Optimal Glycaemic Control in Elderly People with Type 2 Diabetes: What Does the Evidence Say?
Abstract The global prevalence of type 2 diabetes mellitus (T2DM) is rising in an ageing population through a combination of lifestyle changes and greater longevity. However, by excluding participants aged over 70 years, most major interventional trials on which current diabetes therapeutic guidelines are based have failed to provide specific evidence to support the prescribed management of diabetes in elderly people. While diabetes per se has a significant impact on the elderly person, the side effects of medications, particularly hypoglycaemia, prevent optimisation of diabetes treatment. Hypoglycaemia is associa...
Source: Drug Safety - December 7, 2014 Category: Drugs & Pharmacology Source Type: research

Bacillus Calmette-Guérin (BCG) Vaccine Adverse Events in Victoria, Australia: Analysis of Reports to an Enhanced Passive Surveillance System
Conclusion Effective AEFI surveillance is of paramount importance as countries are faced with unplanned vaccine strain changes following the 2012 BCG recall and subsequent global vaccine supply shortages. The Australian experience and lessons learned serve as a timely reminder to BCG vaccination programmes worldwide to review AEFI surveillance systems. (Source: Drug Safety)
Source: Drug Safety - December 5, 2014 Category: Drugs & Pharmacology Source Type: research

Aristolochic Acid Nephropathy: Epidemiology, Clinical Presentation, and Treatment
Abstract Aristolochic acid (AA) is a compound extracted from the Aristolochia species of herbs. It has been used for centuries as a remedy for various illnesses and diseases. However, in the early 1990s in the setting of a weight loss herbal remedy, AA exposure was associated with a syndrome of kidney injury, termed aristolochic acid nephropathy (AAN). This entity is marked by elevated serum creatinine, significant anemia, and histopathologic changes demonstrating a hypocellular interstitial infiltrate with severe fibrosis. Progression towards end-stage renal disease (ESRD) is rapid, with most patients having chro...
Source: Drug Safety - December 2, 2014 Category: Drugs & Pharmacology Source Type: research

Comment on: “Zoo or Savannah? Choice of Training Ground for Evidence-Based Pharmacovigilance”
(Source: Drug Safety)
Source: Drug Safety - November 29, 2014 Category: Drugs & Pharmacology Source Type: research

Authors’ Reply to Harpaz et al. Comment on: “Zoo or Savannah? Choice of Training Ground for Evidence-Based Pharmacovigilance”
(Source: Drug Safety)
Source: Drug Safety - November 29, 2014 Category: Drugs & Pharmacology Source Type: research

The Comparative Efficacy and Safety of the Angiotensin Receptor Blockers in the Management of Hypertension and Other Cardiovascular Diseases
Abstract All national guidelines for the management of hypertension recommend angiotensin receptor blockers (ARBs) as an initial or add-on antihypertensive therapy. The eight available ARBs have variable clinical efficacy when used for control of hypertension. Additive blood pressure-lowering effects have been demonstrated when ARBs are combined with thiazide diuretics or dihydropyridine calcium channel blockers, augmenting hypertension control. Furthermore, therapeutic use of ARBs goes beyond their antihypertensive effects, with evidence-based benefits in heart failure and diabetic renal disease particularly amon...
Source: Drug Safety - November 22, 2014 Category: Drugs & Pharmacology Source Type: research

Comment on: “Adverse Drug Reaction Reporting by Patients: An Overview of Fifty Countries”
(Source: Drug Safety)
Source: Drug Safety - November 21, 2014 Category: Drugs & Pharmacology Source Type: research

Authors’ Reply to Ahmad SR: “Adverse Drug Reaction Reporting by Patients: An Overview of Fifty Countries”
(Source: Drug Safety)
Source: Drug Safety - November 21, 2014 Category: Drugs & Pharmacology Source Type: research

Acknowledgement to Referees
(Source: Drug Safety)
Source: Drug Safety - November 15, 2014 Category: Drugs & Pharmacology Source Type: research

A Description of Signals During the First 18 Months of the EMA Pharmacovigilance Risk Assessment Committee
Conclusions The importance of spontaneous reporting in signal detection and monitoring of safety issues throughout the entire life cycle of a medicinal product is confirmed in this study. The amount of time a drug has been on the market is correlated with the number of signals detected. The PRAC decision-making process seems efficient particularly with respect to serious concerns; its role in improving signal prioritization and real-time signal management will be further clarified in its subsequent years of operation. (Source: Drug Safety)
Source: Drug Safety - November 15, 2014 Category: Drugs & Pharmacology Source Type: research

