Benefits, benefits, once more benefits... with no risk? Stop overlooking the harms of medicines.

Eur J Clin Pharmacol. 2018 Mar;74(3):373-375

Authors: Garattini S, Bertele' V

Abstract
Consideration of drug benefits and harms is asymmetric. Approval of drugs is mainly based on efficacy, while the assessment of their safety is left to post-marketing commitments or spontaneous reporting. Benefits are overestimated as a result of pharmaceutical companies' advertisements, the paucity of independent information, and the scant understanding of the effectiveness of medicines in real life. Polypharmacy in older adults-even during the last period of their life-reflects the tendency to assign priority to efficacy and overlook harms, although nobody knows what happens when three or more drugs are given chronically. Medical journals and public research funding projects do not pay enough attention to drug toxicity. We call for a sense of purpose by all those involved in medicine to tackle this problem. European and national agencies and health authorities should promote and support independent information and experimental and clinical studies on drug toxicity. Information should rely not just on spontaneous reporting but also on active pharmacovigilance. The benefit-harm profile of drugs should be periodically reviewed in the light of toxic effects that come to light over the years. Potential interactions within polytherapies should be sought by re-assessing the pharmacokinetics and pharmacodynamics of their components.

PMID: 29181699 [PubMed - indexed for MEDLINE]

Longitudinal patterns of potentially inappropriate prescribing in early old-aged people.

Eur J Clin Pharmacol. 2018 Mar;74(3):307-313

Authors: Hansen CR, Byrne S, Cullinan S, O'Mahony D, Sahm LJ, Kearney PM

Abstract
PURPOSE: It is contentious whether potentially inappropriate prescribing (PIP) is predominantly a phenomenon of late life or whether it has its origins in early old age. This study examined the pattern of PIP in an early old-aged population over 5 years.
METHODS: Secondary data analysis of a population-based primary care cohort, of patients aged 60-74 years. Medication data were extracted from electronic patient records in addition to information on comorbidities and demographics. Explicit START criteria (PPOs) and STOPP criteria (PIMs) were used to identify PIP. Generalised estimating equations were used to describe trends in PIP over time and adjusted for age, gender and number of medicines.
RESULTS: A total of 978 participants (47.8%) aged 60-74 years were included from the cohort. At baseline, PPOs were detected in 31.2% of patients and PIMs were identified in 35.6% at baseline. Prevalence of PPOs and PIMs increased significantly over time (OR 1.08, 95% CI 1.07; 1.09 and OR 1.04, 95% CI 1.0; 1.06, respectively). A higher number of medicines and new diagnoses were associated with the increasing trend in both PPO and PIM prevalence observed over time, independent of PPOs and PIMs triggered by drug combinations.
CONCLUSIONS: Potentially inappropriate prescribing is highly prevalent among early old-aged people in primary care and increases as they progress to more advanced old age, suggesting that routine application of STOPP/START criteria in this population would significantly improve medication appropriateness.

PMID: 29177646 [PubMed - indexed for MEDLINE]

Inter-rater reliability of STOPPFrail [Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy] criteria amongst 12 physicians.

Eur J Clin Pharmacol. 2018 Mar;74(3):331-338

Authors: Lavan AH, Gallagher P, O'Mahony D

Abstract
PURPOSE: STOPPFrail is an explicit tool, developed by Delphi consensus, to assist physicians with deprescribing medications in frail older adults with poor survival prognosis. This study aimed to determine the inter-rater reliability (IRR), amongst physicians, of STOPPFrail application.
METHODS: Twenty clinical cases were collated to represent frail older patients. Eighteen cases met STOPPFrail inclusion criteria. They had a mean age of 79.5 (SD6) years and a median of 7 (IQR6-8.25) comorbidities and were prescribed a median of 9 (IQR7.75-11.25) medications. Two of the STOPPFrail originators reached complete agreement (gold standard) in determining 91 of 165 medications (55.2%) as inappropriate. Twelve physicians (6 geriatricians, 3 general practitioners and 3 palliative care physicians) independently applied STOPPFrail criteria. IRR between physicians and gold standard (GS) assessment was determined using Cohen's kappa statistic.
RESULTS: Eighteen of the 20 cases that met STOPPFrail inclusion criteria were correctly identified by 9 of 12 physicians (75%). The average time taken per clinical case was 2.7 (SD0.94) minutes. The kappa co-efficient between physicians and GS assessment ranged from 0.71 (substantial) to 0.86 (good), with a mean kappa value of 0.758 (SD0.059). The Fleiss kappa coefficients between GS assessment and geriatricians, GPs and palliative care physicians were 0.80 (SD0.6), 0.77 (SD0.9) and 0.75 (SD0.1), respectively. No significant difference was noted, between groups or between participants within groups, as determined by one-way ANOVA, (df (2, 9) = 0.712, p = 0.516).
CONCLUSIONS: IRR of STOPPFrail criteria between physicians, practising in different specialties, is substantial, despite no prior knowledge of the criteria.

