Angiotensin II receptor blockers (ARBs) and manufacturing contamination: A retrospective National Register Study into suspected associated adverse drug reactions.

AIMS: The aim of this study was to determine if any suspected adverse drug reactions (ADRs) observed with the use of angiotensin II receptor blockers (ARBs) could be linked to either (a) their unique respective physicochemical and pharmacological profiles and (b) the recently disclosed suspected carcinogenic manufacturing contaminants found in certain sartan drug class batches. METHODS: The pharmacology profiles of ARBs were data-mined from the Chemical Database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL). Suspected ADR data (from 01/2016-10/2022, inclusive) and prescribing rates of ARBs over a 5-year prescribing window (from 09/2016 to 08/2021, inclusive) were obtained via analysis of the United Kingdom Medicines and Healthcare products Regulatory Authority (MHRA) Yellow Card drug analysis profile and Open prescribing databases, respectively. RESULTS: The overall suspected ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied were found to be different between the sartan drug class members (chi-squared test, P < .05). There is a greater relative rate of reports for valsartan across all investigated organ classes of ADRs, than other ARBs, despite valsartan's more limited pharmacological profile and similar physicochemical properties to other sartans. The disparity in ADR reporting rates with valsartan vs other ARBs could be due to the dissimilarity in formulation excipients, patient factors and publicity surrounding batch contaminations, amongst others. Cancer-related ADRs and fatalities per 100 000 prescriptions identified across the ARBs studied are not statistically significant (chi-squared test, P > .05) based on the datasets used over the 5-year period. CONCLUSION: No connection between ARB pharmacology and their suspected ADRs could be found. No conclusion between sartan batch contaminations and increased suspected cancer-related ADRs was found.

Antibiotic oral provocation challenge in children.

AIM: The main objective of this study was to see how many of the children, with a suspected antibiotic allergy, developed an allergic or adverse reaction to a drug provocation test. METHODS: Data on children that had undergone a drug provocation test for a suspected antibiotic allergy were compiled retrospectively for the period from 2007-2018. The median age at the first provocation was 2.25 years (1.5-5.7). Standardised questionnaires, the children's parents had answered before the provocation, were used to evaluate the originally suspected allergic reaction, previous health, atopic diseases and family history. RESULTS: Ninety-two (6.4%) of the 1440 children showed a possible mild allergic reaction. Sixty-four of the 92 children underwent a second drug provocation test 1-2 years later. At that time, only eleven developed a positive- or a possible-delayed reaction. CONCLUSION: An immediate moderate or severe allergic reaction was excluded in all cases of suspected antibiotic allergy in this study. Our study indicates that an oral drug provocation test is safe. It may be appropriate to wait for 6 months or more after the initial event of ADR before these tests are performed. A second oral provocation 1-2 years after the first one shows that ADRs are outgrown in most children.

The effect of clinical pharmacists' intervention in adverse drug reaction reporting: a retrospective analysis with a 9-year interrupted time series.

BACKGROUND: In China, 85.4% of adverse drug reactions (ADRs) are spontaneously reported by healthcare facilities. As a result, many ADRs are not reported due to lack of mandatory reporting requirements. As healthcare professionals, clinical pharmacists (CPhs) serve as a bridge between clinical work and medication and ensure rational drug use. In China, A team of CPhs implemented an intervention for ADRs reporting, with the goal of improving the number of ADRs reports, the number of unreported ADRs, and the standardized reporting rate. METHODS: On June 01, 2015, a team of CPhs implemented an intervention for ADRs reporting at a Grade A, Class 3 hospital in China. The drug review catalogue (DRC) was used to screen physician orders for having visible symptoms of ADRs across departments, pooled the ADRs, and submitted them to the Center for Advanced Drug Monitoring (CNCAM). We retrospectively analysed the effect of a CPhs ADRs reporting intervention on the number of clinical ADRs reports, the number of unreported ADRs, and the standardized reporting rate over a 9-year period by interrupted time series (ITS). The method was implemented at the hospital on June 1, 2015, and a segmented regression model was used to analyse the data from January 1, 2010, to December 31, 2019. RESULTS: After the CPhs ADRs reporting intervention, the number of inpatient ADRs reports submitted to the CNCAM immediately increased by approximately 63 (62.658, P < 0.01) and then decreased by approximately 1 (0.701, P = 0.000151 < 0.01) per month afterward; the number of unreported ADRs was immediately reduced by approximately 44 (44.091, P < 0.01) and remained largely unchanged over time (P > 0.05); the standardized ADRs reporting rate per month immediately increased by 63.634% (P < 0.01) and remained largely unchanged over time (P > 0.05). CONCLUSION: The CPhs ADRs reporting intervention had an immediate effect on improving ADRs reporting, which highlights the severity of ADRs underreporting in Chinese hospitals. The method is practical and should be used more widely in clinical practice. For example, the method can adjust and establish a DRC catalog that meets the actual situation of the implementing hospital based on the hospital's drug use habits and has the characteristics of good adaptability. However, it does have some limitations; for example, it may be difficult to detect early ADRs without visible symptoms.

