Thèse d'exercice : Pharmacie : Université de Nantes : 2005. / Bibliogr. f. 89-91 [41 réf.].

Cancer survivors are at greater risk of cardiovascular diseases in comparison to the general population. Cardiovascular disorders are among the most prominent comorbidities in breast cancer patients. In order to gain a better understanding of the prescribing practices and cardiovascular risks associated with oncology drugs, this thesis encompasses a detailed review of the molecular and physiological mechanisms leading to drug‐induced cardiotoxicity and an evaluation of the cardiovascular risks associated with cancer drug therapies. Using a nested case‐control design, we evaluated whether these cancer drugs were associated with adverse cardiovascular outcomes under real‐world conditions of use. Although only few oncology drugs are indicated for breast cancer treatment, we were interested in prescribing practices and whether breast cancer treatments are restricted to labelled indications. The characterization of prescribing practices provides insights on the range of antineoplastic agents that should be considered in the evaluation of treatmentrelated adverse reactions such as cardiotoxicity. We found that selective estrogen receptor modulators demonstrated a better safety profile than aromatase inhibitors based on their mechanism of action on the cardiovascular system. These observations were corroborated by our findings from logistic regression analyses where aromatase inhibitors were associated with a higher risk of heart failure in a heterogeneous population of breast cancer patients. We reported that off‐label prescribing is common strategy in breast cancer treatment. While this practice tends to be associated with specific socio‐demographic and disease characteristics, the majority of off-label encounters are evidence‐based decisions. Because these off‐label treatments have their own inherent safety profiles, a comprehensive approach, covering all antineoplastic agents administered should be adopted in the evaluation of breast cancer treatment-induced cardiotoxicity. Careful monitoring of patients is crucial for the early detection of warning signs of cardiotoxicity to prevent long‐term deleterious effects. The information contained in this thesis provides useful considerations for the prospective surveillance of cancer drug‐induced cardiac events. These findings point to the need for a multi‐disciplinary approach to facilitate the rapid diagnosis and treatment of cardiac complications secondary to cancer therapy and to ensure that treatment decisions will maximize tumor response while minimizing adverse outcomes.

This thesis considers an approach to evaluate the effectiveness of risk communications for prescription drugs by performing interrupted time series analysis of prescription drug volumes prior to and after the risk communication date. The paper presents methods for detecting change in the presence of autocorrelation and techniques to reduce bias in estimation. Statistical results and data plots are presented for 63 data series. Size and power of the statistical techniques are considered, and a correspondence analysis between these statistical techniques and a small group of physicians is performed. The methods considered in this thesis correspond weakly with physician sentiment, and exhibit inflated type I errors in the presence of significant autocorrelation.

This thesis considers an approach to evaluate the effectiveness of risk communications for prescription drugs by performing interrupted time series analysis of prescription drug volumes prior to and after the risk communication date. The paper presents methods for detecting change in the presence of autocorrelation and techniques to reduce bias in estimation. Statistical results and data plots are presented for 63 data series. Size and power of the statistical techniques are considered, and a correspondence analysis between these statistical techniques and a small group of physicians is performed. The methods considered in this thesis correspond weakly with physician sentiment, and exhibit inflated type I errors in the presence of significant autocorrelation.

