired by data extraction from EHRs.
RESULTS: Of 3,400 individuals aged 65 and older prescribed nitrofurantoin during the study period, 641 were identified as possibly having one of five targeted symptoms or disease complications (pulmonary and hepatic) associated with nitrofurantoin. After a detailed chart audit, 89% were deemed to have no adverse reaction, 7% had a minor side effect or allergy, and 3.9% met criteria for suspicion of a nitrofurantoin-induced AE, five of whom were rated as being highly suspicious for nitrofurantoin toxicity; four of the five were identified with pulmonary toxicity and one with hepatotoxicity. Four of five of these individuals used nitrofurantoin chronically.
CONCLUSION: Nitrofurantoin was prescribed for 3,400 individuals aged 65 and older during the 5-year study period. Serious side effects appeared to be uncommon, but chronic use appeared to be at greater risk.

PMID: 28306135 [PubMed - indexed for MEDLINE]

Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review.

J Antimicrob Chemother. 2016 Oct;71(10):2754-9

Authors: Jenkins A, Thomson AH, Brown NM, Semple Y, Sluman C, MacGowan A, Lovering AM, Wiffen PJ, (BSAC Working Party on Therapeutic Drug Monitoring)

Abstract
OBJECTIVES: The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity.
METHODS: A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion.
RESULTS: Seventeen studies for inclusion were identified, comprising 1677 participants. Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only 11 papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 to 40 mg/L and target troughs were typically <10 or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing; troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in 12 and 8 studies.
CONCLUSIONS: This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximize therapeutic outcomes and minimize toxicity with amikacin.

PMID: 27494904 [PubMed - indexed for MEDLINE]

CSF-1R-Dependent Lethal Hepatotoxicity When Agonistic CD40 Antibody Is Given before but Not after Chemotherapy.

J Immunol. 2016 Jul 01;197(1):179-87

Authors: Byrne KT, Leisenring NH, Bajor DL, Vonderheide RH

Abstract
Cancer immunotherapies are increasingly effective in the clinic, especially immune checkpoint blockade delivered to patients who have T cell-infiltrated tumors. Agonistic CD40 mAb promotes stromal degradation and, in combination with chemotherapy, drives T cell infiltration and de novo responses against tumors, rendering resistant tumors susceptible to current immunotherapies. Partnering anti-CD40 with different treatments is an attractive approach for the next phase of cancer immunotherapies, with a number of clinical trials using anti-CD40 combinations ongoing, but the optimal therapeutic regimens with anti-CD40 are not well understood. Pancreatic ductal adenocarcinoma (PDA) is classically resistant to immunotherapy and lacks baseline T cell infiltration. In this study, we used a tumor cell line derived from a genetically engineered mouse model of PDA to investigate alterations in the sequence of anti-CD40 and chemotherapy as an approach to enhance pharmacological delivery of chemotherapy. Unexpectedly, despite our previous studies showing anti-CD40 treatment after chemotherapy is safe in both mice and patients with PDA, we report in this article that anti-CD40 administration <3 d in advance of chemotherapy is lethal in more than half of treated C57BL/6 mice. Anti-CD40 treatment 2 or 3 d before chemotherapy resulted in significantly increased populations of both activated myeloid cells and macrophages and lethal hepatotoxicity. Liver damage was fully abrogated when macrophage activation was blocked using anti-CSF-1R mAb. These studies highlight the dual nature of CD40 in activating both macrophages and T cell responses, and the need for preclinical investigation of optimal anti-CD40 treatment regimens for safe design of clinical trials.

PMID: 27217585 [PubMed - indexed for MEDLINE]

Health regulatory communications of well-established safety-related pharmacogenomics associations in six developed countries: an evaluation of alignment.

Pharmacogenomics J. 2017 Mar;17(2):121-127

Authors: Tan-Koi WC, Lim ES, Teo YY

Abstract
Recommendations on genetic testing are typically conveyed by drug regulatory authorities through drug labels, which are legal requirements for market authorization of drugs. We conducted a cross-sectional study of drug labels focusing on three crucial aspects of regulatory pharmacogenomics communications: (i) intent; (ii) interpretation in the local context; and (iii) implications of the genetic information. Labels of drugs associated with well-established safety-related genetic markers for adverse drug reactions across six developed countries of United States, Canada, United Kingdom, Australia, New Zealand and Singapore were reviewed. We found differing medical advice for genotype-positive HLA-B*15:02, HLA-A*31:01, UGT1A1*28 and CYP2D6 ultra-rapid metabolisers in breastfeeding women. This raises questions on implications to clinical practice between these countries. Varying ways of presenting at-risk population and allele frequencies also raises question in incorporating such information in drug labels. An international guidance addressing these crucial aspects of regulatory pharmacogenomic communications in drug labels is long overdue.

PMID: 26902540 [PubMed - indexed for MEDLINE]

19 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 2017/08/08

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.

21 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 2017/08/08

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.

