Magister Pharmaceuticae - MPharm / In this study, the researcher wanted to determine the effect of dossier farming in medicine registration in South Africa by comparing the number of generic registrations of products tendered for the government for the molecules enalapril, amlodipine and losartan, before and after innovator patent expiration and quantified the extent it is practiced and how it affected medicine registration backlog.

Analysis of the Effect of Pharmacotherapy on the Risk of a Fall I. Author: Klára Šturcová1 Tutor: Josef Malý1 1 Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University in Pague Introduction: Falls of hospitalized patients are one of the most common problems in health institutions. In terms of prevention of falls it is necessary to analyze all the factors that might have contributed to the emergence of a fall and subsequently minimize these risk factors. Objectives: The aim of the thesis was to analyze the possible drugs and other causes of falls of patients hospitalized in a certain rehabilitation institution. Methods: The data were collected from 21 March to 31 July 2014 in an institution providing rehabilitation care. The evaluated group consisted of patients who fell during the hospitalization in this period. The data about the fall, personal and drug anamnesis were transferred to an electronic form and subsequently evaluated by means of the frequency analysis, converted into graphs and tables and discussed. Results: 67 patients experienced 79 falls. Women experienced 53 % of falls; men experienced 47 % of falls. 87 % of the patients fell once, 9 % of the patients fell twice, 4 % of the patients fell three times. 58 % of all falls were experienced by...

Analysis of the effect of pharmacotherapy on the risk of falls in inpatents III Author: Tereza Honsová Tutor: PharmDr. Josef Malý, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction: Falls are frequent and unwanted events happening in healthcare facilities. The falls have a multifactorial character. The prevention is the best way how to improve a quality of healthcare and a quality of the patient's life. All of the doctors, clinical pharmacists and nurses can help to realize it by cooperating with each other, working with professional information and by individual attitude to each patient. Objective: The aim of this study was to analyze the effect of the fall risk-increasing drugs to falls in hospitalized patients and to recommend the right interventions to prevent the fall. Methodology: For the analysation, classification and quantification of the fall risk-increasing drugs, drug related problems and interventions a special online database was created. All of the doctors, clinical pharmacists and nurses were collecting details about the pacients and about how the fall happened. Fall risk-increasing drugs and drug-related problems were then analyzed by clinical pharmacists. Potential interventions were suggested. Also other...

Analysis of the effect of pharmacotherapy on the risk of fall in inpatients II Author: Nikola Szikorová Tutor: PharmDr. Josef Malý, Ph.D. Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Introduction and objectives: Falls are one of the most common problems of hospitalized patients. Their occurrence is associated with many problems and therefore should be avoided. Effective prevention involves analyzing risk factors and implementing interventions to minimize these risks. The aim of this work was to analyze the influence of drugs and other risk factors on the fall of hospitalized patients. Methods: Data was collected from April to December 2017 in 4 hospitals in South Bohemia. Only patients who had fallen during hospitalization participated in the study. An online database was created for the study to collect patient data (personal history, medications used, laboratory values and others). Population and individual fall risk-increasing drugs were analyzed. For each individual fall risk-increasing drug, the type of drug problem that could have been the cause of a fall was classified. Risk minimization interventions have been assigned to each drug problem. In addition to fall risk-increasing drug analysis, other risk factors that increased the risk...

Although sensation-seeking status is associated with age of initiation and amount of drug use among adolescents, and sensitivity to the behavioral and reinforcing effects of drugs among young adults, it is unclear whether sensation-seeking status among adolescents is predictive of sensitivity to the pharmacological effects of drugs (i.e. abuse potential) as adults. This study examined the acute behavioral effects of oral diazepam and d-amphetamine in young adults, ages 18-21 years, who had consistently scored in the highest or lowest third of their grade-based cohort on a modified Sensation Seeking Scale that was completed annually between ages 10 and 14 years. Healthy participants completed 16 7.5-h test days, with test days separated by a minimum of 48 h. Each day, assessments consisting of computer task performance, verbal report of drug effects, and cardiovascular measures were completed 0, 50, 110, 170, 230, and 290 min after drug administration. Placebo and three active doses of diazepam and d-amphetamine (2.5, 5.0 and 10.0 mg/70 kg) were tested under double-blind conditions according to a randomized-block design. Typical stimulant and sedative effects were obtained with d-amphetamine and diazepam, respectively. Drug effects varied as a function of sensation-seeking status, with magnitude of effects on cardiovascular function, task performance, and report of positive drug effects being greater among high sensation seekers, and report of negative drug effects being greater among low sensation seekers. Adolescents who report high levels of sensation seeking on a consistent basis are more sensitive to pharmacological effects of stimulant and sedative drugs that are associated with abuse potential as young adults.