L’évolution du système de pharmacovigilance au Nigéria a été associée à une croissance modeste et les hôpitaux universitaires ont été identifiés comme des partenaires importants du système de pharmacovigilance. Cependant, aucune étude n'a encore été réalisée sur les performances du système de pharmacovigilance dans les hôpitaux universitaires nigérians. Cette étude visait à évaluer l'état de la pharmacovigilance, en particulier les réactions indésirables aux médicaments dans le sud et le sud du Nigéria, en se référant à des médicaments sélectionnés. Le système de pharmacovigilance ainsi que le schéma posologique des médicaments ont été évalués à l'aide des indicateurs de pharmacovigilance de base de l'OMS et des indicateurs de prescription de base de l'OMS, respectivement. Cela a été suivi d'une intervention éducative avec des messages texte envoyés via le système de messagerie courte (SMS) pour améliorer les connaissances, l'attitude et la pratique de la pharmacovigilance parmi les professionnels de la santé. Le nombre, la qualité et le profil des effets indésirables du médicament ont également été évalués avant et après l'intervention. Les facteurs probables susceptibles de contribuer à une mauvaise notification des problèmes de pharmacovigilance ont été recherchés en effectuant une enquête sur les connaissances, la sensibilisation et les pratiques des professionnels de la santé travaillant dans la zone. Ces faiblesses de la pharmacovigilance étaient essentiellement. Les résultats ont montré que des structures étaient en place pour les activités de pharmacovigilance, même si certaines étaient peu fonctionnelles. Les indicateurs de processus et de résultat / impact ont révélé des systèmes de santé faibles et une attention générale insuffisante à la pharmacovigilance dans les hôpitaux. Il a également montré que, même si le groupe possédait une connaissance modeste et une perception juste de la pharmacovigilance, la pratique était médiocre et peu de réactions indésirables au médicament étaient répertoriées dans les bases de données des hôpitaux locaux. Celles-ci ont été attribuées à une connaissance insuffisante de la pharmacovigilance sur ce qui peut être signalé, à des processus de notification médiocres, à de fausses croyances selon lesquelles leur notification ne fera aucune différence et à la difficulté de déterminer les éléments à signaler. Une perception insuffisante de l’intérêt de la notification des effets indésirables. Les connaissances et les pratiques en matière de pharmacovigilance se sont améliorées, de même que le nombre de déclarations d'effets indésirables au médicament suite à une intervention éducative. Cette étude a également mis en évidence le profil des effets indésirables associés aux médicaments couramment utilisés dans la zone et les problèmes inhérents à la notification spontanée. Il souligne également que la pharmacovigilance, discipline en pleine croissance, peut être améliorée par des évaluations fréquentes du système, la formation des professionnels de la santé et le renforcement général du système de santé nigérian. Des études plus approfondies seraient nécessaires pour mieux évaluer la sécurité des médicaments dans cette population noire homogène. / The evolution of the pharmacovigilance system in Nigeria has been associated with modest growth and teaching hospitals have been identified as important partners in the pharmacovigilance mechanism. However, there have been no studies evaluating the performance of the pharmacovigilance system in Nigerian Teaching hospitals prior to this time. This study set out to evaluate the state of pharmacovigilance specifically adverse drug reactions in South-South Nigeria. The pharmacovigilance system as well as the prescribing pattern of medicines was evaluated using the WHO Core Pharmacovigilance indicators and WHO Core Prescribing indicators respectively. This was followed by an educational intervention with text messages sent via the Short Messaging System (SMS) to improve the knowledge, attitude and practice of pharmacovigilance amongst healthcare professionals. The number, quality and profile of Adverse Drug Reactions (ADRs) were also assessed before and after the intervention. Factors likely to contribute to poor reporting of pharmacovigilance issues were sought by conducting knowledge, awareness, and practice survey of healthcare professionals working in the zone.The findings showed that of the six teaching hospitals assessed, only three could be described as functional or partly functional although all had some structures in place for pharmacovigilance activities. The process and outcome/impact indicators revealed weak health systems and overall insufficient attention to pharmacovigilance in the hospitals as only one centre had committed their ADR reports to the National Pharmacovigilance Centre and there were few documented medicines related admissions ranging from 0.0985/1000 to 1.67/1000 admissions. It further showed that although a modest knowledge and fair perception of pharmacovigilance existed among the group, practice was poor as only 12% of the 811 healthcare Professionals had ever used the national ADR reporting form and there were few adverse drug reaction reports in the local hospital databases. These were attributed to insufficient awareness of pharmacovigilance on what can be reported, poor reporting processes, wrong beliefs that their reporting will not make a difference and difficulty in determining what to report. There was an improvement in the knowledge and practice of pharmacovigilance, with a 31.6% increase in the number of adverse drug reaction reports following an educational intervention. This study also highlighted the ADR profile to commonly used medicines in the zone and the inherent problems associated with spontaneous reporting. It further highlights that the growing discipline of pharmacovigilance can be improved through frequent assessments of the system, training of the healthcare professionals and general strengthening of the Nigerian healthcare system. More in-depth studies would be required to further evaluate the safety of medicines in the Nigerian population.