Smartphone-based mobile applications for adverse drug reactions reporting: global status and country experience.

BACKGROUND: Smartphone technology can support paperless reporting of adverse drug reactions (ADRs). The aims of this study were to systematically assess smartphone ADR-reporting applications, understand their qualitative and quantitative impact on ADR reporting, and garner key lessons from owners and developers. METHODS: This study had three components: (1) An assessment of ADR-reporting apps, (2) an online survey on the impact of app implementation on ADR reporting and the experiences of app developers and owners, and (3) a search of VigiBase, the World Health Organization global database of individual case safety reports (ICSRs), to observe trends in the number of ADR reports targeting countries where the apps were implemented. RESULTS: Twenty-two apps were included. Eight out of the 22 apps were for countries in the WHO African region. Features observed included E2B data elements (E stands for efficacy) and functions supporting reporting and user engagement. Seventeen app developers and owners answered to the survey and reported overall positive experiences with app features, and post-launch increases in the total number of ICSRs. User type and user environment were cited as factors influencing app use: Respondents said younger people and/or those with an inclination to use technology were more likely to use apps compared to older or more technology-averse people, while respondents in countries with limited internet connectivity reported persistent difficulties in app use. CONCLUSIONS: Smartphone apps for reporting ADRs offer added value compared to conventional reporting tools. Reporting tools should be selected based on interface features and factors that may influence app usage.

A Novel and Adaptive Angle Diversity-Based Receiver for 6G Underground Mining VLC Systems.

Visible light communication (VLC) is considered an enabling technology for future 6G wireless systems. Among the many applications in which VLC systems are used, one of them is harsh environments such as Underground Mining (UM) tunnels. However, these environments are subject to degrading environmental and intrinsic challenges for optical links. Therefore, current research should focus on solutions to mitigate these problems and improve the performance of Underground Mining Visible Light Communication (UM-VLC) systems. In this context, this article presents a novel solution that involves an improvement to the Angle Diversity Receivers (ADRs) based on the adaptive orientation of the Photo-Diodes (PDs) in terms of the Received Signal Strength Ratio (RSSR) scheme. Specifically, this methodology is implemented in a hemidodecahedral ADR and evaluated in a simulated UM-VLC scenario. The performance of the proposed design is evaluated using metrics such as received power, user data rate, and bit error rate (BER). Furthermore, our approach is compared with state-of-the-art ADRs implemented with fixed PDs and with the Time of Arrival (ToA) reception method. An improvement of at least 60% in terms of the analyzed metrics compared to state-of-the-art solutions is obtained. Therefore, the numerical results demonstrate that the hemidodecahedral ADR, with adaptive orientation PDs, enhances the received optical signal. Furthermore, the proposed scheme improves the performance of the UM-VLC system due to its optimum adaptive angular positioning, which is completed according to the strongest optical received signal power. By improving the performance of the UM-VLC system, this novel method contributes to further consideration of VLC systems as potential and enabling technologies for future 6G deployments.

Immune checkpoint inhibitors and potential risk of thromboembolic events: Analysis of the WHO global database of individual case safety reports.

