Day 2 :
- Drug Safety | Pharmacy Practice & Challenges | Preclinical & Clinical Trials
Location: Conference Room 4
Helsinki University Hospital, Finland
Universidad de la República, Uruguay.
Title: Is Carnitine deficiency the cause of higher ammonia levels in patients under Valproic acid treatment and in the elderly?
Time : 10.00-10.30
Cecilia Maldonado has completed her PhD on Efflux Transporters and its Relationship to Anticonvulsants Therapeutics. She is Assistant Professor at the Pharmaceutical Sciences Department in the Faculty of Chemistry, Uruguay and a researcher at the University Hospital in the Therapeutic Drug Monitoring Service. She has published more than 15 papers in reputed journals and was awarded the Grant for Professional Innovation from the International Pharmaceutical Federation (FIP) in 2013.
Higher ammonia levels have been associated with valproic treatment, some central nervous system pathologies and age. Serum carnitine and/or acetylcarnitine depletion have been postulated in the literature as possible causes. To analyze if this deficiency could result in increased ammonia levels three groups of patients were studied: A) epileptic under phenytoin treatment; B) with bipolar disorder under valproic acid treatment; C) elderly. Plasma valproic acid concentration (Group B), blood carnitine and acyl carnitine profiles, and ammonia blood concentrations in the three groups were determined. Patients in Groups B and C showed significant higher levels of ammonia than in Group A. Patients in Group B and with hyperammonemia presented significant lower acetylcarnitine levels and a trend towards lower carnitine levels than in Group A. Patients in Group B with normal values of ammonia presented significant higher values of both carnitine and acetylcarnitine than Group A. While mean carnitine levels in the elderly were significantly higher than in younger adults, mean acetylcarnitine levels were significantly lower. In patients treated with valproic acid, carnitine depletion followed by acetylcarnitine decrease could be responsible for the increase in the ammonia levels. In the elderly population, serum carnitine was probably increased due to impaired access to tissues which in turn resulted in acetylcarnitine decrease. This last fact could lead to ammonia impaired elimination. Exogenous administration of acetylcarnitine could be a promising agent to reverse higher ammonia levels.
Ain Shams University, Egypt
Title: Limited value of relative risk reductions for assessing the benefits of disease-modifying therapies for multiple sclerosis
Time : 10.30-11.00
Graduate of faculty of medicine Ain Shams university 1980. Resident in the neuropsychiatric department of Ain Shams University till 1984. Masters degree in neuropsychiatry 1984. Assistant lecturer of neurology till MD degree in neurology 1989. Lecturer of neurology from 1989 till 1994. Assistant professor of neurology from 1994 till 1999. Professor of neurology, faculty of medicine Ain Shams University since 1999 till now. Head of the multiple sclerosis unit of Ain Shams University since 2014. Currently the head of the neuropsychiatric department of Ain Shams University since August 2015. –Member of the MENACTRIMS assembly board.
The relative risk reduction ( RRR) is the main statistical parameter used to express the different primary outcomes of the clinical drug trials. Physicians often assume that a drug with a higher RRR demonstrated in one trial is more effective than a drug with a lower RRR demonstrated in another trial, and may pass this idea on to younger physicians and to the patients. The use-of the RRR as a measure of drug efficacy can be misleading as it depends on the nature of the population studied. The value of the RRR depends on the placebo event rate : A low RRR can be clinically meaningful if the event rate in the placebo group is high, while a high RRR can be clinically less meaningful if the event rate in the placebo group is low. Direct head to head comparison trials are the only way to assess the relative efficacy of the different drugs. The aim of this presentation is to correct this misconception.
Helsinki University Hospital, Finland
Time : 11.15-11.45
Dr. Lasse Lehtonen (born 1962) works as the administrative chief physician of the Helsinki University Hospital in Helsinki. After graduating from medical school in 1986 Dr. Lehtonen made his Ph.D. in transplantation immunology in the University of Turku and specialized for clinical pharmacology. In addition of medical training he has a doctors degree in law from the University of Helsinki, where he now is a part time professor. Dr. Lehtonen has authored or co-authored over 200 publications in immunology, clinical pharmacology or medical law with special interests in patient safety issues.
