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Zeineddine, Maya. "Sécurité et Efficacité à Long Terme des Thérapies Modificatrices de la Maladie à Haute Efficacité chez les Patients Atteints de Sclérose en Plaques". Electronic Thesis or Diss., Limoges, 2024. http://www.theses.fr/2024LIMO0082.
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La sclérose en plaques (SEP) est une maladie inflammatoire chronique du système nerveux central, entraînant une invalidité significative chez les personnes atteintes. Le paysage thérapeutique de la SEP a évolué au cours des dernières décennies, avec l'introduction de diverses thérapies modificatrices de la maladie (TMM) à haute efficacité. Cette thèse examine la sécurité et l'efficacité à long terme de ces thérapies, en particulier dans le contexte de la région du Moyen-Orient et de l'Afrique du Nord (MENA). La recherche comprend une analyse approfondie de l'accessibilité aux traitements, des obstacles à la thérapie, et des résultats cliniques des patients atteints de SEP dans cette région. Elle inclut cinq études explorant la disponibilité et l'accessibilité des TMM, l'impact de la pandémie de COVID-19 sur la gestion de la SEP, et la comparaison du natalizumab avec les anticorps monoclonaux anti-CD20. Les résultats soulignent des disparités significatives dans l'accès aux traitements et la nécessité de stratégies régionales ciblées pour améliorer la prise en charge de la SEP. De plus, la recherche contribue à la compréhension mondiale de la SEP en fournissant des informations sur les résultats à long terme des TMM à haute efficacité dans un contexte réelMultiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system, leading to significant disability among affected individuals. The treatment landscape for MS has evolved over the past decades, with the introduction of various high-efficacy disease-modifying therapies (DMTs). This thesis investigates the long-term safety and efficacy of these therapies, particularly in the context of the Middle East and North Africa (MENA) region. The research involves a comprehensive analysis of treatment accessibility, barriers to therapy, and the clinical outcomes of MS patients in this region. It includes five studies that explore the availability and accessibility of DMTs, the impact of the COVID-19 pandemic on MS management, and the comparison of natalizumab with anti-CD20 monoclonal antibodies. The findings underscore significant disparities in treatment access and the need for targeted regional strategies to improve MS management. Furthermore, the research contributes to the global understanding of MS by providing insights into the long-term outcomes of high-efficacy DMTs in a real-world setting
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Burgess, John Robert Martin E. Davis. "Efficacy of long-term and short-term residential substance abuse treatment modalities". Auburn, Ala., 2005. http://repo.lib.auburn.edu/2005%20Fall/Thesis/BURGESS_JOHN_18.pdf.
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McClure, Crystal. "Strategies for Increasing Self-Efficacy in Long-Term Welfare Recipients". ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7824.
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With the imposition of lifetime limitations on an individual's ability to receive cash assistance, there is a group of long-term Temporary Assistance for Needy Families (TANF) recipients that have approached the lifetime limitation without becoming gainfully employed. Many long term TANF recipients report low levels of self-efficacy which inhibits their ability to successfully transition off welfare and into the workforce. However, most welfare-to-work programs do not address the emotional or psychological well-being of their clients, instead they focus on job placement and job readiness skills. The purpose of this sequential–exploratory mixed methods study is to identify the primary barriers to employment that have a negative effect on long term TANF recipient's self-efficacy. Albert Bandura's self-efficacy theory was the theoretical foundation for this study. Semi structured interviews with 20 long term TANF recipients helped answer the central research questions regarding barrier identification. The participants agreed that support for completing GED, as well as a more holistic approach to addressing their barriers is most effective in helping them transition off welfare and into the workforce. Hong's Employment Hope Scale (EHS-14) was used to collect the quantitative data for this study. The quantitative data were analyzed by multiple regression analysis and found that level of education has a statistically significant moderating effect on length of time on welfare and level of self-efficacy. This study may inform welfare-to-work providers and programmers on the importance of addressing TANF recipients' psychological needs, such as low self-efficacy before attempting to transition them into the workforce.
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Bulbulia, Richard. "Long term follow-up of the MRC/BHF Heart Protection Study : the assessment during a six year post-trial period of the effects of five years lipid-lowering therapy with simvastatin 40 mg daily and separately, antioxidant vitamin supplementation with 600 mg vitamin E, 250 mg vitamin C and 20 mg β-carotene in 17,519 surviving Heart Protection Study participants". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609948.
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Stotland, Stephen Charles. "Dieting self-efficacy : its relation to situational and long-term dieting success". Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75893.