Introduction: Thromboembolic events with the use of immune checkpoint inhibitors (ICIs) in patients with cancer have been reported in few studies. However, the detailed profile of these cases remains mostly uncertain. Method: A descriptive analysis of Thromboembolic events associated with ICIs retrieved from the VigiBase, between 1967 to November 2020. We extracted the data using the terms of 'pulmonary embolism' OR 'deep vein thrombosis' OR 'acute coronary syndrome' OR 'myocardial infarction' OR 'ischemic stroke' (preferred term (PT) (MedDRA). Results: We included 161 cases from 26 countries in our descriptive analysis. Patients' ages were reported in 141 (87.6%) cases, with a median of 68 years (interquartile range 61-74), and 63.4% of the patients were male. Indications for ICIs were reported in 151 (93.8%) cases, as follows: lung cancer (n = 85, 52.8%), renal cell carcinoma (n = 24, 14.9%), melanoma (n = 20, 12.4%), urethral carcinoma (n = 12, 7.45%), breast cancer (n = 4, 2.48%), adenocarcinoma of the gastroesophageal junction (n = 3, 1.9%), gastric cancer (n = 2, 1.24%), and skin cancer (n = 1, 0.62%). Nivolumab was reported as a suspected drug in 76 cases (47%), pembrolizumab in 46 cases (28.5%), atezolizumab in 21 cases (13%), durvalumab in 14 cases (8.6%), and avelumab in four cases (2.4%).The time to onset of thromboembolic events was reported in 127 (78.8%) cases. Most of these patients (n = 109, 85.8%) reported thromboembolic events within the first six months. The causality assessment of included cases showed that 50.3% of reported thromboembolic events were possibly related to the suspected reported medication, 13.7% were probably related, 13% were unlikely to be related, and 23% were not assessable due to insufficient information. Conclusion: This study demonstrates a possible association between the use of ICIs and thromboembolic events. Further epidemiological studies are needed to assess this association and to elucidate the underlying mechanism.

Prevalence of exposure to pharmacogenetic drugs by the Saudis treated at the health care centers of the Ministry of National Guard.

Background: The drugs impacted by genetic variants are known as pharmacogenetic (PGx) drugs. Patients' responses to these drugs may vary according to the variability in patients' genetic makeup. Hence, exploring the pharmacogenes that affect drug treatment is vital to ensure optimal therapy and patients' safety. This study aimed to describe the usage rate of PGx drugs and the frequency of relevant variants in the Saudi population. Methodology: Prescription patterns over seven years (2015-2021) for Saudi patients on PGx drugs treated at the Ministry of National Guard-Health Affairs (MNG-HA) were investigated. Only registered drugs in the MNG-HA formulary (n = 78) were included. The patients were subgrouped into four age groups: ≤24, 25-44, 45-64, and ≥65 years. Further subgrouping was made according to gender and drugs' therapeutic categories following anatomical therapeutic chemical (ATC) classification.Furthermore, an online searching was carried out to identify the pharmacogenes reported in the literature among healthy Saudis. The search included 45 genes that may affect drug outcomes based on evidence rated by either CPIC (A-B levels) or PharmGKB (1-2 levels). Results: The screened patients were 1,483,905. Patients on PGx drugs accounted for 46.7% (n = 693,077 patients). The analgesic group was the most prescribed drug category (47%), which included ibuprofen (20.5%), celecoxib (6.3%), tramadol (5.8%), and others. Cardiovascular agents were the second-most utilized drug class (24.4%). Omeprazole was the second most commonly used medication (11.1%) but ranked third as a class (gastroenterology). Females used PGx drugs more frequently than males (53.5% versus 46.5%) and a higher usage rate by patients aged 45-64 years (31.3%) was noted. The cytochrome P450 genes (CYP2C9, CYP2C19, and CYP2D6) were estimated to impact responses of 54.3% (n = 1,156,113) of the used drugs (27.2% are possibly affected by CYP2C9, 12.8% by CYP2C19, and 14.3% by CYP2D6). Thirty-five pharmacogenes that characterize Saudi population and their variants' allele frequencies were identified from previous reports. This study presents the largest reported number of genes that may affect drug therapies among Saudis. Conclusion: This study confirmed that a high percentage of Saudi patients use PGx drugs and various genotypes of certain pharmacogenes are inherited by the Saudi population.