Medication errors are among the most common causes of unintended harm to patients and have led to many deaths. Some categories of medication errors include; medications administered to the wrong person; medications administered at the wrong time, through the wrong route; administration of the wrong medication and/or dose; and the omission of medications. Guided by the logic model, the just culture model, and the Knowles theory of andragogy, the purpose of the project was to determine if providing information related to evidence-based strategies to reduce medication errors would result in safer medication administration practices and improved patient outcomes A survey was administered to 11 medical and nursing staff at an outpatient internal medical clinic to determine their knowledge about medications errors prior to providing evidence-based information on strategies to reduce medication errors. After the educational session, a survey was conducted to determine staff members' retention of knowledge. A significant increase in the percent of correct responses to the survey from 68% to 100% after the educational session (t = -3.9; p = 0.001)) shows that the educational in-service had a positive outcome in increasing staff members' knowledge about reducing medication errors in an out-patient internal medicine clinic. Improving clinic staff knowledge and behaviors regarding medication administration has the potential to bring about social change by decreasing medication errors, improving patient safety, and improving health outcomes.

INTRODUÇÃO: Apesar da importância dos medicamentos antidepressivos no tratamento dos transtornos de humor e de ansiedade, sua ação sobre sistemas cerebrais responsáveis pela expressão emocional ainda não foram claramente estabelecidos. Estudos recentes têm examinando o sinal dependente de nível de oxigenação sanguínea (do inglês, \"BOLD\") durante estímulos emocionais em indivíduos saudáveis sob uso de antidepressivos. Nesse estudo, pretendemos estender essa avaliação às alterações do humor e comportamento emocional devido ao uso prolongado de um antidepressivo bloqueador de serotonina e noradrenalina em pessoas saudáveis. MÉTODOS: foram selecionados dezesseis voluntários, sem antecedentes psiquiátricos pessoais ou familiares, que participaram de um ensaio farmacológico simples-cego de quatro semanas de doses baixas de clomipramina (até 40 mg/dia). Ao final desse período, dez sujeitos foram selecionados como não responsivos, e os restantes seis sujeitos foram selecionados como responsivos por apresentarem claras mudanças em três dos quatro seguintes critérios: tolerância interpessoal, eficiência, bem estar, e mudança substancial em sua auto percepção. O grupo de sujeitos classificados como responsivos foram submetidos a um ensaio controlado duplo-cego confirmatório. A aquisição de imagens cerebrais ocorreu após quatro semanas de uso de medicação (simples cego) e quatro semanas após a sua suspensão, ao final da participação no ensaio farmacológico. O imageamento cerebral foi realizado durante a indução de estados afetivos de felicidade, irritabilidade e neutros por relatos autobiográficos. A resposta emocional desses estados foi obtida por escalas de auto avaliação de ansiedade, irritabilidade e felicidade. As diferenças de sinal entre os estados afetivos foram utilizadas para a análise estatística da interação dos efeitos estado medicamentoso e grupo por testes ANOVA. RESULTADOS: Foi encontrada uma interação significativa entre o efeito de grupo e o estado medicamentoso sobre os estados afetivos de irritabilidade, mas não sobre os de felicidade. Se observou redução na auto avaliação de ansiedade no grupo responsivo com o uso de medicação na diferença entre os estados induzidos de irritabilidade e felicidade, em comparação com o efeito no grupo não responsivo; e também, redução na auto avaliação de felicidade com o uso de clomipramina na totalidade da amostra, na diferença entre o estados induzidos de irritabilidade e neutro. A alteração sobre o efeito BOLD (p < 0,005) foi localizada em regiões adjacentes à junção frontoparietal para a indução de irritabilidade em relação à felicidade e em relação aos estados neutros, no grupo responsivo em relação ao não responsivo, durante o período em uso relativo àquele sem uso de clomipramina, e na junção têmporo-paríeto-occipital, exclusivamente para a diferença irritabilidade-felicidade. CONCLUSÕES: a modificação favorável que sujeitos saudáveis apresentaram ao uso prolongado de um antidepressivo bloqueador da serotonina e noradrenalina, pode estar relacionada à modificação no processamento cerebral da memória autobiográfica de emoções negativas / INTRODUCTION: despite the importance of antidepressant agents to the treatment of anxiety and depressive disorders, there is not yet a clear understanding of their actions upon specific brain systems relevant to emotional processing. Recent studies have examined blood oxygen level dependent (BOLD) signal during emotion stimuli in healthy individuals in antidepressant use. The study intends to extend these measures to the changes over mood and emotional behavior by prolonged use of a serotonin and noradrenaline blocker antidepressant. METHODS: we selected sixteen subjects, with no personal or family history of psychiatric disorders, which participated of a four-week single-blind trial with low doses of clomipramine (up to 40mg/day). After this period, ten subjects were classified as non responsives, the remaining six subjects being classified as responsives because clomipramine provided positive changes in three of four of the following criteria: interpersonal tolerance, self-efficacy, mood and self-perception of a substantial change. Responsives were included in a placebo-controlled confirmatory trial. Imaging sessions occurred at the end of the four-week course of clomipramine and again after a four-week clomipramine washout period, at the end of pharmacological trial. Subjects were scanned during the induction of irritability, happiness and neutral affective states by autobiographical recall. Self-report assessment was performed for each induction by anxiety, irritability and happiness scales. Inter-condition differences (affective induction) were used in the analysis of interaction of medication status and group effects by ANOVA tests. RESULTS: A significant interaction was found between group and treatment during irritability, but not during happiness emotions. It was observed a reduction in the scale of self-evaluation of anxiety in responsive group with the use of medication to the difference between irritability-happiness states, compared to the non responsive group; and a reduction in auto evaluation of happiness, in the totality of the sample in use of clomipramine, in difference irritability-neutral. There was a significant increase of BOLD effect in the responsive group during use relative to the period without use of clomipramine, compared to the effect on non-responsive group (p < 0.005). This effect was located in regions that surround the frontoparietal junction to the irritability relative to happiness and to irritability relative to neutral induction, and in the temporo-parieto-occipital junction, exclusively to the irritability relative to happiness induction. CONCLUSIONS: The favorably changes in healthy subjects who respond to prolonged serotonin and noradrenaline blocker use, may relate to changes in neural processes of autobiographical memory of negative emotions