PMID: 29159488 [PubMed - indexed for MEDLINE]

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New insight into organic anion transporters from the perspective of potentially important interactions and drugs toxicity.

J Physiol Pharmacol. 2018 Jun;69(3):

Authors: Mor AL, Kaminski TW, Karbowska M, Pawlak D

Abstract
The family of organic anion transporters (OATs) includes a group of over 10 transmembrane transporting proteins belonging to the solute carrier 22 subfamilies of the major facilitator superfamily. Their function is related to the transport of a great variety of organic anions against the electrical and chemical gradient. OATs are present in most types of human tissues, including the kidneys, liver, placenta, olfactory epithelium, retina, and choroid plexus tissues. The OATs family plays an important role in the cellular uptake, distribution, excretion, and detoxification of many water-soluble drugs, endogenous compounds, nutrition ingredients, environmental contaminants and toxins, and significantly impacts their efficacy, pharmacokinetics and toxicity, both in a preferable and unfavorable way. OATs demonstrated great potential to participate in many potentially relevant interactions, which may lead to unexpected, but not always detrimental, effects. Wider knowledge about their specific functions in the body, role in disease states, pharmacokinetics interactions, and intraindividual response to therapeutic treatment will allow to predict and prevent OAT-related adverse effects or use favorable interactions in pharmacotherapy, as well as to rationally design therapeutics targeted at individual transporter drugs with improved bioavailability, prolonged half-life or reduced toxicity, and improve safety guidelines concerning drug dosage. This review gathers recent reports regarding OAT-related essential interactions involving components of popular therapeutic herbal products, dietary supplements, and clinically important drugs, their significance and potential suitability in modulating the severity of drug-related side effects and toxicity mechanisms.

PMID: 30149367 [PubMed - in process]

Data-Driven Assessment of Potentially Inappropriate Medication in the Elderly.

Stud Health Technol Inform. 2018;253:125-129

Authors: Friedrichs M, Shoshi A, Kleine M

Abstract
Multimorbid patients taking polypharmacy represent a growing population at high risk for inappropriate prescribing. Various lists for identifying potentially inappropriate medication are spread across scientific journals and difficult to access. To address this ongoing need, a new database named PIMBase is developed which integrates these well-known lists and unifies their rating scales. The analysis of the pharmacovigilance data reveals the benefits of combining the lists. PIMBase is meant to be a web-based system and starting point for the data-driven assessment of polypharmacy to identify inappropriate medication and to improve the quality of prescribing. PIMBase is available at https://pimbase.kalis-amts.de.

PMID: 30147056 [PubMed - in process]

Detection and analysis of drug-drug interactions among hospitalized cardiac patients in the Mohammed V Military Teaching Hospital in Morocco.

Pan Afr Med J. 2018;29:225

Authors: Fettah H, Moutaouakkil Y, Sefrioui MR, Moukafih B, Bousliman Y, Bennana A, Lamsaouri J, Makram S, Cherrah Y