Medical students as junior adverse drug event managers facilitating reporting of ADRs.

The Junior Adverse Drug Event Manager (J-ADEM) team is a multifaceted intervention focusing on real-life education for medical students that has been shown to assist healthcare professionals in managing and reporting suspected adverse drug reactions (ADRs) to the Netherlands Pharmacovigilance Centre Lareb. The aim of this study was to quantify and describe the ADRs reported by the J-ADEM team and to determine the clinical potential of this approach. The J-ADEM team consisted of medical students tasked with managing and reporting ADRs in hospitalized patients. All ADRs screened and reported by J-ADEM team were recorded anonymously, and categorized and analysed descriptively. From August 2018 through January 2020, 209 patients on two wards in an academic hospital were screened for ADR events. The J-ADEM team reported 101 ADRs. Although most ADRs (67%) were first identified by healthcare professionals and then reported by the J-ADEM team, the team also reported an additional 33 not previously identified serious ADRs. In 10% of all reported ADRs, the J-ADEM team helped optimize ADR treatment. The ADR reports were largely well-documented (78%), and ADRs were classified as type A (66%), had a moderate or severe severity (85%) and were predominantly avoidable reactions (69%). This study shows that medical students are able to screen patients for ADRs, can identify previously undetected ADRs and can help optimize ADR management. They significantly increased (by 300%) the number of ADR reports submitted, showing that the J-ADEM team can make a valuable clinical contribution to hospital care.

An OMOP-CDM based pharmacovigilance data-processing pipeline (PDP) providing active surveillance for ADR signal detection from real-world data sources.

BACKGROUND: Adverse drug reactions (ADRs) are regarded as a major cause of death and a major contributor to public health costs. For the active surveillance of drug safety, the use of real-world data and real-world evidence as part of the overall pharmacovigilance process is important. In this regard, many studies apply the data-driven approaches to support pharmacovigilance. We developed a pharmacovigilance data-processing pipeline (PDP) that utilized electronic health records (EHR) and spontaneous reporting system (SRS) data to explore pharmacovigilance signals. METHODS: To this end, we integrated two medical data sources: Konyang University Hospital (KYUH) EHR and the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). As part of the presented PDP, we converted EHR data on the Observation Medical Outcomes Partnership (OMOP) data model. To evaluate the ability of using the proposed PDP for pharmacovigilance purposes, we performed a statistical validation using drugs that induce ear disorders. RESULTS: To validate the presented PDP, we extracted six drugs from the EHR that were significantly involved in ADRs causing ear disorders: nortriptyline, (hazard ratio [HR] 8.06, 95% CI 2.41-26.91); metoclopramide (HR 3.35, 95% CI 3.01-3.74); doxycycline (HR 1.73, 95% CI 1.14-2.62); digoxin (HR 1.60, 95% CI 1.08-2.38); acetaminophen (HR 1.59, 95% CI 1.47-1.72); and sucralfate (HR 1.21, 95% CI 1.06-1.38). In FAERS, the strongest associations were found for nortriptyline (reporting odds ratio [ROR] 1.94, 95% CI 1.73-2.16), sucralfate (ROR 1.22, 95% CI 1.01-1.45), doxycycline (ROR 1.30, 95% CI 1.20-1.40), and hydroxyzine (ROR 1.17, 95% CI 1.06-1.29). We confirmed the results in a meta-analysis using random and fixed models for doxycycline, hydroxyzine, metoclopramide, nortriptyline, and sucralfate. CONCLUSIONS: The proposed PDP could support active surveillance and the strengthening of potential ADR signals via real-world data sources. In addition, the PDP was able to generate real-world evidence for drug safety.

Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions.

Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death and illness in developed countries. ADRs show differential features depending upon genotype, age, sex, race, pathology, drug category, route of administration, and drug-drug interactions. Pharmacogenomics (PGx) provides the physician effective clues for optimizing drug efficacy and safety in major problems of health such as cardiovascular disease and associated disorders, cancer and brain disorders. Important aspects to be considered are also the impact of immunopharmacogenomics in cutaneous ADRs as well as the influence of genomic factors associated with COVID-19 and vaccination strategies. Major limitations for the routine use of PGx procedures for ADRs prevention are the lack of education and training in physicians and pharmacists, poor characterization of drug-related PGx, unspecific biomarkers of drug efficacy and toxicity, cost-effectiveness, administrative problems in health organizations, and insufficient regulation for the generalized use of PGx in the clinical setting. The implementation of PGx requires: (i) education of physicians and all other parties involved in the use and benefits of PGx; (ii) prospective studies to demonstrate the benefits of PGx genotyping; (iii) standardization of PGx procedures and development of clinical guidelines; (iv) NGS and microarrays to cover genes with high PGx potential; and (v) new regulations for PGx-related drug development and PGx drug labelling.

Evaluating the frequency, consumers' motivation and perception of online medicinal, herbal, and health products purchase safety in Saudi Arabia.

OBJECTIVES: Purchasing medicinal products from the internet has become more popular in the last three decades. Understanding consumers' use and perception of the safety of medicinal products obtained online is essential. Therefore, this study aims to evaluate the extent of medicines purchased from the internet in Saudi Arabia, types of products, sources of information, the satisfaction, the motivational factors, and estimate consumers' vigilance and tendency to report ADRs if occurred. DESIGN: A prospective cross-sectional study using a custom-designed questionnaire was conducted among community adults in Saudi Arabia, age ≥ 18. SETTING: Evaluation of community subjects' perception towards buying medicinal products was done through the internet in Saudi Arabia from 1st July 2020 until the end of August 2020. MAIN OUTCOME MEASURES: The main outcome of the study was purchasing medicinal products from the internet (Yes, No). RESULTS: Overall, 36% of the study participants (n = 643) have ever bought medicinal products from the internet (Table 2). Of those, the most obtained was herbal medicine, supplements, or cosmetics (61.3%). Motivational factors towards purchasing medicinal products from the internet were mostly positive, with the most commonly reported agreed motivational factors were lower cost (55.7%), easy online access (54.1%), a wide variety of products (52.6%), and more privacy (43.6%). Around 60.4% of participants believed that buying medicinal products from the internet can be safe. The most perceived risk was the difficulty of distinguishing between registered online pharmacies and other unlicensed commercial websites, with only 32.7% of the participants distinguishing between registered and unlicensed commercial websites. CONCLUSIONS: This study sheds light on the consumers' use and perception of the safety and risks of medicinal products purchased from the internet. The study findings noticeably describe the great need to increase safety awareness about obtaining medicinal products from the internet among the Saudi community.

Knowledge, Attitude, and Barriers Toward ADRs Reporting Among Health-Care Professionals at Tertiary Care Health Settings in Peshawar, Pakistan: A Web Based Study.