Magister Public Health - MPH / Background: Healthcare providers are critical to collecting information on drug safety and successful adverse drug reaction (ADR) reporting. The roles of doctors and pharmacists have been recognized as important to voluntary ADR reporting and their roles are consistently being investigated. However, despite the strategic role of nurses in medicine administration, their role in ADR reporting has not been widely explored, particularly in sub-Saharan African countries. Aim: To assess the knowledge, attitudes and practice of ADR reporting amongst nurses in Lagos University Teaching Hospital (LUTH), a tertiary hospital located in Lagos; the economic centre of Nigeria, as well as the most populous city in the country. Methodology: A cross-sectional descriptive survey with analytical components was conducted among nurses in a tertiary institution. All nurses working in major specialties - out-patients’ clinics, theatre and clinical wards in the facility, were eligible to participate in the study. Student nurses undergoing training or postings in the facility were excluded from the study. A sample size of 124 nurses was calculated using OpenEpi sample size calculator based on an estimated study population of 400 with a 95% confidence interval and an assumed 5% of nurses reporting an ADR based on National Pharmacovigilance Centre database. A sample of 140 nurses was selected in an attempt to realize sample. Cluster sampling was used to randomly select clinics and wards and all nurses in the selected clusters were included in the study. A structured questionnaire consisting of close-ended questions was used. It comprised sections on nurses’ characteristics, knowledge of pharmacovigilance concepts, attitudes towards ADR reporting, and barriers to and practice of ADR reporting. Data collected were entered into an Excel spreadsheet and imported to the SPSS version 20 software for analysis. Descriptive analyses were conducted on all the variables and cross-tabulation between selected variables was explored to test for statistical significance using chi-squared test.