Abstract
Introduction: Drug-drug interactions (DDIs) are defined as two or more drugs interacting in such a manner that the effectiveness or toxicity of one or more drugs is altered. Patients with cardiovascular disorders are at higher risk for DDIs because of the types and number of drugs they receive. The aim of the present study was to assess the prevalence of DDIs in patients admitted to the cardiology department of a hospital in Morocco.
Methods: A prospective observational study from June 2016 to September 2016 was carried out in the cardiology department of a hospital in Morocco. Those patients who were taking at least two drugs and had a hospital stay of at least 48 hours were included in the study. The medications of the patients were analysed for possible interactions. All the prescriptions of the study population were screened for drug-drug interactions using a computerized DDI database system (Theriaque®).
Results: During the study period, 138 patients were included; 360 interactions were detected among 94 patients, with an average number of drugs taken of 5.2. The prevalence of DDIs was estimated at 68.11%, the most common of which concerned Kardegic/Plavix (12.22%), Kardegic/Heparin (8.33%), and Lasilix/Spironolactone (5.83%). Among the 726 prescribed drugs, (372 [51.24%]) were drugs of the cardiovascular system, followed by blood and hematopoietic organ drugs (288 [39.67%]) according to the Anatomical Therapeutic Chemical Classification codes. These interactions were categorized on the basis of level of severity: interactions with major severity accounted for 11.11% (40) of the total DDIs while those with moderate and minor severity accounted for 37.22% (134) and 51.66% (186), respectively.
Conclusion: This study reports the prevalence of DDIs in patients admitted to the cardiology department of a hospital in Morocco. This study shows that DDIs are frequent among hospitalized cardiac patients and highlights the need to screen prescriptions of cardiovascular patients for possible DDIs, as this helps in their detection and prevention.Pan African Medical Journal - ISSN: 1937- 8688 (www.panafrican-med-journal.com)Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net)Pan African Medical Journal - ISSN: 1937- 8688 (www.panafrican-med-journal.com)Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net).

PMID: 30100979 [PubMed - indexed for MEDLINE]

Creating and evaluating an opportunity for medication reconciliation in the adult population of South Africa to improve patient care.

Hosp Pract (1995). 2018 Aug;46(3):110-120

Authors: Naicker P, Schellack N, Godman B, Bronkhorst E

Abstract
OBJECTIVE: Adverse drug events (ADEs) are a major cause of morbidity and mortality, with more than 50% of ADEs being preventable. Adverse Drug Reactions (ADRs) are typically the result of an incomplete medication history, prescribing or dispensing error, as well as over- or under-use of prescribed pharmacotherapy. Medication reconciliation is the process of creating the most accurate list of medications a patient is taking and subsequently comparing the list against the different transitions of care. It is used to reduce medication discrepancies, and thereby ultimately decreasing ADEs. However, little is known about medicine reconciliation activities among public hospitals in South Africa.
METHODS: Prospective quantitative, descriptive design among Internal and Surgical wards in a leading public hospital in South Africa.
RESULTS: 145 study participants were enrolled. Over 1300 (1329) medicines were reviewed of which there was a significant difference (p = 0.006) when comparing the medications that the patient was taking before or during hospitalisation. A total of 552 (41.53%) interventions were undertaken and the majority of patients had at least 3.96 medication discrepancies. The most common intervention upon admission was transcribing the home medication onto the hospital prescription (65.2%) followed by medication duplication (13.44%). During patient's hospital stay, interventions included patient counselling (32.5%) and stopping the previous treatment (37.5%).
CONCLUSION: To ensure continuity of patient care, medication reconciliation should be implemented throughout patients' hospital stay. This involves all key professionals in hospitals.

PMID: 29619837 [PubMed - indexed for MEDLINE]

AOP-DB: A database resource for the exploration of Adverse Outcome Pathways through integrated association networks.

Toxicol Appl Pharmacol. 2018 03 15;343:71-83

Authors: Pittman ME, Edwards SW, Ives C, Mortensen HM

Abstract
The Adverse Outcome Pathway (AOP) framework describes the progression of a toxicity pathway from molecular perturbation to population-level outcome in a series of measurable, mechanistic responses. The controlled, computer-readable vocabulary that defines an AOP has the ability to, automatically and on a large scale, integrate AOP knowledge with publically available sources of biological high-throughput data and its derived associations. To support the discovery and development of putative (existing) and potential AOPs, we introduce the AOP-DB, an exploratory database resource that aggregates association relationships between genes and their related chemicals, diseases, pathways, species orthology information, ontologies, and gene interactions. These associations are mined from publically available annotation databases and are integrated with the AOP information centralized in the AOP-Wiki, allowing for the automatic characterization of both putative and potential AOPs in the context of multiple areas of biological information, referred to here as "biological entities". The AOP-DB acts as a hypothesis-generation tool for the expansion of putative AOPs, as well as the characterization of potential AOPs, through the creation of association networks across these biological entities. Finally, the AOP-DB provides a useful interface between the AOP framework and existing chemical screening and prioritization efforts by the US Environmental Protection Agency.