Background: Underreporting of adverse drug reactions (ADRs) is considered a major determinant of poor ADR signal detection in Pakistan. Considering this, the study was proposed to evaluate healthcare professionals' (HCPs) knowledge attitude toward and the barriers that discourse ADRs reporting. Methods: A cross-sectional survey was distributed among HCPs in 3 major tertiary care facilities of Peshawar. A self-administered, 31 items questionnaire was circulated online to collect the required information. Relative index ranking was used to identify the top barriers to the ADR reporting process. Results: HCPs (n = 322) were requested, and over one-third (n = 122) responded. Of the total, 97 (79.5%) were males, and by designation, 59(48.4%) were resident medical officers. About 45% of the HCPs did not identify the appropriate pharmacovigilance (PV) definition. More than half of the HCPs (52.2%) distinguished the appropriate PV purpose. Nearly 80% HCPs did not know the acceptable reporting time frame, while 22.1% HCPs knew that regulatory body for ADRs does not exist in Pakistan. The majority (95.08%) of the HCPs either strongly agreed or agreed that reporting an ADRs is a professional obligation and all the HCPs were of the opinion that PV should be taught in detail to HCPs. Exploring the barriers, it was identified that the key barriers to ADRs reporting were "unavailability of professional environment to discuss ADRs," Relative Importance Index (RII) = 0.813, "lack of incentives for reporting" (RII = 0.774), "lack of knowledge regarding reporting" (RII = 0.693), and "insufficient knowledge of pharmacotherapy in detecting ADRs" (RII = 0.662). In addition to these, "complicated reporting forms" (RII = 0.616), "lack of motivation for reporting ADRs" (RII = 0.610), and "absence of professional confidence" were seen as major hindrances in effective reporting of ADRs (RII = 0.598). Conclusion: Concerning PV and ADR reporting poor knowledge was noted. However, the majority of the HCPs showed an explicit attitude regarding ADRs reporting. The majority of the HCPs disclosed unavailability of professional environment to discuss about ADRs, lack of incentives, and how to report the main factors hindering the ADRs reporting. It is emphasized that health authorities carve out a niche for a well purposeful PV center and pledge educational activities and trainings for increasing understanding and approaches regarding reporting of ADR.

Drug Development and the Use of Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Disease Modeling and Drug Toxicity Screening.

: Over the years, numerous groups have employed human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as a superb human-compatible model for investigating the function and dysfunction of cardiomyocytes, drug screening and toxicity, disease modeling and for the development of novel drugs for heart diseases. In this review, we discuss the broad use of iPSC-CMs for drug development and disease modeling, in two related themes. In the first theme-drug development, adverse drug reactions, mechanisms of cardiotoxicity and the need for efficient drug screening protocols-we discuss the critical need to screen old and new drugs, the process of drug development, marketing and Adverse Drug reactions (ADRs), drug-induced cardiotoxicity, safety screening during drug development, drug development and patient-specific effect and different mechanisms of ADRs. In the second theme-using iPSC-CMs for disease modeling and developing novel drugs for heart diseases-we discuss the rationale for using iPSC-CMs and modeling acquired and inherited heart diseases with iPSC-CMs.

Predicting adverse drug reactions of combined medication from heterogeneous pharmacologic databases.

BACKGROUND: Early and accurate identification of potential adverse drug reactions (ADRs) for combined medication is vital for public health. Existing methods either rely on expensive wet-lab experiments or detecting existing associations from related records. Thus, they inevitably suffer under-reporting, delays in reporting, and inability to detect ADRs for new and rare drugs. The current application of machine learning methods is severely impeded by the lack of proper drug representation and credible negative samples. Therefore, a method to represent drugs properly and to select credible negative samples becomes vital in applying machine learning methods to this problem. RESULTS: In this work, we propose a machine learning method to predict ADRs of combined medication from pharmacologic databases by building up highly-credible negative samples (HCNS-ADR). Specifically, we fuse heterogeneous information from different databases and represent each drug as a multi-dimensional vector according to its chemical substructures, target proteins, substituents, and related pathways first. Then, a drug-pair vector is obtained by appending the vector of one drug to the other. Next, we construct a drug-disease-gene network and devise a scoring method to measure the interaction probability of every drug pair via network analysis. Drug pairs with lower interaction probability are preferentially selected as negative samples. Following that, the validated positive samples and the selected credible negative samples are projected into a lower-dimensional space using the principal component analysis. Finally, a classifier is built for each ADR using its positive and negative samples with reduced dimensions. The performance of the proposed method is evaluated on simulative prediction for 1276 ADRs and 1048 drugs, comparing using four machine learning algorithms and with two baseline approaches. Extensive experiments show that the proposed way to represent drugs characterizes drugs accurately. With highly-credible negative samples selected by HCNS-ADR, the four machine learning algorithms achieve significant performance improvements. HCNS-ADR is also shown to be able to predict both known and novel drug-drug-ADR associations, outperforming two other baseline approaches significantly. CONCLUSIONS: The results demonstrate that integration of different drug properties to represent drugs are valuable for ADR prediction of combined medication and the selection of highly-credible negative samples can significantly improve the prediction performance.