Use of Logistic Regression to Combine Two Causality Criteria for Signal Detection in Vaccine Spontaneous Report Data
Conclusions Logistic regression allows estimation of the probability of a vaccine–event pair being an ARFI using two causality criteria at the population level assessed in spontaneous report data: the strength of association (disproportionality measure) and temporality (TTO distribution tests). Logistic regression combines and weights these causality criteria based on their respective ability to predict known safety issues. (Source: Drug Safety)
Source: Drug Safety - November 14, 2014 Category: Drugs & Pharmacology Source Type: research

Balancing Benefits and Risks in Patients Receiving Incretin-Based Therapies: Focus on Cardiovascular and Pancreatic Side Effects
Abstract Incretin-based therapies either increase endogenous levels of glucagon-like peptide-1 by prolonging its half-life (DPP-4 inhibitors) or directly stimulate its receptor (glucagon-like peptide-1 analogues; GLP-1 RA). They are currently widely used for the treatment of patients with type 2 diabetes mellitus owing to good antidiabetic efficacy, low risk of hypoglycemia, and relatively few other side effects. They also offer potential additional benefits such as weight neutrality or weight loss, positive effects on blood pressure and lipid levels, and potential cardio- and neuroprotectivity. Some experimental ...
Source: Drug Safety - November 13, 2014 Category: Drugs & Pharmacology Source Type: research

Multiple Drug Intolerance Syndrome: A Large-Scale Retrospective Study
Abstract Background The term multiple drug intolerance syndrome (MDIS) has been used to describe patients who express adverse drug reactions to three or more drugs without a known immunological mechanism. Objective To identify patient factors that could increase the risk of MDIS. Method Inpatient records over a 5-year period were captured from an electronic prescribing system to identify patients with at least one documented drug allergy. Univariable and multivariable analyses were used to compare the rates of MDIS...
Source: Drug Safety - November 2, 2014 Category: Drugs & Pharmacology Source Type: research

A Cross-Country Comparison of Rivaroxaban Spontaneous Adverse Event Reports and Concomitant Medicine Use with the Potential to Increase the Risk of Harm
Conclusion A large proportion of adverse event reports for rivaroxaban were associated with use of concomitant medicines, which may have increased the risk of adverse events—in particular, haemorrhage. Increased awareness of a patient’s comorbidity and associated medicine use is needed when rivaroxaban is used in clinical practice. (Source: Drug Safety)
Source: Drug Safety - November 1, 2014 Category: Drugs & Pharmacology Source Type: research

Liver Safety Assessment: Required Data Elements and Best Practices for Data Collection and Standardization in Clinical Trials
Abstract A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered es...
Source: Drug Safety - October 31, 2014 Category: Drugs & Pharmacology Source Type: research

Causality Assessment for Suspected DILI During Clinical Phases of Drug Development
Abstract Causality assessment is a critical step in establishing the diagnosis of drug induced liver injury (DILI) during drug development. DILI may resemble almost any type of liver disease, and often presents a serious challenge to clinical investigators and drug makers. The diagnosis of DILI is largely based upon a combination of a compatible clinical course, exclusion of all other reasonable causes, resemblance of clinical and pathological features to known features of liver injury due to the drug (i.e., “drug’s signature”), and incidence of liver injury among patients treated with the drug ...
Source: Drug Safety - October 31, 2014 Category: Drugs & Pharmacology Source Type: research

Evolution of the Food and Drug Administration Approach to Liver Safety Assessment for New Drugs: Current Status and Challenges
Abstract Prompted by approval in 1997 of troglitazone and bromfenac, two drugs that promptly began to show serious and sometimes fatal liver toxicity, we began at the Food and Drug Administration (FDA) a series of annual conferences in 1999 to consider issues of drug-induced liver injury (DILI). First inviting reviewers of new drug applications we opened the audiences in 2001 to pharmaceutical industry and academic consultants to industry and FDA, and slides shown at the meetings were posted on the internet to be available at the website of the American Association for the Study of Liver Diseases (AASLD)–go...
Source: Drug Safety - October 31, 2014 Category: Drugs & Pharmacology Source Type: research

Methodology to Assess Clinical Liver Safety Data
Abstract Analysis of liver safety data has to be multivariate by nature and needs to take into account time dependency of observations. Current standard tools for liver safety assessment such as summary tables, individual data listings, and narratives address these requirements to a limited extent only. Using graphics in the context of a systematic workflow including predefined graph templates is a valuable addition to standard instruments, helping to ensure completeness of evaluation, and supporting both hypothesis generation and testing. Employing graphical workflows interactively allows analysis in a team-base...
Source: Drug Safety - October 31, 2014 Category: Drugs & Pharmacology Source Type: research