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Questionnaires were constructed to measure dieter's beliefs in their abilities to (1) adhere to a diet in eating situations, (2) perform various dieting behaviors, and (3) reach their dieting goals. The three questionnaires were called the Situation-, Behavior-, and Goal-Based Dieting Self-Efficacy Scales.Preliminary work examined the reliability of the three scales. The Situtation-Based scale demonstrated a high level of test-retest reliability over a two to four week period in the two college samples. Examination of scale intercorrelations in the clinical sample indicated that the scales were correlated at only a low level, suggesting that the scales measure different aspects of the construct of dieting self-efficacy.
Results of the laboratory studies demonstrated that the Situation-Based scale was a significant predictor of how much dieters ate in response to two different types of challenges to their diets, high calorie preloads and a depressed mood induction.
The ability of the three scales to predict weight changes was examined in the clinical sample. Only the Goal-Based scale was found to predict weight change.
In summary, the present study adds to the body of literature supporting goal-based dieting self-efficacy as a significant predictor of weight change during dieting attempts. Suggestions were offered about ways to apply this finding to clinical practice, in the areas of patient selection and treatment prescription.
The present research was limited in the following ways. The laboratory studies were limited by the narrow range of subjects, and the artificiality of the eating situation. Future research should extend this finding with other populations, as well as methodologies for examining the relation between dieting self-efficacy and eating in real-life situations. The clinical study was limited by the absence of a follow-up assessment. Future research must examine the ability of dieting self-efficacy to predict weight change over longer periods of time. Finally, suggestions were made concerning the importance of future research attempting to clarify the construct of dieting self-efficacy, particularly research aimed at determining the relation between responses to these questionnaires and the actual cognitive processes engaged in by dieters in eating situations, and over the course of their weight control efforts. (Abstract shortened with permission of author.)
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Berish, Diane E. "INVESTIGATING THE EFFICACY OF SKILLED-NURSING FACILITIES’ TRANSITIONAL CARE PROGRAMS ON REDUCING 30-DAY HOSPITAL READMISSIONS". Miami University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=miami1531907403994485.
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Alsfouk, Bshra Ali A. "Long-term efficacy and tolerability of antiepileptic drugs in newly diagnosed epilepsy patients". Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/9104/.
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Epilepsy is the most common serious chronic neurological disorder, affecting 65 million people worldwide. Antiepileptic drugs (AEDs) constitute the main treatment for epilepsy. The introduction of 14 new AEDs over the last three decades has expanded treatment options and increased the expectations about efficacy and tolerability. However, little is known about the effectiveness of new AEDs in routine clinical practice. It is also unclear whether the treatment outcomes in epilepsy have improved in recent decades as a consequence of the availability of an increasing number of AEDs. The present work attempts to provide a comprehensive evaluation of efficacy, tolerability, and retention rate of AED treatments in everyday clinical setting. This thesis is divided into six chapters, three general chapters and three result chapters (Chapter 3, 4, and 5). Chapter 1 sorts out the background of epilepsy, pharmacological management, and adverse drug reactions. The new classification of seizures and epilepsies, AED therapy, and guidelines for initiation, selection and dosing of AEDs are described. Followed by discussion of clinically relevant adverse effects of AEDs. Chapter 2 describes the study population and definition of outcome measures. Data collection and statistical analysis were presented as well. The data of this study were extracted retrospectively by reviewing the patients’ medical records. The patients were first diagnosed with epilepsy and prescribed AED treatment at the Glasgow Epilepsy Unit between Jul 1982 and Oct 2012; then they were prospectively followed up until 30 Apr 2016 with at least one year follow-up after starting AEDs therapy. The study cohort included 1,528 patients aged 18 to 93 years (median 37), 849 (56%) were men, and 1,290 (84%) had focal epilepsy. Chapter 3 evaluates efficacy of AEDs and the changes in treatment outcomes of epilepsy over the past 30 years. This was achieved by comparing the results of current analysis to the results of three analyses conducted in 1999, 2003, and 2008 on same expanding cohort (n=470, 890, and 1,098 respectively) from the Epilepsy Unit in Glasgow. The overall efficacy rate of AEDs in this study was 62% (n=941/1,528); this was comparable to what was observed in the previous analysis of 17 years ago on the same expanding cohort in which 64% (n=301/470) of newly diagnosed epilepsy patients achieved seizure-free. Likewise, the efficacy rates of different established and new AEDs were comparable. Therefore, this provides a strong evidence that treatment outcomes in epilepsy have not improved in recent decades despite the availability of increasing number of AEDs. However, the results indicated that the use of new AEDs has increased, 41% of patients continued