INTRODUÇÃO: Apesar da importância dos medicamentos antidepressivos no tratamento dos transtornos de humor e de ansiedade, sua ação sobre sistemas cerebrais responsáveis pela expressão emocional ainda não foram claramente estabelecidos. Estudos recentes têm examinando o sinal dependente de nível de oxigenação sanguínea (do inglês, \"BOLD\") durante estímulos emocionais em indivíduos saudáveis sob uso de antidepressivos. Nesse estudo, pretendemos estender essa avaliação às alterações do humor e comportamento emocional devido ao uso prolongado de um antidepressivo bloqueador de serotonina e noradrenalina em pessoas saudáveis. MÉTODOS: foram selecionados dezesseis voluntários, sem antecedentes psiquiátricos pessoais ou familiares, que participaram de um ensaio farmacológico simples-cego de quatro semanas de doses baixas de clomipramina (até 40 mg/dia). Ao final desse período, dez sujeitos foram selecionados como não responsivos, e os restantes seis sujeitos foram selecionados como responsivos por apresentarem claras mudanças em três dos quatro seguintes critérios: tolerância interpessoal, eficiência, bem estar, e mudança substancial em sua auto percepção. O grupo de sujeitos classificados como responsivos foram submetidos a um ensaio controlado duplo-cego confirmatório. A aquisição de imagens cerebrais ocorreu após quatro semanas de uso de medicação (simples cego) e quatro semanas após a sua suspensão, ao final da participação no ensaio farmacológico. O imageamento cerebral foi realizado durante a indução de estados afetivos de felicidade, irritabilidade e neutros por relatos autobiográficos. A resposta emocional desses estados foi obtida por escalas de auto avaliação de ansiedade, irritabilidade e felicidade. As diferenças de sinal entre os estados afetivos foram utilizadas para a análise estatística da interação dos efeitos estado medicamentoso e grupo por testes ANOVA. RESULTADOS: Foi encontrada uma interação significativa entre o efeito de grupo e o estado medicamentoso sobre os estados afetivos de irritabilidade, mas não sobre os de felicidade. Se observou redução na auto avaliação de ansiedade no grupo responsivo com o uso de medicação na diferença entre os estados induzidos de irritabilidade e felicidade, em comparação com o efeito no grupo não responsivo; e também, redução na auto avaliação de felicidade com o uso de clomipramina na totalidade da amostra, na diferença entre o estados induzidos de irritabilidade e neutro. A alteração sobre o efeito BOLD (p < 0,005) foi localizada em regiões adjacentes à junção frontoparietal para a indução de irritabilidade em relação à felicidade e em relação aos estados neutros, no grupo responsivo em relação ao não responsivo, durante o período em uso relativo àquele sem uso de clomipramina, e na junção têmporo-paríeto-occipital, exclusivamente para a diferença irritabilidade-felicidade. CONCLUSÕES: a modificação favorável que sujeitos saudáveis apresentaram ao uso prolongado de um antidepressivo bloqueador da serotonina e noradrenalina, pode estar relacionada à modificação no processamento cerebral da memória autobiográfica de emoções negativas / INTRODUCTION: despite the importance of antidepressant agents to the treatment of anxiety and depressive disorders, there is not yet a clear understanding of their actions upon specific brain systems relevant to emotional processing. Recent studies have examined blood oxygen level dependent (BOLD) signal during emotion stimuli in healthy individuals in antidepressant use. The study intends to extend these measures to the changes over mood and emotional behavior by prolonged use of a serotonin and noradrenaline blocker antidepressant. METHODS: we selected sixteen subjects, with no personal or family history of psychiatric disorders, which participated of a four-week single-blind trial with low doses of clomipramine (up to 40mg/day). After this period, ten subjects were classified as non responsives, the remaining six subjects being classified as responsives because clomipramine provided positive changes in three of four of the following criteria: interpersonal tolerance, self-efficacy, mood and self-perception of a substantial change. Responsives were included in a placebo-controlled confirmatory trial. Imaging sessions occurred at the end of the four-week course of clomipramine and again after a four-week clomipramine washout period, at the end of pharmacological trial. Subjects were scanned during the induction of irritability, happiness and neutral affective states by autobiographical recall. Self-report assessment was performed for each induction by anxiety, irritability and happiness scales. Inter-condition differences (affective induction) were used in the analysis of interaction of medication status and group effects by ANOVA tests. RESULTS: A significant interaction was found between group and treatment during irritability, but not during happiness emotions. It was observed a reduction in the scale of self-evaluation of anxiety in responsive group with the use of medication to the difference between irritability-happiness states, compared to the non responsive group; and a reduction in auto evaluation of happiness, in the totality of the sample in use of clomipramine, in difference irritability-neutral. There was a significant increase of BOLD effect in the responsive group during use relative to the period without use of clomipramine, compared to the effect on non-responsive group (p < 0.005). This effect was located in regions that surround the frontoparietal junction to the irritability relative to happiness and to irritability relative to neutral induction, and in the temporo-parieto-occipital junction, exclusively to the irritability relative to happiness induction. CONCLUSIONS: The favorably changes in healthy subjects who respond to prolonged serotonin and noradrenaline blocker use, may relate to changes in neural processes of autobiographical memory of negative emotions