Predicting toxicities of reactive metabolite-positive drug candidates.

Because of the inability to predict and quantify the risk of idiosyncratic adverse drug reactions (IADRs) and because reactive metabolites (RMs) are thought to be responsible for the pathogenesis of some IADRs, the potential for RM formation within new chemical entities is routinely examined with the ultimate goal of eliminating or reducing the liability through iterative design. Likewise, avoidance of structural alerts is almost a standard practice in drug design. However, the perceived safety concerns associated with the use of structural alerts and/or RM screening tools as standalone predictors of toxicity risks may be overexaggerated. Numerous marketed drugs form RMs but do not cause idiosyncratic toxicity. In this review article, we present a critique of the structural alert/RM concept as applied in drug discovery and evaluate the evidence linking structural alerts and RMs to observed toxic effects. Pragmatic risk mitigation strategies to aid the advancement of drug candidates that carry a RM liability are also discussed.

Clinically relevant drug-drug interactions among elderly people with dementia.

PURPOSE: Increased numbers of drugs and changes in pharmacokinetic and pharmacodynamic parameters among elderly people contribute to increased prevalence of adverse drug reactions. Drug-drug interactions (DDIs) are an important reason for admission to hospital and elderly people with dementia are particularly vulnerable. The aims of the present study were to assess the occurrence and characteristics of clinically relevant DDIs and to investigate potential risk factors associated with DDIs among elderly people with dementia. METHODS: People ≥ 65 years with dementia, admitted to two hospitals in Northern Sweden, were included. The medical records of 458 patients were reviewed. Clinically relevant DDIs were identified using the Janusmed interactions database. Pharmacological classification was conducted using Stockley's classification system. RESULTS: A total of 401 DDIs were identified among 43.2% of the study population, of which 98.5% had interactions that may require dose adjustment and 7.6% had drug combinations that should be avoided. Pharmacodynamic interactions were most common, of which furosemide-citalopram (n = 35) were most frequently observed. Omeprazol-citalopram (n = 25) was the most common drug combination among pharmacokinetic interactions. Citalopram and warfarin were the most commonly involved drug substances. An association was found between a higher number of medications being prescribed and having at least one DDI. CONCLUSION: Clinically relevant drug-drug interactions are prevalent among elderly people with dementia living in Northern Sweden. Drug-drug interactions should be identified in order to manage and prevent adverse outcomes. This is particularly important among this group of people especially when multiple medications are being prescribed.

Post-marketing safety surveillance and re-evaluation of Xueshuantong injection.

BACKGROUND: Traditional Chinese medicine injections (TCMIs) have been widely used to treat severe and acute diseases due to their high bioavailability, accurate curative effect, and rapid effect. However, incidence rates of adverse drug reactions (ADRs) of TCMIs have also increased in recent years. Xueshuantong injection (XSTI) is a commonly-used TCMI comprised of Panax notoginseng total sapiens for the treatment of stroke hemiplegia, chest pain, and central retinal vein occlusion. Its safety remains uncelar. Therefore, post-marketing safety of XSTI was studied in this research. METHODS: In present study, post-marketing safety surveillance and re-evaluation of XSTI were reported. Thirty thousand eight hundred eighty-four patients in 33 hospitals from 7 provinces participated in this study. Incidence rate, most common clinical manifestations, types, severity, occurrence time, and disposal of ADRs were calculated. RESULTS: Incidence rate of ADR of XSTI was 4.14‰ and the most common clinical manifestations were skin and its appendages damage. Type A accounts for 95.49% of ADRs of XSTI and most of them (41.41%) were occurred within 24 h after receiving XSTI treatment. Severities of most ADRs of XSTI were moderate reactions (86.72%). Main disposition of ADRs of XSTI was drug withdrawal and symptomatic treatment (54.69%). CONCLUSIONS: Our data provide basis for improvement of instructions of XSTI and clinical safety of XSTI. Post-marketing surveillance of TCMIs in this study is a powerful tool to identify types and manifestations of ADRs to improve safety and effectiveness of drugs in clinical applications. TRIAL REGISTRATION: This protocol has international registration in China clinical trial registration center ( ChiCTR~OPC~ 14,005,718 ) at December 22, 2014.