The Clinical Liver Safety Assessment Best Practices Workshop: Rationale, Goals, Accomplishments and the Future
(Source: Drug Safety)
Source: Drug Safety - October 31, 2014 Category: Drugs & Pharmacology Source Type: research

Liver Safety Assessment in Special Populations (Hepatitis B, C, and Oncology Trials)
Abstract The FDA guidance for industry in the premarketing clinical evaluation of drug-induced liver injury (DILI) is the most specific regulatory guidance currently available and has been useful in setting standards for the great majority of clinical indications involving subjects with a low risk of liver disorders. However, liver safety assessment faces challenges in populations with underlying liver disease, such as viral hepatitis or metastatic cancer. This is an important issue because there are currently many promising anti-viral and oncologic therapies in clinical development, with a trend toward oral ther...
Source: Drug Safety - October 31, 2014 Category: Drugs & Pharmacology Source Type: research

Cardiovascular Risk with Non-steroidal Anti-inflammatory Drugs: Clinical Implications
Abstract In February 2014, the US Food and Drug Administration (FDA) convened an advisory committee meeting to discuss the accumulated data relating to the cardiovascular risk of non-steroidal anti-inflammatory drugs (NSAIDs) and the potential implications on the class prescription labeling. The committee recommended, though not unanimously, that (1) the current data does not support the conclusion that naproxen has a lower risk of thrombotic events than other NSAIDs; (2) there is no latency period for the risk of cardiovascular thrombotic events; (3) there are some patient populations at increased risk for event...
Source: Drug Safety - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

Erratum to: Adverse Gastrointestinal Events with Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors: Nested Case–Control Study
(Source: Drug Safety)
Source: Drug Safety - October 23, 2014 Category: Drugs & Pharmacology Source Type: research

Benefits and Risks of Using Smart Pumps to Reduce Medication Error Rates: A Systematic Review
Conclusion The literature suggests that smart pumps reduce but do not eliminate programming errors. Although the hard limits of a drug library play a main role in intercepting medication errors, soft limits were still not as effective as hard limits because of high override rates. Compliance in using smart pumps is key towards effectively preventing errors. Opportunities for improvement include upgrading drug libraries, developing standardized drug libraries, decreasing the number of unnecessary warnings, and developing stronger approaches to minimize workarounds. Also, as with other clinical information systems,...
Source: Drug Safety - October 8, 2014 Category: Drugs & Pharmacology Source Type: research

Compensation for Clinical Trial-Related Injury and Death in India: Challenges and the Way Forward
Abstract Clinical research, including clinical trials, is the bedrock of evidence-based medicine and is the most reliable method of generating credible data. Over the last decade, India has been one of the preferred destinations for clinical research activities. However, a couple of trials generated widespread media coverage due to alleged ethical transgressions, which generated debate among various stakeholders and dented the overall image of clinical research activities in the country. One of the major issues which has emerged is of compensation to research participants for clinical trial-related injury or death...
Source: Drug Safety - October 7, 2014 Category: Drugs & Pharmacology Source Type: research

Erratum to: Converting to a Common Data Model: What is Lost in Translation?
(Source: Drug Safety)
Source: Drug Safety - October 7, 2014 Category: Drugs & Pharmacology Source Type: research

Therapeutic Risk Management of Medicines
(Source: Drug Safety)
Source: Drug Safety - October 3, 2014 Category: Drugs & Pharmacology Source Type: research

Safety Profile of Dapagliflozin for Type 2 Diabetes: Pooled Analysis of Clinical Studies for Overall Safety and Rare Events
Conclusion Dapagliflozin has a favourable and predictable tolerability profile, with reported events related to its mechanism of action. (Source: Drug Safety)
Source: Drug Safety - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

International society of pharmacovigilance
(Source: Drug Safety)
Source: Drug Safety - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

The Safety of Olanzapine in Young Children: A Systematic Review and Meta-Analysis
Conclusions Most adverse events associated with olanzapine use in children less than 13 years of age are of minor clinical significance. These findings support the exploration of olanzapine for the prevention of CINV in children in future trials. (Source: Drug Safety)
Source: Drug Safety - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

Teaching Pharmacovigilance: the WHO-ISoP Core Elements of a Comprehensive Modular Curriculum
(Source: Drug Safety)
Source: Drug Safety - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