Our objective was to develop a method for identifying high-alert medications in a Finnish university hospital (HUS) by using medication error (ME) and near miss reports gathered through the hospital’s ME reporting system. Altogether 18 136 MEs and near misses were reported in 2007–2013. This study targeted to the reports where medications were coded as a contributing factor. Therapy groups and individual medications were identified. These were compared to the hospital’s drug consumption and Institute for Safe Medication Practice’s (ISMP) List of High-Alert Medications, which is probably the most widely used high-risk medication list. The reports including most reported and high-alert medications (120 reports) were qualitatively analysed by applying the simplified root cause analysis. The total sample included 249 reports with 280 medications of which 34% were ISMP’s high-alert medications. The therapeutic groups most commonly related to MEs were antibacterials for systemic use (13%), psycholeptics (10%), analgesics (9%), antithrombotic agents (9%) and anaesthetics (7%). Serious patient harm was related to cefuroxime, enoxaparin, ibuprofen, midatsolam, propofol and warfarin. A half of the MEs were related to parenteral preparations. Typical ME types were administration (34%), dispensing (18%), prescribing (15%), and documenting (15%) errors. The qualitative method deepened the understanding about key safety risks with high-alert medications, drug nomenclature, formulations and administration routes, and changes in the formulary. Combining qualitative and quantitative methods resulted in deeper insight when hospital-specific high-alert medications were identified. We identified several high-alert medications with quantitative methods, but qualitative method deepened the understanding about their key safety risks in the medication-use process.
A D John completed BA from Harvard University and MD from New York Medical College. He has undergone training in Internal Medicine at MetroWest Medical Center, Framingham; MA and Residency in Anesthesia and Critical Care Medicine at Johns Hopkins Hospital in Baltimore, MD; and a Fellowship in Cardiac Anesthesiology at the Massachusetts General Hospital in Boston, MA. He is an Assistant Professor of Anesthesiology and Critical Care Medicine at the Johns Hopkins University School of Medicine in Baltimore, MD. He is Co-editor with Sancho Rodriguez Villar for the publication, “Protocols in Critical Care” and Editor for “Essential Clinical Updates for Providers”.
The perioperative period is a time of increased risk. While under surgery the patient is not able to communicate and the body is being subjected to a variety of new stresses. Acute inflammatory mediators are being released during surgery, both acute and chronic pain processes are activated, patients have fluctuating levels of consciousness and their ability to accurately verbalize their needs may be hampered. The need to rapidly administer medications, facilitate throughput, and ensure rapid turnover places an extra level of urgency and risk for both the patient and healthcare provider. It is during this period that the risk of inadvertent administration of either an incorrect medication or incorrect dose poses the most difficulty. So, during this period what can be done to minimize this risk and ensure patient safety? In addition, how can the needs of efficiency and facile throughput be reconciled with patient safety ?
Alexandria University School of Medicine, Egypt
Time : 12.15-12.45
Dr ElHabachi is a Professor in the Department of Physiology and the Academic Director of the Alexandria Clinical Research Centre in the Faculty of Medicine, Alexandria University, Egypt. She is a multilingual Professor with a track record of establishing multinational partnerships, and teaches in both English and French. She has been pivotal in establishing the University Clinical Research Centre. Part of her pre-doctoral training was conducted in the Heart Science Centre, Imperial College, UK. In May 2006 she studied clinical research and GCP,University of Maryland USA. She has a broad research experience in national and international projects.