to take the new AEDs as a monotherapy in the current study, compared to 26% in 1999. This most likely due to their advantages in terms of tolerability. This analysis also found that family history of epilepsy, more than ten pre-treatment seizures, psychiatric conditions, alcohol and recreational drugs abuse, and failure to response to two or more AEDs were significantly associated with poor seizure outcomes. In Chapter 4, the rate and predictors of intolerable adverse effects of AEDs were assessed. This study showed that 28% (n=815/2,911) of total AEDs prescriptions were discontinued because of poor tolerability. In which the most frequent problem was tiredness (5.2%, n=152/2,911) followed by poor coordination and rash, with a 2.9% (n=86) incidence for each. Among 17 different AEDs, lamotrigine was associated with the best tolerability whether it was used as monotherapy (19%, n=109/575) or as part of polytherapy (9%, n=35/387). While topiramate was associated with the highest rate of adverse effects (39%, n=32/81) among monotherapies, and retigabine had the highest rate of adverse effects (42%, n=8/19) among AEDs used as part of polytherapy. Moreover, each AED demonstrated a distinct tolerability profile; the main intolerable adverse reaction associated with lamotrigine and carbamazepine was skin rash while valproate was poorly tolerated most frequently due to tremor and weight gain. Furthermore, levetiracetam was poorly tolerated commonly due to psychiatric and behavioural side effects whereas cognitive dysfunction was the most common reason for topiramate intolerability. Beside individual AED, poor tolerability was related to patient’s susceptibility and number of co-prescribed AEDs. Prior intolerable AEDs schedule was associated with high probability to experience intolerable adverse effects at subsequent AED schedule. Likewise, female, focal epilepsy, more than ten pre-treatment seizures, and psychiatric comorbidity were significantly associated with higher rates of adverse effects. However, older AEDs usage was not significantly associated with poorer tolerability. These may present novel findings from this study as very few studies have evaluated the predictors for poor tolerability particularly non-AEDs variables. In Chapter 5, a survival analysis was performed to identify retention rates (time to discontinuation) of lamotrigine, valproate, carbamazepine, and levetiracetam monotherapies. Lamotrigine showed the highest retention rate, with median duration of therapy of 84 months. This was significantly higher than the retention times of valproate (42 months), carbamazepine (36 months), and levetiracetam (36 months); there was no significant difference in retention rates of other AEDs. However, within six months of therapy initiation, lamotrigine and carbamazepine demonstrated the highest discontinuation rates, most probably due to rash. Few observational studies have investigated the long-term retention rates of AEDs in the UK. Therefore, the current research may present novel findings in term of population as well. In Chapter 6, study strengths and limitations are presented. Clinical implications and the future directions of research in epilepsy are described as well.
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Kent, Lisa. "Practicing Self-Efficacy and Transparency to Achieve Long-Term Recovery and Reduce Recidivism". ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/7397.
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There is limited data about the positive application of self-efficacy and the practice of transparency for individuals in recovery to achieve long-term recovery from substance addiction and criminal recidivism. The purpose of this qualitative phenomenological study was to gain more insight and knowledge about how the application of self-efficacy and the practice of transparency help individuals in recovery achieve long-term recovery from substance addiction and criminal recidivism for two or more years. The conceptual framework used to guide this study was Albert Bandura's self-efficacy theory. This study is significant because it explains that long-term recovery is not an easy task to achieve, and many individuals who have a history of addiction and criminal behavior find it extremely difficult to achieve long-term recovery. A qualitative phenomenological approach was used for this study. This study employed a chain sample, using a semi-structured interview guide composed of open-ended questions. Five individuals agreed to the study and reported applying and practicing self-efficacy and transparency to achieve long-term recovery. The study analyzed and coded data to identify categories and themes. The findings reveled the importance of the use of self-efficacy and transparency in achieving long-term recovery from substances and decreasing recidivism. Themes identified was the ability to live day-to-day, breaking the cycle of addiction and recidivism, believing they are worth recovery (a better life), and sharing their story (transparency). This study may stimulate positive social change with the application of self-efficacy, as people struggling with addiction and recidivism may learn the importance of being transparent during the recovery process.
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Woensel, Jacobus Bernardus Maria van. "Lower respiratory tract infection caused by respiratory syncytial virus the short-term and long-term efficacy of corticosteroids /". [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/63898.
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Kotrappa, Neel. "The Efficacy of Long-Term Kinesio Tape on Grip Strength in a Healthy Population". Scholarship @ Claremont, 2014. http://scholarship.claremont.edu/cmc_theses/976.