PMID: 29454060 [PubMed - indexed for MEDLINE]

Prevalence and Management of Drug-Related Problems in Chronic Kidney Disease Patients by Severity Level: A Subanalysis of a Cluster Randomized Controlled Trial in Community Pharmacies.

J Manag Care Spec Pharm. 2018 Feb;24(2):173-181

Authors: Quintana-Bárcena P, Lord A, Lizotte A, Berbiche D, Lalonde L

Abstract
BACKGROUND: Drug-related problems (DRPs) are prevalent among chronic kidney disease (CKD) patients. However, little is known about their severity and management by community pharmacists.
OBJECTIVES: To (a) describe the prevalence of DRPs by severity level in CKD patients and (b) assess the effect of a training-and-communication network program in nephrology (ProFiL) on these DRPs.
METHODS: This is a secondary analysis of a cluster randomized controlled trial evaluating the effect of the ProFiL-program. In 6 CKD clinics, patients at CKD stage 3 or 4 and their community pharmacists were recruited and assigned to the ProFiL group or a usual care (UC) group. Using validated criteria, 2 pharmacists identified DRPs and assessed their severity at baseline and after 12 months. The mean annual change in the number of DRPs per patient by severity level was assessed using a 2-level multivariable linear mixed-effects model.
RESULTS: A total of 494 pharmacists and 442 patients participated. At baseline, the prevalence (mean number of DRPs per patient [SD]) of mild DRPs (e.g., requiring dosage adjustment) and moderate DRPs (e.g., drug adherence requiring a monitoring plan) were 0.55 (0.98) and 1.04 (1.51), respectively. After 12 months, an unadjusted incremental annual reduction of 0.34 moderate DRPs (95% CI = -0.66 to -0.01) was observed in the ProFiL group compared with the UC group. After adjustment, no between-group differences were observed.
CONCLUSIONS: Among patients followed in CKD clinics, most DRPs have a moderate severity requiring specific monitoring by pharmacists. The benefit of continuing education programs, such as ProFiL, to reduce moderate DRPs remains to be determined.
DISCLOSURES: This study was supported by the Canadian Institutes of Health Research (grant number: MOP-230207). Part of the study was also funded by Pfizer Canada, Leo Pharma, and Amgen. The authors declare that they have no relevant financial interests. Study concept and design were contributed by Quintana-Bárcena, Lord, and Lalonde. Quintana-Bárcena, Lord, and Lizotte were responsible for the data analysis, and Quintana-Bárcena and Berbiche performed the statistical analysis. The manuscript was written by Quintana-Bárcena and Lalonde and revised by Quintana-Bárcena and Lalonde, along with the other authors.

PMID: 29384023 [PubMed - indexed for MEDLINE]

Important Aspects of Pharmacist-led Medication Reviews in an Acute Medical Ward.

Basic Clin Pharmacol Toxicol. 2018 Feb;122(2):253-261

Authors: Bülow C, Faerch KU, Armandi H, Jensen BN, Sonne J, Christensen HR, Christensen MB

Abstract
In some hospitals, clinical pharmacists review the medication to find drug-related problems (DRPs) in acutely admitted patients. We aimed to identify the nature of identified DRPs and investigate factors of potential importance for the clinical implementation of pharmacist suggestions. In 100 randomly selected medication review (MR) notes, we retrospectively evaluated the clinical implementation and classified (1) timing and communication of the review; (2) DRPs and related suggestions for the physician; and (3) DRPs' potential clinical relevance to patients as 'beneficial', 'somewhat beneficial', 'no relevance' or 'other relevance'. Of 327 DRPs (0-13 DRPs per patient), 42% were implemented. The clinical implementation was higher if the MR note was made prior to (instead of after) the physician's admission, and even higher if the suggestions were communicated verbally (instead of only in writing) to the physicians (44% versus 79%, p < 0.05). The clinical relevance of the DRPs was either 'beneficial' (16%), 'somewhat beneficial' (43%), 'no relevance' (22%) or 'other relevance' (19%). The 'beneficial' DRPs had a higher clinical implementation (53%) than 'no relevance' (34%) (p < 0.05). The most frequently implemented suggestions were based on DRPs concerning 'indication for drug treatment not noticed', 'inappropriate drug form' and 'drug dose too low', with implementation rates of 83%, 67% and 63%, respectively. In our sample, the pharmacist's MR suggestions were only implemented by physicians in 42% of the cases, but review prior to physician contact and verbal communication of the suggestions, higher clinical relevance and specific types of DRPs were associated with a higher implementation rate.