Alexandria CRC is the first center for clinical trials in Egypt. It was established in July 2006 with the assistance of the University of Maryland, USA, under the twining agreement between the cities of Alexandria and Baltimore. Trials are conducted according to ICH-GCP guidelines after approval of Research Ethics Committee (REC) of Alexandria Faculty of Medicine & Egyptian Ministry of Health (MOH). The center provides a full range of resources and services directly or in coordination with the institutional resources of Alexandria University Hospital: research patient care, trained research personnel, lab facilities, statistical consultation, computer and data management support. Our mission is to enhance and expand the magnitude of high-quality & ethical clinical research and avoid exploitation of research subjects. Our vision is upgrading Alex CRC to be a Center of Excellence in Clinical Research. Our objectives are to foster more innovative, high-impact clinical trials and to streamline drug development activities enabling Egyptian patients to access the best medical care, to train local/regional researchers to conduct multinational trials and other health research projects and assume leadership within the MENA region. Also, to integrate all parties involved such as MOH, WHO, academia, pharmaceuticals, CROs and RECs in Egypt into one extensive network for clinical trials. Our research activities are investigator-initiated & industry-sponsored phase II, III&IV multicenter trials. Educational activities include training courses on GCP & research ethics for investigators, research coordinators and REC members, in English and French. Our future plans include obtaining CAP accreditation to the CRC laboratory, establishing a clean area for the optimum preparation of cytotoxic drugs, setting up database registry for clinical trials in Egypt, designing clinical research programs that meet the international standards, granting certified degrees in clinical research and assisting the establishment of other local and regional clinical research centers. Challenges regarding research subjects, investigators, REC, regulatory authorities, sponsors and local facilities as well as our ways to overcome them will be discussed.
Alkharj Military Industries Corporation Hospital, Saudi Arabia
Time : 14.45-15.15
Zayed Nama Alsulami is a paediatric clinical pharmacologist working for Alkharj Military Hospital in Alkharj City, Saudi Arabia. Zayed has completed his PhD from University of Nottingham in 2013. His main role is to conduct research into paediatric drug therapy and medication errors including the medication errors in the Middle East countries, Nurses adherence to double check process and medication administration errors in children.
Children are more susceptible to medication errors than adults. Medication administration process is the last stage in the medication treatment process and most of the errors detected in this stage. Little research has been undertaken about medication errors in children in the Middle East countries. This study was aimed to evaluate how the paediatric nurses adhere to the medication administration policy and also to identify any medication preparation and administration errors or any risk factors. An observational, prospective study of medication administration process from when the nurses preparing patient medication until administration stage (May to August 2014) was conducted Saudi Arabia. Twelve paediatric nurses serving 90 paediatric patients were observed. 456 drug administered doses were evaluated. Adherence rate was variable in 7 steps out of 16 steps. Patient allergy information, dose calculation, drug expiry date were the steps in medication administration with lowest adherence rates. 63 medication preparation and administration errors were identified with error rate 13.8% of medication administrations. No potentially life-threating errors were witnessed. Few logistic and administrative factors were reported. The results showed that the medication administration policy and procedure need an urgent revision to be more sensible for nurses in practice. Nurses’ knowledge and skills regarding to the medication administration process should be improved.
Andaman & Nicobar Islands Institute of Medical Sciences, India
Title: Analysis of off-label use of drugs among pediatric inpatients of a tertiary care teaching hospital
Time : 15.15-15.45
Dr. Mangesh Bankar has completed his M.D. in Pharmacology from Government Medical College, Nagpur in 2006. Currently he is working as an Associate Professor in Department of Pharmacology of Andaman & Nicobar Islands Institute of Medical Sciences. He has published 10 papers in various national and international journals. He has presented research papers in three International Conferences. He is also working as a member of Institutional Ethics Committee of Shravan Hospital, Nagpur. He is reviewer and member of scientific advisory board of International Journal of Basic and Clinical Pharmacology. Beside that he is a good badminton player and regularly participate in various state level competitions.