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Kinesio® Tape was invented in 1973, and since has been used in various clinical and therapy settings to prevent and heal a multitude of physical conditions. Kinesio® Tape is a 100% cotton-based elastic tape that when applied to the skin pulls the skin upwards and creates more space by lifting the fascia and soft tissue, thus increasing blood flow and decreasing edema. The tape was also purported to facilitate the strengthening of weakened muscles through neuromuscular facilitation. The objective behind this study was to determine the long-term effects of applied forearm Kinesio® Tape on maximal grip strength when paired with an exercise program. The study took place at the CMS Athletic Training Center, and was designed to be a matched-pairs, single group, repeated measures experiment. Thirty- two healthy members of the Claremont College community voluntarily participated in this study. There was 16 male and 16 female participants (average age: 21.46 ± 1.76 years; average height 174.92 ± 9.40 cm; average body weight 69.17 ± 9.20 kg). The maximal grip strength of both the dominant and non-dominant hands was measured using a JAMAR Hydraulic Hand Dynamometer. Each of the 32 subjects also participated in an exercise program for two weeks and provided a grip strength measurement at the end of each week. Maximal grip strength values were assessed using a standard paired-samples t-test. Results revealed a significant difference in grip strength in the dominant arm (exercise with Kinesio® Tape) compared to the non-dominant arm (exercise only). When combined with a relatively low to medium level exercise program, Kinesio® Tape significantly increased grip strength when compared to an exercise program alone in a healthy population.
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Campbell, Elizabeth M. "Efficacy of Long-Term Use of Vocal Cool Downs as Analyzed through Aerodynamic Measurements". Miami University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=miami1430424728.
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Meurer, Michael, Manige Fartasch, Gisela Albrecht, Thomas Vogt, Margitta Worm, Thomas Ruzicka, Peter Josef Altmeyer, Dirk Schneider, Gottfried Weidinger y Matthias Bräutigam. "Long-Term Efficacy and Safety of Pimecrolimus Cream 1% in Adults with Moderate Atopic Dermatitis". Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-135560.
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Background: Pimecrolimus cream 1% is a non-steroid, selective inflammatory cytokine inhibitor indicated for atopic dermatitis (AD). Objective: To compare the safety and efficacy of pimecrolimus cream 1%-based treatment versus conventional therapy in adults with moderate AD. Methods: Patients were randomized to receive pimecrolimus cream 1% (n = 62) or vehicle (n = 68) at the first signs/symptoms of AD, for 24 weeks as required. A moderately potent topical corticosteroid (prednicarbate 0.25% cream) was allowed in both groups to treat flares. Results: Corticosteroids were required on fewer days in the pimecrolimus group, compared with the vehicle group (9.7 vs. 37.8%, p < 0.001). Furthermore, 59.7% of pimecrolimus-treated patients experienced no flares during the study period, compared with 22.1% of vehicle-treated patients (p < 0.001). Pimecrolimus cream 1% was well tolerated throughout the study. Conclusion: For adults with moderate AD, pimecrolimus cream 1% is well tolerated, reduces the incidence of flares, reduces/eliminates corticosteroid use, improves long-term disease control and enhances the patients’ quality of lifeDieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Meurer, Michael, Manige Fartasch, Gisela Albrecht, Thomas Vogt, Margitta Worm, Thomas Ruzicka, Peter Josef Altmeyer, Dirk Schneider, Gottfried Weidinger y Matthias Bräutigam. "Long-Term Efficacy and Safety of Pimecrolimus Cream 1% in Adults with Moderate Atopic Dermatitis". Karger, 2004. https://tud.qucosa.de/id/qucosa%3A27660.
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Background: Pimecrolimus cream 1% is a non-steroid, selective inflammatory cytokine inhibitor indicated for atopic dermatitis (AD). Objective: To compare the safety and efficacy of pimecrolimus cream 1%-based treatment versus conventional therapy in adults with moderate AD. Methods: Patients were randomized to receive pimecrolimus cream 1% (n = 62) or vehicle (n = 68) at the first signs/symptoms of AD, for 24 weeks as required. A moderately potent topical corticosteroid (prednicarbate 0.25% cream) was allowed in both groups to treat flares. Results: Corticosteroids were required on fewer days in the pimecrolimus group, compared with the vehicle group (9.7 vs. 37.8%, p < 0.001). Furthermore, 59.7% of pimecrolimus-treated patients experienced no flares during the study period, compared with 22.1% of vehicle-treated patients (p < 0.001). Pimecrolimus cream 1% was well tolerated throughout the study. Conclusion: For adults with moderate AD, pimecrolimus cream 1% is well tolerated, reduces the incidence of flares, reduces/eliminates corticosteroid use, improves long-term disease control and enhances the patients’ quality of life.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Leung, Chun Chuen. "Study of long-term efficacy of electroacupuncture for chronic neck pain : a randomized controlled trial". HKBU Institutional Repository, 2012. https://repository.hkbu.edu.hk/etd_ra/1440.