Public awareness of adverse drug reaction medical safety.

Purpose The purpose of this paper is to contribute to the literature by assessing factors that typically engender adverse drug reactions (ADRs) jeopardizing medical safety. These factors are population knowledge, clarity in disclosure of the risks inhering ADRs and ADRs incidence. It seeks to minimize negative effect by early identification of drug reactions. Design/methodology/approach On the one hand, the study employs a model that shows relationships between various factors, and on the other hand, ADRs medical safety in the public healthcare sector. Findings Clarity of consultancy services in public healthcare significantly impact ADR medical safety. Population and healthcare provider education on ADRs medical safety are necessities. Implementation of an ADR reporting system in every healthcare institute is essential. This helps service providers to give a clear and accurate information to patients. It also makes patients more aware of consequences of ADRs. Research limitations/implications Time, place and sampling method are found to be the main study limitations. Researchers should take into their consideration the significant relationships between the factors and ADRs medical safety to improve level of awareness in the healthcare public sector. Practical implications Ways to improve ADR medical safety in healthcare sector are underscored. Healthcare service providers and professionals need to take into account the stipulated study factors in order to improve medical safety and reduce unnecessary medical costs. Originality/value Very few studies have been conducted on this topic; most of those that have been conducted were undertaken in western countries. This study assesses the level of healthcare safety in the country and suggests mechanisms to elevate that level.

A survey on gastrointestinal adverse drug reactions of Doxorubicin and Cyclophosphamide combination therapy.

Adverse drug reactions (ADRs) are very common with anticancer drugs. The objectives of the survey are to evaluate ADRs of AC (Adriamycin (Doxorubicin) and Cyclophosphamide) combination therapy with special reference to GIT (Gastrointestinal system). It was a prospective, descriptive, observational study which included 90 female patients receiving AC combination therapy for their treatment through a purposive sampling and from 01-01-2016 to 31-12-2016 at Cancer Hospital Jamshoro Pakistan. Patients were interviewed during follow up session with a consultant, their response was recorded in a questionnaire and verified through British National formulary (BNF), Hartwig & Siegel scale (ADR severity assessment scale). The survey results shows that AC anticancer combination therapy can result in various disturbances in gastrointestinal tract among which nausea, vomiting decreased appetite and hyperacidity were most common. These must be taken into account and managed with supportive treatment in order to maintain better quality of life during the cancer treatment.

[Does methylphenidate cause liver damage? An analysis of ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)"]. / Induziert Methylphenidat Leberschäden? ­ Analyse von Spontanmeldungen an das Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM).

Does methylphenidate cause liver damage? An analysis of ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)" Abstract. Ad hoc reports to the "Bundesinstitut für Arzneimittel und Medizinprodukte" (BfArM, the German Federal Institute for Drugs and Medical Devices) were analyzed concerning liver injuring stemming from therapy with methylphenidate (MPH). Clinical criteria were used to assess suspected cases of causal association. The BfArM database on adverse drug reactions (ADRs) recorded suspected cases from Germany over the period from 1 January 2006 to 23 May 2016. Using the Standardized MedDRA Queries (SMQ) search strategy, we searched the database for "MPH" and its potential ADRs "Hepatic Disorder." The ad hoc reports were checked for completeness and assessed clinically according to the Uppsala Monitoring Centre criteria. 60 suspected cases of liver damages by MPH were recorded in the database. In 15 thereof, an assessment was not possible because of insufficient documentation; in 25 cases, a link between the intake of MPH and the occurrence of liver injury was considered "unlikely." A "possible" causality was assessed in 11 cases, a "probable/likely" causality in 9 cases: 1 patient with fulminant hepatitis, 1 with increased size of benign liver tumor, and 18 cases of (reversible) hepatic enzyme elevation. According to our evaluation, MPH is well-tolerated with regard to liver and gall bladder diseases. For patients with hepatic impairment or other risk factors, regular monitoring of liver values is recommended.