Introduction: Off-label use of drugs refers to use of approved drugs in a situation that is not mentioned in the product information. As considerable risks are involved to the children and the extent of “off-label” drug use among children in India is largely unknown due to limited studies, this study was planned to determine the extent of off-label drug use in children admitted in a pediatric wards of a tertiary care teaching hospital. Material and Methods: This was a prospective, observational exploratory study in which data were collected from prescription records of all patients admitted between June and August 2014, in pediatric wards of Government Medical College, Nagpur. Results: Data were collected from 200 patients admitted in pediatric wards, all of them received at least two or more drugs. Of 1188 prescriptions, 524 (44.10%) were found off-label. The anatomical therapeutic chemical classes most involved in off-label prescriptions were anti-infectives for systemic use (45.03%), alimentary tract and metabolism (17.55%), Nervous system (13.74%) and Blood and blood forming organs (9.92 %). The highest rate of off-label drug prescriptions was observed in the age range of 1-30 days (36 %) followed by age range of 1-12 months (22.51%).Conclusions: The study found a high percentage of off-label use of drugs in the Pediatric inpatients. We identified inappropriate prescriptions for specific drug classes. The findings emphasize a need for further clinical studies as well as compilation of existing clinical experience and scattered evidence, particularly for drug treatment in pediatric population.
- Young Researchers Forum
Location: Conference Room 4
Julia Laín-Abril is a PharmD student graduated in CEU San Pablo University in Spain, and postgraduate alumna from University College London, obtaining distinction in the MSc in Drug Discovery and Pharma Management at the School of Pharmacy; she is also trained in Clinical Trials Management and Regulatory Compliance at University of Chicago. She has participated in the X National Undergraduate Congress in Health Sciences in Spain to present her work on “Current status of the ethical codes in the Official Schools of Pharmacists of Spain”. Today she works as a Product Stewardship and Regulatory Affairs Scientist in London.
Counterfeit drugs are a worldwide issue and its impact on public health is very well documented, being responsible for not only resistance to medicines but also patient deaths. Regulatory authorities are responsible for ensuring patients’ safety through the establishment of regulations that protect the four basic bioethical principles (autonomy, beneficence, non-maleficence and justice) and fighting against the counterfeit market. It is a fact that Internet has increased the breaches in the supply chains of highly regulated markets through online pharmacies that may be illicit or poorly regulated. The WHO states that medicines obtained from illegal Internet sites that hide their physical address are counterfeit in over a 50% of the cases. After studying the measures taken by regulatory authorities to ensure the safety of medicines and carefully analysing the current bioethical situation of the online market, it has been observed that Internet does not have an ethical code and most anti-counterfeit actions taken are focused on increasing the awareness of the consumer, reassuring the principle of autonomy. However, there are no actions detected to protect the principles of beneficence, non-maleficence and justice. It is suggested that further online anti-counterfeit measures focus on avoiding the reach of counterfeits to the online market instead of solely warning the consumers to prevent the purchase. For this, it will be necessary the collaboration of different parties - regulatory authorities, pharmaceutical companies, healthcare professionals, patients, government, police and customs - as well as a stronger will to promote an ethical online behaviour.
University of Genoa, Italy
Time : 16.15-16.30
Dr. Silvia Leone MD graduated in 2010 with the highest honours (summa cum laude) and an Academic Medal at the age of 24 from Genoa University. She is now attending her final year at the post-graduate School in Toxicology and Clinical Pharmacology in Genoa. She is working in the A&E Dept. of Galliera Hospital in Genoa. She has been working as an Emergency Doctor since January 2014 and has been cooperating with the main Alcohological Centre in Liguria Region since 2011. She has published 30 papers as Author or Co-Author, and has attended around 20 Congresses all over the world, presenting approximately 15 Posters. She was Speaker at the BTS Congress (British Toxicology Society) in Birmingham (2015), and in Turin at the Simeu (the Italian Society of Emergency Medicine) Congress (October, 2014). She has just gained the title of "Cruise Chief Doctor" (July 2016), after an Italian competitive exam held in Rome, Italy (Ministry of Health).
Background: Up to 25% of people in the U.S. experience angioedema and/or urticaria in their lifetimes, accounting for over 1 million ED visits each year. There are two key aetiologies of angioedema: histamine-mediated (acquired) and bradikinin-mediated (hereditary). Any potential lack of awareness can lead to treatment errors and poor outcomes for patients presenting with bradikinin-mediated angioedema.