With the phenomenal growth of digital devices coupled with their ever-increasing capabilities of data generation and storage, sequential data is becoming more and more ubiquitous in a wide spectrum of application scenarios. There are various embodiments of sequential data such as temporal database, time series and text (word sequence) where the first one is synchronous over time and the latter two often generated in an asynchronous fashion. In order to derive precious insights, it is critical to learn and understand the behavior dynamics as well as the causality relationships across sequences. Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse drug reactions (ADR) or other drug-related problems. In the post-marketing phase, the effectiveness and the safety of drugs is monitored by regulatory agencies known as post-marketing surveillance. Spontaneous Reporting System (SRS), e.g., U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), collects drug safety complaints over time providing the key evidence to support regularity actions towards the reported products. With the rapid growth of the reporting volume and velocity, data mining techniques promise to be effective to facilitating drug safety reviewers performing supervision tasks in a timely fashion. My dissertation studies the problem of exploring, analyzing and modeling various types of sequential data within a typical SRS: Temporal Correlations Discovery and Exploration. SRS can be seen as a temporal database where each transaction encodes the co-occurrence of some reported drugs and observed ADRs in a time frame. Temporal association rule learning (TARL) has been proven to be a prime candidate to derive associations among the objects from such temporal database. However, TARL is parameterized and computational expensive making it difficult to use for discovering interesting association among drugs and ADRs in a timely fashion. Worse yet, existing interestingness measures fail to capture the significance of certain types of association in the context of pharmacovigilance, e.g. drug-drug interaction (DDI) related ADR. To discover DDI related ADR using TARL, we propose an interestingness measure that aligns with the DDI semantics. We propose an interactive temporal association analytics framework that supports real-time temporal association derivation and exploration. Anomaly Detection in Time Series. Abnormal reports may reveal meaningful ADR case which is overlooked by frequency-based data mining approach such as association rule learning where patterns are derived from frequently occurred events. In addition, the sense of abnormal or rareness may vary in different contexts. For example, an ADR, normally occurs to adult population, may rarely happen to youth population but with life threatening outcomes. Local outlier factor (LOF) is identified as a suitable approach to capture such local abnormal phenomenon. However, existing LOF algorithms and its variations fail to cope with high velocity data streams due to its high algorithmic complexity. We propose new local outlier semantics that leverage kernel density estimation (KDE) to effectively detect local outliers from streaming data. A strategy to continuously detect top-N KDE-based local outliers over streams is also designed, called KELOS -- the first linear time complexity streaming local outlier detection approach. Text Modeling. Language modeling (LM) is a fundamental problem in many natural language processing (NLP) tasks. LM is the development of probabilistic models that are able to predict the next word in the sequence given the words that precede it. Recently, LM is advanced by the success of the recurrent neural networks (RNNs) which overcome the Markov assumption made in the traditional statistical language models. In theory, RNNs such as Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) can “remember� arbitrarily long span of history if provided with enough capacity. However, they do not perform well on very long sequences in practice as the gradient computation for RNNs becomes increasingly ill-behaved as the expected dependency becomes longer. One way of tackling this problem is to feed succinct information that encodes the semantic structure of the entire document such as latent topics as context to guide the modeling process. Clinical narratives that describe complex medical events are often accompanied by meta-information such as a patient's demographics, diagnoses and medications. This structured information implicitly relates to the logical and semantic structure of the entire narrative, and thus affects vocabulary choices for the narrative composition. To leverage this meta-information, we propose a supervised topic compositional neural language model, called MeTRNN, that integrates the strength of supervised topic modeling in capturing global semantics with the capacity of contextual recurrent neural networks (RNN) in modeling local word dependencies.

>Magister Scientiae - MSc / Introduction: Medicines are created with the intention of helping patients but may be harmful to the patient by causing adverse reactions. The effect of adverse drug reactions (ADRs) on patients has become more evident over the last two decades and reporting of ADRs in South Africa is low. This results in many patients, particularly children, potentially being exposed to medicinal products with an uncertain safety profile. Due to parents’ typical caring and protective role, they could play a part in detecting and reporting ADRs in children, thereby contributing to making safer medicines available to children. Aim: This research study evaluated the awareness and knowledge in South Africa of parental reporting of suspected ADRs in their children. Method: A quantitative descriptive study was conducted based on an anonymous web-based self-administered questionnaire that was distributed through Facebook® and LinkedIn™ to parents in South Africa. The questionnaire, which was distributed between July 2018 and August 2018, was standardized for all participants and consisted of closed (n=28) and open-ended (n=4) questions. The questions were coded, data was analysed using descriptive statistics (percentage and frequency counts). Associations between categorical demographic variables were determined using the Pearson Chi-square test. Results: The questionnaire was voluntarily completed by 206 participants. Majority of the respondents were female (n=155, 75.2%) and the most relevant age category for all respondents was 31-40 years (n=100, 48.5%). The majority of participants (n=146, 70.9%) were aware of the term ADR and significant associations between awareness of ADRs and ethnicity, marital status, education level, medical aid and access to general medical services were found. Being white (p<0.001), having a degree (p=0.001) and having private medical aid (p=0.004) were independently associated with being significantly more aware of the term ADR compared to being black (p<0.001), coloured (p=0.004), a single parent (p=0.003), not finishing school (p<0.001), having matriculated (p<0.001), having no private medical aid (p=0.004) and receiving general medical services from public clinics (p = 0.003).