Comparison of Pregnancy and Lactation Labeling for Attention-Deficit Hyperactivity Disorder Drugs Marketed in Australia, the USA, Denmark, and the UK
Conclusion The study suggests that pregnancy and lactation labeling in PI for drugs marketed by the same pharmaceutical companies depend on the country of marketing; this raises concern about the reliability of PI documents as a useful source of information for appropriate prescribing during pregnancy and lactation. Discrepancies in this information can potentially lead to inappropriate prescribing in pregnant and breastfeeding women, who may expose their fetuses and breastfed children to unnecessary risks. At the same time, unjustified warnings against breastfeeding may result in children being unnecessarily we...
Source: Drug Safety - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

Pharmacovigilance for a Revolving World: Prospects of Patient-Generated Data on the Internet
(Source: Drug Safety)
Source: Drug Safety - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

Side Effects of Cytokines Approved for Therapy
Abstract Cytokines, currently known to be more than 130 in number, are small MW (
Source: Drug Safety - October 1, 2014 Category: Drugs & Pharmacology Source Type: research

Text Mining for Adverse Drug Events: the Promise, Challenges, and State of the Art
This article provides an overview of recent advances in pharmacovigilance driven by the application of text mining, and discusses several data sources—such as biomedical literature, clinical narratives, product labeling, social media, and Web search logs—that are amenable to text mining for pharmacovigilance. Given the state of the art, it appears text mining can be applied to extract useful ADE-related information from multiple textual sources. Nonetheless, further research is required to address remaining technical challenges associated with the text mining methodologies, and to conclusively determine the rel...
Source: Drug Safety - September 29, 2014 Category: Drugs & Pharmacology Source Type: research

Ranibizumab and Risk of Hospitalisation for Ischaemic Stroke and Myocardial Infarction in Patients with Age-Related Macular Degeneration: A Self-Controlled Case-Series Analysis
Conclusion This case-series analysis suggests an increased risk of hospitalisation for ischaemic stroke for patients receiving ranibizumab in the 31–60 days risk period. Studies with larger populations are required to confirm the risk in the 1–30 days risk period. No evidence of increased risk of hospitalisation for MI was observed. (Source: Drug Safety)
Source: Drug Safety - September 27, 2014 Category: Drugs & Pharmacology Source Type: research

Safety Profile of Biological Medicines as Compared with Non-Biologicals: An Analysis of the Italian Spontaneous Reporting System Database
Conclusions Most ADRs attributed to biologicals are ‘skin and subcutaneous tissue disorders’. Anticancer monoclonal antibodies are most frequently associated with ADRs. A low proportion of ADR reports concern biosimilars. (Source: Drug Safety)
Source: Drug Safety - September 26, 2014 Category: Drugs & Pharmacology Source Type: research

Stimulated Reporting: The Impact of US Food and Drug Administration-Issued Alerts on the Adverse Event Reporting System (FAERS)
Conclusions Our results suggest that most of modern day FAERS reporting is not significantly affected by the issuance of FDA alerts. (Source: Drug Safety)
Source: Drug Safety - September 26, 2014 Category: Drugs & Pharmacology Source Type: research

Relevance of Foreign Alerts and Newsletters for the Medication Errors Reporting Programme in The Netherlands: An Explorative Retrospective Study
Conclusion This study showed for a broad range of errors that the Dutch national reporting programme could learn from the three reporting programmes in Canada, the US and the UK. National reporting programmes can benefit from sharing alerts and newsletters that enhance the learning between countries. (Source: Drug Safety)
Source: Drug Safety - September 26, 2014 Category: Drugs & Pharmacology Source Type: research

Pharmacotherapy of Type 2 Diabetes Mellitus: An Update on Drug–Drug Interactions
Abstract The incidence of type 2 diabetes mellitus is increasing rapidly, as are the associated co-morbidities. Consequently, it has become necessary for a diabetic patient to take multiple medications at the same time to delay progression of the disease. This can put patients at an increased risk of moderate to severe drug interactions, which may threaten patients’ life or may deteriorate the quality of their life. Hence, managing drug–drug interactions is the cornerstone of anti-diabetic therapy. Most of the clinically important drug–drug interactions of anti-diabetic agents are related to thei...
Source: Drug Safety - September 24, 2014 Category: Drugs & Pharmacology Source Type: research

Comment on: Prescribing of Rosiglitazone and Pioglitazone Following Safety Signals Analysis of Trends in Dispensing Patterns in The Netherlands from 1998 to 2008
(Source: Drug Safety)
Source: Drug Safety - September 24, 2014 Category: Drugs & Pharmacology Source Type: research