Objectives: To recognize hereditary angioedema which needs a specific treatment; to discuss the pharmacological differences between C1-inhibitors (Berinert ®) and Icatibant for the treatment of hereditary angioedema.
Methods: All cases of hereditary angioedema were registered for a period of 1 year (2015) in the Emergency Dept. of Galliera Hospital (Genoa, Italy), using a Program called ‘PIESSE’. After this period the data were analyzed, and some considerations were made: the ability to make a prompt diagnosis of hereditary angioedema, and, in particular, the differences between the use of C1-inhibitors and Icatibant.
Results: We observed a total of 39 cases of angioedema. 11 of them were bradikin-mediated. We are glad to point out that all the hereditary angioedemas were recognized immediately by the Medical Doctors due to a particular awareness of this kind of disease. 6 cases were treated with Icatibant, and 5 with C1-inhibitors (Berinert ®).
Conclusion: Both drugs are effective in treating hereditary angioedema, but C1-inihibitors must be administered at higher doses (about 20 U/kg) endovenously in recognized hereditary angioedemas only. They have a human origin (this fact affects their safety), they must be stored in a refrigerated box, and their half-life is very long (approximately 87 hours). Icatibant can also be used in cases of suspected hereditary angioedema; it has a synthetic origin (safer), it can be stored anywhere, and its administration uses pre-filled syringes subcutaneously. It has the great advantage that it can be used by patients themselves who know to be affected by hereditary angioedema. Both drugs are able to relieve symptoms quickly. In our experience Icatibant is better than C1-inhibitors, especially in an Emergency Dept., although the use of Icatibant must be related to a complete knowledge of how to distinguish hereditary from acquired angioedema.
University of Buenos Aires, Argentina
Boscolo Oriana is finishing his third year doctoral scholarship from the University of Buenos Aires “Galenic and analytical development of orphan formulations applied to ursodeoxycholic acid therapy in children”; Assistant Laboratory technique; Researcher at the Centre for Research, Development and Pharmaceutical Control (CIDEC), Pharmaceutical Technology Department; grade teacher as an assistant with exclusive responsibility at Pharmaceutical Technology Department; 2 publications in international journals; 3 published abstracts; 7 presentations at scientific congress; 1 unit in book chapter; 3 attending congress; 6 courses graduate;
Ursodeoxycholic acid (UDCA), is a bile acid used to dissolve gallstones and for the treatment of hepatobiliary diseases. It is the only drug approved by the FDA for the treatment of primary biliary cirrhosis.
In UDCA raw material other bile acid may be present as impurities. Some of them, like lithocholic acid (LCA) is highly toxic, and others are associated with several side effects such as chenodeoxicholic acid (CDCA). USP Pharmacopeia describes the determination of CDCA and LCA by TLC, where each impurity limit should be not more than 1.5% and 0.02% respectively.
The aim of this work was to developed, and validated an analytical method by HPLC-UV for the determination of UDCA in oral liquid pharmaceutical formulations for pediatrics administration. Also, determined the impurities present in the raw material by HPLC / MS-MS.
HPLC-UV system was applied a C18 Symmetry column (150 mm x 4,6 mm id, particle size 3,5 µm, Waters), mobile phase ACN: H2O pH 3 (48:52), column temperature 40° C, flow rate 1 mL/min, injection volume 100 µL and detection UV 200 nm.
In the determination of impurities the chromatography method was carried isocratically at 25° C, using a column C18 Symmetry, mobile phase methanol:acetonitrile:10mM ammonium acetate buffer (40:40:20), flow rate 0.4 mL/min. Negative polarity and SRM mode were set for MS detection. The parameters optimized were: voltage; sheat gas pressure and tubulence offset.
Both methods were validated in terms of specificity, LOD, LOQ, linearity, precision, accuracy and robustness.
The developed methods meet specifications and are suitable for quality control.