PMID: 28871627 [PubMed - indexed for MEDLINE]

Drug survival and reasons for discontinuation of the first biological disease modifying antirheumatic drugs in Thai patients with rheumatoid arthritis: Analysis from the Thai Rheumatic Disease Prior Authorization registry.

Int J Rheum Dis. 2018 Jan;21(1):170-178

Authors: Narongroeknawin P, Chevaisrakul P, Kasitanon N, Kitumnuaypong T, Mahakkanukrauh A, Siripaitoon B, Katchamart W, Thai Rheumatism Association

Abstract
AIM: To evaluate and compare the retention rate of biological disease-modifying antirheumatic drugs (bDMARDs) in real-life practice and identify risk factors related to remission and drug discontinuation in patients with rheumatoid arthritis (RA).
METHOD: A total of 256 patients fulfilling criteria for RA and starting bDMARD between December 2009 and October 2014 were selected from the Rheumatic Disease Prior Authorization registry. Baseline demographic and clinical data were recorded. The cumulative probability of bDMARD discontinuation over 5 years of follow-up and factors associated with RA remission and bDMARD withdrawal were analyzed.
RESULTS: Almost half (46%) of patients were initially treated with rituximab (RTX), with 33% treated with etanercept (ETN) and 21% with infliximab (IFX). Fewer than 10% were subsequently switched to a second bDMARD. The 1- and 5-year remission rates in patients continuing their first bDMARD were 7.2% and 21.5%, respectively. At 5 years, the drug survival rates for RTX, ETN and IFX were 50%, 25% and 22%, respectively. Multivariate analysis showed that RTX was significantly associated with highest drug survival. Relative to RTX, the hazard ratios for discontinuation of IFX and ETN were 2.60 (95% confidence interval [CI] 1.53-4.42) and 2.15 (95% CI 1.36-3.42), respectively. Thirty-nine percent of patients stopped treatments, due to inadequate response (42%), serious adverse events (22%), nonadherence (14%) or remission/low disease activity (13%).
CONCLUSION: Over 5 years, only one-third of patients continued using their first bDMARD. The leading cause of drug discontinuation was inadequate response.

PMID: 28737837 [PubMed - indexed for MEDLINE]

Safety and General Considerations for the Use of Antibodies in Infectious Diseases.

Adv Exp Med Biol. 2017;1053:265-294

Authors: Hey AS

Abstract
Monocolonal antibodies are valuable potential new tools for meeting unmet needs in treating infectious dieseases and to provide alternatives and supplements to antibiotics in these times of growing resistance. Especially when considering the ability to screen for antibodies reacting to very diverse target antigens and the ability to design and engineer them to work specifically to hit and overcome their strategies, like toxins and their hiding in specific cells to evade the immuneresponse and their special features enabling killing of the infectious agents and or the cells harbouring them. Antibodies are generally very safe and adverse effects of treatments with therapeutic antibodies are usually related to exaggeration of the intended pharmacology. In this chapter general safety considerations for the use of antibodies is reviewed and the general procedures for nonclinical testing to support their clinical development. Special considerations for anti-infective mAb treatments are provided including the special features that makes nonclinical safety programs for anti-infective mAbs much more simple and restricted. However at a cost since only limited information for clinical safety and modeling can be derived from such programs. Then strategies for optimally designing antibodies are discussed including the use of combination of antibodies. Finally ways to facilitate development of more than the currently only three approved mAb based treatments are discussed with a special focus on high costs and high price and how collaboration and new strategies for development in emerging markets can be a driver for this.

PMID: 29549644 [PubMed - indexed for MEDLINE]

The First Step to Integrating Adapted Common Terminology Criteria for Adverse Events for Children.

J Clin Oncol. 2016 06 20;34(18):2196-7

Authors: de Rojas T, Bautista FJ, Madero L, Moreno L

PMID: 27114600 [PubMed - indexed for MEDLINE]

The safety and tolerability of aripiprazole once-monthly as maintenance treatment for bipolar I disorder: A double-blind, placebo-controlled, randomized withdrawal study.