Reproduction de : Thèse d'exercice : Pharmacie : Nantes : 2009. / Bibliogr.

Made available in DSpace on 2014-06-11T19:28:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-22Bitstream added on 2014-06-13T20:36:55Z : No. of bitstreams: 1 varallo_fr_me_arafcf.pdf: 2844690 bytes, checksum: 3c22713b3171e234e431e8c9717a455d (MD5) / Reações Adversas a Medicamentos (RAM) são um importante problema de saúde pública, pois reduzem a qualidade de vida do paciente e geram gastos desnecessários aos hospitais. Por isso, o presente estudo estimou a prevalência de internações hospitalares por possível RAM, identificou o perfil demográfico dos pacientes acometidos, bem como os fármacos e as possíveis RAM mais frequentemente relacionadas com as internações hospitalares. Para tanto, realizou-se um estudo observacional e transversal na clínica médica de um hospital de ensino, entre os meses de agosto a dezembro de 2008. Os pacientes foram entrevistados sobre os sintomas/queixas/motivos de internação que os levaram ao hospital e quais medicamentos utilizaram nos 15 dias prévios à internação. Durante o período do estudo, observou-se que a internação hospitalar estava relacionada com possível RAM em 115 pacientes (46,4%), sendo a maioria mulheres e não-idosos. Os fármacos mais frequentemente relacionados com a internação foram os que atuam nos sistemas: cardiovascular (48,7%), digestório (22,9%) e nervoso central (14,1%). Quanto ao tipo de receituário dos medicamentos responsáveis por RAM, 90,9% eram sob prescrição, sendo que 9,4% eram sujeitos a controle especial e 9,1% eram isentos de prescrição. Dos medicamentos responsáveis pelas internações, 58% pertenciam à lista RENAME. Em relação aos idosos, 43,9% utilizaram medicamentos impróprios, os quais foram possivelmente responsáveis pela internação de 29,2% pacientes. As manifestações clínicas das RAM mais comuns foram: do aparelho digestório (23,0%), dos aparelhos respiratório (20,2%) e circulatório (14,6%), além de sintomas, sinais e achados anormais de exames clínicos e laboratoriais (20,2%). Apenas a polimedicação foi detectada como fator de risco para internações por possível RAM. Estudos farmacoepidemiológicos como este... / Adverse Drug Reaction (ADR) is an important public health concern, because they decrease the patient’s quality of life and raise the unnecessary expenditure for the hospital. The purpose of this study was to: 1) assess the prevalence of ADR-related admission; 2) identify the demographic characteristics of the patients with ADR; 3) identify the main drugs and the ADR more often associated with hospitalization. A cross-sectional observational study was performed. It was conducted in an internal medicine ward in a teaching hospital and the data was collected from August 2008 to December 2008. The patients were interviewed about their symptoms, complaints, and causes of hospitalization, which were responsible to the hospital admission and what were the drugs used 15 days prior the hospitalization. During the period of the study, it was observed ADR-related admission in 115 (46.4%) patients; the majority was woman and no-elderly. Medications that were commonly involved in these cases were those acting on the cardiovascular (48.7%), gastrointestinal (22.9%) and nervous system (14.1%). Regarding the type of prescription medicines, 90.6% were under prescription, of these 9.4% still were subjected to special control, and 9.1% were non-prescription drugs. 58.0% medicines ADR-related admission belonged to RENAME’s list. Considering the elderly people, 43.9% of them used inappropriate drugs, which were possibly responsible for hospitalization in 29.2% patients. The clinical manifestations of RAM most commonly associated with the hospitalization were: gastrointestinal system (23.0%), abnormal findings in clinical and laboratory tests (20.2%), respiratory system (20.2%) and circulatory system (14.6%). Only polipharmacy was detected as a risk factor for ADR-related admission. The present pharmacoepidemiological study shows the need of patient’s therapeutic monitoring in the first... (Complete abstract click electronic access below)