Evidence and decision algorithm for the withdrawal of antipsychotic treatment in the elderly with dementia and neuropsychiatric symptoms.

Eur J Clin Pharmacol. 2017 Aug 05;:

Authors: Miarons M, Cabib C, Barón FJ, Rofes L

Abstract
PURPOSE: Antipsychotics (APs) are commonly used to manage neuropsychiatric symptoms (NPS) in elderly patients with dementia, even though several large studies have demonstrated an association between AP treatment and increased morbidity and mortality in people with dementia. The aim of this study is to review the scientific literature of the use of AP in the elderly with dementia and to propose an algorithm to assist in decision-making regarding the withdrawal of APs.
METHODS: A computerized literature search (MEDLINE: 1966 to December 2016, EMBASE: 1982 to December 2016) was used to locate relevant literature. Keywords in the search included terms from Medical Subject Headings (MESH) and EMBASE thesaurus (EMTREE). The following terms were used in the MESH database and EMTREE thesaurus: Aged, Antipsychotic Agents, Behavioral Symptoms and Dementia.
RESULTS: Earlier studies of APs used in elderly patients with dementia suggest that, in most elderly demented patients, APs can be withdrawn with no effect on behaviour. These patients are likely to benefit from the algorithm we propose to assist clinicians in the withdrawal of APs.
CONCLUSIONS: In this paper, we review the potential risks and benefits of discontinuing AP treatment in elderly demented patients with NPS and propose an algorithm to assist in decision-making regarding AP withdrawal.

PMID: 28780696 [PubMed - as supplied by publisher]

[Comparative relevance of declaration of side effects by patients and health professionals].

Therapie. 2017 Jul 08;:

Authors: Lagneau A, Vigier C, Marianna A, Serfaty R, Rocher F, Spreux A, Drici MD

Abstract
INTRODUCTION: Drug-induced adverse events have been accessible to patient's spontaneous reporting in France and such notifications have been steadily increasing since 2011. However, these notifications are still shrouded with medical perplexity and are sometimes subjected to partial caution in their interpretation by the patient's physician. We aimed to evaluate and compare prospectively the relevance of such spontaneous notifications with those provided by healthcare professionals to the French Pharmacovigilance Center of Nice-Alpes-Côte d'Azur.
METHODS: Spontaneous reporting of drug adverse events notified by patients and health care professionals were compared in terms of critical (name, date, effect, drug involved, chronological compatibility) and non-critical (posology, dosage) information, whereas the plausibility of the cases were assessed in weekly multispecialty staffs. Each patient's notification was matched with the immediate pre- and post-notifications declared by health care providers.
RESULTS: Spontaneous notifications from 61 patients were compared with 122 notifications from health care providers. Neither the critical information necessary for declaring the case in the national database (7/61 versus 16/122, P=0.75), nor the uncritical elements allowing to assess the case (30/61 versus 51/122, P=0.22), its plausibility or the causality of the drug (P=0.10) differed significantly between the two groups. 107 cases out of 122 (88%) notified by health care providers were classified as serious, as compared with 19 out of 61 (15%) of patient's ones (P<0.001).
CONCLUSION: Despite concerns from pharmacovigilance specialists in France, the medical relevance of spontaneous reported drug-associated adverse events does not differ from that of health care providers.

PMID: 28780021 [PubMed - as supplied by publisher]

Effect of renal function on antihypertensive drug safety and efficacy in children.

Pediatr Nephrol. 2017 Aug 04;:

Authors: Watt KM, Avant D, Sherwin J, Benjamin DK, Hornik C, Benjamin DK, Li JS, Smith PB

Abstract
BACKGROUND: Hypertension and chronic kidney disease (CKD) are common comorbidities. Guidelines recommend treating hypertension in children with CKD because it is a modifiable risk factor for subsequent cardiovascular disease. Children with CKD are frequently excluded from antihypertensive drug trials. Consequently, safety and efficacy data for antihypertensive drugs are lacking in children with CKD.
METHODS: We determined the incidence of adverse events in 10 pediatric antihypertensive trials to determine the effect of renal function on antihypertensive safety and efficacy in children. These trials were submitted to the US Food and Drug Administration from 1998 to 2005. We determined the number and type of adverse events reported during the trials and compared these numbers in participants with normal renal function and those with decreased function (defined as an estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m(2) calculated using the original Schwartz equation).
RESULTS: Among the 1,703 children in the 10 studies, 315 had decreased renal function. We observed no difference between the two cohorts in the incidence of adverse events or adverse drug reactions related to study drug. Only 5 participants, all with decreased renal function, experienced a serious adverse event; none was recorded by investigators to be study drug-related. Among treated participants, children with decreased renal function who received a high dose of study drug had a significantly larger drop in diastolic blood pressure compared with children with normal renal function.
CONCLUSIONS: These data show that antihypertensive treatment in children with renal dysfunction can be safe and efficacious, and consideration should be given to their inclusion in selected drug development programs.

PMID: 28779238 [PubMed - as supplied by publisher]