J Affect Disord. 2018 Jul 06;241:425-432

Authors: Calabrese JR, Sanchez R, Jin N, Amatniek J, Cox K, Johnson B, Perry PP, Hertel P, Such P, McQuade RD, Nyilas M, Carson WH

Abstract
BACKGROUND: Aripiprazole once-monthly 400 mg (AOM 400), an atypical long-acting injectable antipsychotic, has demonstrated efficacy and safety in maintenance treatment of bipolar I disorder (BP-I). We further assess safety and tolerability and characterize adverse events (AEs) across the duration of aripiprazole exposure.
METHODS: Patients with BP-I were stabilized on oral aripiprazole (2-8 weeks), AOM 400 (12-28 weeks), followed by 1:1 randomization of patients meeting stability criteria to a 52-week, double-blind, placebo-controlled withdrawal phase. Treatment-emergent AEs (TEAEs) were collected across study phases. AEs were counted in a phase if they were drug-related and continued from the baseline of that phase. A separate analysis on new-onset akathisia was conducted.
RESULTS: Among TEAEs occurring in ≥10% of patients during all study phases were akathisia (23.3%) and weight increased (10.6%). Median time to akathisia onset was 20 days after starting oral aripiprazole; median duration was 29 days for the first occurrence; 21/168 patients (12.5%) reporting akathisia experienced >1 episode. Episodes of new-onset akathisia decreased over time, with few events reported in the randomized phase. Weight gain was minimal with oral aripiprazole, generally starting within 3 months after the first AOM 400 injection, and appearing to plateau at 36 weeks. The mean weight gain within any study phase was ≤1.0 kg. Potentially clinically significant changes in metabolic parameters were uncommon.
LIMITATIONS: Patients on placebo had AOM 400 exposure before randomization.
CONCLUSION: These findings suggest that AEs with AOM 400 treatment were time-limited and support AOM 400 as a well-tolerated maintenance treatment of BP-I.

PMID: 30145513 [PubMed - as supplied by publisher]

Toward safer prescribing: evaluation of a prospective drug utilization review system on inappropriate prescriptions, prescribing patterns, and adverse drug events and related health expenditure in South Korea.

Public Health. 2018 Aug 23;163:128-136

Authors: Kim SJ, Han KT, Kang HG, Park EC

Abstract
OBJECTIVES: This study aimed to evaluate the effect of the prospective drug utilization review (DUR) system introduced in Korea in December 2010 as a real-time method to improve patient safety, in terms of changes in prescribing practices, adverse drug events (ADEs), and ADE-related healthcare expenditure, using non-steroidal anti-inflammatory drugs (NSAIDs) and their common ADEs as a guide.
STUDY DESIGN: We used an interrupted time-series study design using generalized estimating equations to evaluate changes in prescription rate and ADE-related healthcare expenditure. Cox regression analysis was used to evaluate the probability of NSAID-associated ADEs.
METHODS: A total of 154,585 outpatients with musculoskeletal or connective tissue disorders, without pre-existing gastric bleeding or ulcers were included in this study. The primary outcome was the level and trend change in prescription rate, drug-drug interactions, coprescribed gastro-protective drugs, and defined daily dose (DDD) of NSAIDs. The secondary outcome was the probability of ADEs and changes in ADE-related healthcare expenditure.
RESULTS: There was a significant trend change after introducing the DUR system in terms of drug-drug interactions (-3.6%) and coprescribed gastro-protective drugs (+0.6%). The mean DDD of NSAIDs increased by 0.2. The probability of ADEs decreased overall (-1.7%) and in the high-risk group (age ≥65 years; -9.6%); however, only the latter was significant. There was no significant trend or level change in ADE-related health expenditure.
CONCLUSIONS: The introduction of the DUR system was associated with more efficient prescribing, including a reduction in drug-drug interactions and an increase in the use of gastro-protective drugs. The system had a positive effect on patient outcome but was not associated with reduced ADE-related costs. Further studies are needed to evaluate the long-term effects of the DUR system in Korea.

PMID: 30145461 [PubMed - as supplied by publisher]

Suspected drug-induced liver injury associated with iguratimod: a case report and review of the literature.

BMC Gastroenterol. 2018 Aug 24;18(1):130

Authors: Li XL, Liu XC, Song YL, Hong RT, Shi H

Abstract
BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy.
CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment.
CONCLUSIONS: Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

PMID: 30143001 [PubMed - in process]

Drug-induced liver injury: a safety review.