Author’s Reply to Carracedo-Martínez E Comment on: “Prescribing of Rosiglitazone and Pioglitazone Following Safety Signals: Analysis of Trends in Dispensing Patterns in The Netherlands from 1998 to 2008”
(Source: Drug Safety)
Source: Drug Safety - September 24, 2014 Category: Drugs & Pharmacology Source Type: research

Pharmacovigilance in China: Current Situation, Successes and Challenges
Abstract With the integration of the global pharmaceutical economy and the gradual transformation of the healthcare insurance system in China, the legislative framework for a comprehensive regulatory system monitoring the whole process including drug development, manufacture, distribution and use has been established by the China Food and Drug Administration (CFDA) to ensure the safety and effectiveness of medication use. China has established a relatively comprehensive pharmacovigilance system covering regulation, organisation and technology from 1989 to 2014. As of 2013, one national centre, 34 provincial centre...
Source: Drug Safety - September 14, 2014 Category: Drugs & Pharmacology Source Type: research

Fidelity Assessment of a Clinical Practice Research Datalink Conversion to the OMOP Common Data Model
Conclusion CPRD can be accurately transformed into the OMOP CDM with acceptable information loss across drugs, conditions and observations. We determined that for a particular use, case CDM structure was adequate and mappings could be improved but did not substantially change the results of our analysis. (Source: Drug Safety)
Source: Drug Safety - September 4, 2014 Category: Drugs & Pharmacology Source Type: research

Converting to a Common Data Model: What is Lost in Translation?
(Source: Drug Safety)
Source: Drug Safety - September 4, 2014 Category: Drugs & Pharmacology Source Type: research

Restrictive Reimbursement Policies: Bias Implications for Claims-Based Drug Safety Studies
Abstract Restrictive reimbursement policies—including those based on non-formulary drug status and prior authorizations—can create situations in which patients’ use of prescription medications is not fully captured in administrative claims data. This can create bias in drug safety studies that depend solely on these data. An analysis in two Canadian provinces found that primary administrative databases captured only 61 % of dispensations of drugs for which restrictive reimbursement policies were in place. A subsequent simulation study found that, in certain circumstances bias due to exposure...
Source: Drug Safety - September 4, 2014 Category: Drugs & Pharmacology Source Type: research

Dosage Effects of Histamine-2 Receptor Antagonist on the Primary Prophylaxis of Non-Steroidal Anti-Inflammatory Drug (NSAID)-Associated Peptic Ulcers: A Retrospective Cohort Study
Conclusion High-dose H2RA showed greater effectiveness than low-dose H2RA in the primary prophylaxis of NSAID-associated PUs in short-term new users. (Source: Drug Safety)
Source: Drug Safety - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Cardiovascular Effects of Methylphenidate, Amphetamines and Atomoxetine in the Treatment of Attention-Deficit Hyperactivity Disorder: An Update
Abstract Several million children and a growing number of adults are currently being treated for attention-deficit hyperactivity disorder (ADHD) worldwide. Concerns have been expressed about possible cardiac effects of the common treatments, namely methylphenidate, amphetamines and atomoxetine. Small increases in mean heart rate (HR) and mean blood pressure (BP) have been reported for all three drugs, but most of the studies have not yielded statistically significant results. These studies also have limitations, particularly regarding the lack of accepted and standardised measurement methods. Several large studie...
Source: Drug Safety - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Tolerability and Safety of the New Anti-Obesity Medications
Abstract Worldwide obesity prevalence has nearly doubled since 1980. Due to numerous co-morbidities, obesity represents a serious health and socioeconomic problem worldwide. Pharmacotherapy should be an integral part of comprehensive obesity management. Drug therapy can assist in weight loss and its maintenance in those individuals who do not achieve appropriate weight loss through lifestyle interventions alone. After the withdrawal of sibutramine from the market in 2010, orlistat, a lipase inhibitor, was the only remaining prescription drug approved for the long-term treatment of obesity. In 2012, phentermine/to...
Source: Drug Safety - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Adverse Gastrointestinal Events with Intravitreal Injection of Vascular Endothelial Growth Factor Inhibitors: Nested Case–Control Study
Conclusions In this population-based study, intravitreal injections of bevacizumab and ranibizumab were not associated with increased risks of adverse GI events. (Source: Drug Safety)
Source: Drug Safety - September 1, 2014 Category: Drugs & Pharmacology Source Type: research

Drug-Induced Hyperkalemia
Abstract Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also i...
Source: Drug Safety - September 1, 2014 Category: Drugs & Pharmacology Source Type: research