<p>In drug development clinical trials are designed to investigate whether a new treatment is safe and has the desired effect on the disease in the target patient population. Categorical endpoints, for example different ranking scales or grading of adverse events, are commonly used to measure effects in the trials. </p><p>Pharmacokinetic/Pharmacodynamic (PK/PD) models are used to describe the plasma concentration of a drug over time and its relationship to the effect studied. The models are utilized both in drug development and in discussions with drug regulating authorities. Methods for incorporation of ordered categorical data in PK/PD models were studied using a non-linear mixed effects modelling approach as implemented in the software NONMEM. The traditionally used proportional odds model was used for analysis of a 6-grade sedation scale in acute stroke patients and for analysis of a T-cell receptor expression in patients with Multiple Sclerosis, where the results also were compared with an analysis of the data on a continuous scale. Modifications of the proportional odds model were developed to enable analysis of a spontaneously reported side-effect and to analyze situations where the scale used is heterogeneous or where the drug affects the different scores in the scale in a non-proportional way. The new models were compared with the proportional odds model and were shown to give better predictive performances in the analyzed situations. </p><p>The results in this thesis show that categorical data obtained in clinical trials with different design and different categorical endpoints successfully can be incorporated in PK/PD models. The models developed can also be applied to analyses of other ordered categorical scales than those presented.</p>

In drug development clinical trials are designed to investigate whether a new treatment is safe and has the desired effect on the disease in the target patient population. Categorical endpoints, for example different ranking scales or grading of adverse events, are commonly used to measure effects in the trials. Pharmacokinetic/Pharmacodynamic (PK/PD) models are used to describe the plasma concentration of a drug over time and its relationship to the effect studied. The models are utilized both in drug development and in discussions with drug regulating authorities. Methods for incorporation of ordered categorical data in PK/PD models were studied using a non-linear mixed effects modelling approach as implemented in the software NONMEM. The traditionally used proportional odds model was used for analysis of a 6-grade sedation scale in acute stroke patients and for analysis of a T-cell receptor expression in patients with Multiple Sclerosis, where the results also were compared with an analysis of the data on a continuous scale. Modifications of the proportional odds model were developed to enable analysis of a spontaneously reported side-effect and to analyze situations where the scale used is heterogeneous or where the drug affects the different scores in the scale in a non-proportional way. The new models were compared with the proportional odds model and were shown to give better predictive performances in the analyzed situations. The results in this thesis show that categorical data obtained in clinical trials with different design and different categorical endpoints successfully can be incorporated in PK/PD models. The models developed can also be applied to analyses of other ordered categorical scales than those presented.