Expert Opin Drug Saf. 2018 Aug;17(8):795-804

Authors: García-Cortés M, Ortega-Alonso A, Lucena MI, Andrade RJ, Spanish Group for the Study of Drug-Induced Liver Disease (Grupo de Estudio para las Hepatopatías Asociadas a Medicamentos GEHAM).l

Abstract
INTRODUCTION: Idiosyncratic drug-induced liver injury (DILI) remains one of the most important causes of drug attrition both in the early phases of clinical drug development and in the postmarketing scenario. This is because, in spite of emerging data on genetic susceptibility variants associated to the risk of hepatotoxicity, the precise identification of the individual who will develop DILI when exposed to a given drug remains elusive. Areas covered: In this review, we have addressed recent progress made and initiatives taken in the field of DILI from a safety perspective through a comprehensive search of the literature. Expert opinion: Despite the substantial progress made over this century, new approaches using big data analysis to characterize the true incidence of DILI are needed and to categorize the drugs' hepatotoxic potential. Genetic studies have highlighted the role of the adaptive immune system yet the mechanisms leading adaptation versus progression remain to be elucidated. There is a compelling need for development and qualification of sensitive, specific, and affordable biomarkers in DILI to foster drug development, patient treatment stratification and, improvement of causality assessment methods. Gaining mechanistic insights in DILI is essential to uncover therapeutic targets and design prospective clinical trials with appropriate endpoints.

PMID: 30059261 [PubMed - indexed for MEDLINE]

A narrative review of problems with medicines use in people with dementia.

Expert Opin Drug Saf. 2018 Aug;17(8):825-836

Authors: Eshetie TC, Nguyen TA, Gillam MH, Kalisch Ellett LM

Abstract
INTRODUCTION: People with dementia may be particularly susceptible to medication-related problems for various reasons. They include progressive cognitive decline, high sensitivity to the effect of medications on cognition and memory, and increased likelihood of comorbidities. Areas covered: This paper aimed to review current literature on the frequency and the types of medication-related problems, and their contribution to hospital admission in people with dementia. Literature searches were conducted using key search terms of dementia and medication-related problems. Studies investigating any medication-related problems in people with dementia or cognitive impairment were included. Expert opinion: Previous research showed a high prevalence of medication-related problems in people with dementia. However, no single category of medication-related problems was reported consistently as the most frequent type across studies. The available studies also showed that medication-related hospitalization was common among people with dementia. These findings underline the need for effective medication management services to reduce the risk of these problems in people with dementia and cognitive impairment. Further work is required to characterize medication-related problems comprehensively in this vulnerable patient group across settings of care. Future research should take a holistic approach in the identification of medication-related problems.

PMID: 29993294 [PubMed - indexed for MEDLINE]

Evaluating Twitter as a complementary data source for pharmacovigilance.

Expert Opin Drug Saf. 2018 Aug;17(8):763-774

Authors: Lardon J, Bellet F, Aboukhamis R, Asfari H, Souvignet J, Jaulent MC, Beyens MN, Lillo-LeLouët A, Bousquet C

Abstract
BACKGROUND: Social media are currently considered as a potential complementary source of knowledge for drug safety surveillance. Our primary objective was to estimate the frequency of adverse drug reactions (ADRs) experienced by Twitter users. Our secondary objective was to determine whether tweets constitute a valuable and informative source of data for pharmacovigilance purposes, despite limitations on character number per tweet.
RESEARCH DESIGN AND METHODS: We selected a list of 33 drugs subject to careful monitoring due to safety concern in France and Europe, and extracted tweets using the streaming API from 30 September 2014 to 5 April 2015. Two pharmacovigilance centers classified these tweets manually as potential ADR case reports.
RESULTS: Among 10,534 tweets, 848 (8.05%) implied or mentioned an ADR without meeting the four FDA criteria required for reporting an ADR, and 289 (2.74%) tweets were classified as 'case reports.' Among them 20 (7.27%) tweets mentioned an unexpected ADR and 33 (11.42%) tweets mentioned a serious ADR.
CONCLUSIONS: With the use of dedicated tools, Twitter could become a complementary source of information for pharmacovigilance, despite a major limitation regarding causality assessment of ADRs in individual tweets, which may improve with the new limitation to 280 characters per tweet.

PMID: 29991282 [PubMed - indexed for MEDLINE]