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Rocha, Joana Raquel Martins. "A eficácia a longo prazo dos antidepressivos na depressão: revisão sistemática". Master's thesis, Universidade Portucalense, 2014. http://hdl.handle.net/11328/1065.
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Dissertação de Mestrado em Psicologia Clínica e da Saúde.Objetivo: Avaliar a eficácia de longo prazo dos antidepressivos no tratamento da perturbação depressiva major e/ou perturbação distímica. Métodos de Pesquisa: Realização de pesquisa eletrónica via EBSCO nas seguintes bases de dados com restrição de língua: Academic Search Complete; CINAHL Plus; MedicLatina; MedLine; PsycArticles; Psychology and Behavioral Sciences Collection; PsycINFO; SocINDEX; e SportDiscus. Critérios de Seleção: Todos os estudos randomizados e com grupo de controlo (RCTs) de período igual ou superior a um ano após a randomização, entre antidepressivos versus placebo, em pacientes diagnosticados com perturbação depressiva major e/ou perturbação distímica, na ausência de episódios de mania e/ou hipomania e outras comorbilidades. Recolha e Análise dos Dados: Os estudos incluídos foram inspecionados por dois autores. Foi avaliada a qualidade metodológica do risco de viés de diferentes parâmetros do estudo, tendo por base as diretrizes da Cochrane Collaboration. Os resultados avaliados foram: mortalidade, estado global, estado mental e efeitos secundários. Resultados: Num total de 4225 resultados obtidos, 10 preencheram os critérios de inclusão. Todos os estudos demonstraram a capacidade de prevenção de recaídas/recorrências dos antidepressivos, quando comparados com o placebo. A diferença da taxa média entre antidepressivos versus placebo: por recaída/recorrência foi de 23%; por abandono do tratamento por outras razões que não por recaída/recorrência foi de 3%; e a proporção de participantes que não completaram o estudo foi de 24%. Todos os estudos incluídos apresentam lacunas metodológicas nos diferentes parâmetros analisados (e.g. inclusão apenas dos participantes que manifestaram benefício clínico do tratamento antidepressivo, num momento antecedente ao estudo; presença de conflito de interesses). Conclusão: Perante os resultados obtidos na atual revisão, considera-se que ainda não existem evidências claras e confiáveis sobre a eficácia a longo prazo do tratamento antidepressivo na depressão.
Aims: To evaluate the long-term efficacy of antidepressants in the treatment of major depressive disorder and/or dysthymic disorder. Search Methods: Conducting electronic survey via the following EBSCO databases with constraint language: Academic Search Complete; CINAHL Plus; MedicLatina; MedLine; PsycArticles; Psychology and Behavioral Sciences Collection; PsycINFO; SocINDEX; and SportDiscus. Selection Criteria: All randomized studies with control group (RCTs) of period equal to or more than 1 year after randomization between antidepressants versus placebo in patients with major depressive disorder and/or dysthymic disorder, in the absence of episodes of mania and/or hypomania and other comorbidities. Collection and Analysis Data: The included studies were inspected by two authors. It was assessed the methodological quality of the risk of bias of different parameters of the study, based on the guidelines of the Cochrane Collaboration. The results assessed were: mortality, global state, mental state, and side effects. Main Results: A total of 4225 results, 10 met the inclusion criteria. All studies demonstrated the ability to prevent relapse/recurrence of antidepressants compared to placebo. The average rate of the difference between antidepressants versus placebo: by relapse/recurrence was 23%; by dropout treatment for other reasons than a relapse/recurrence was 3%; and the proportion of participants who did not complete the study was 24%. All the included studies show methodological weaknesses in the differents the parameters analyzed (e.g. including only participants who expressed clinical benefit of antidepressant treatment, a time preceding the study; presence of conflict of interest). Conclusion: Given the results obtained in the current revision, it is considered that there are still no clear and reliable evidence about the long-term efficacy of antidepressant treatment in depression.
Orientação: Professor Doutor Gil Nata.
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Baer, Shannon L. "Efficacy of complementary and alternative medicine on perceived well-being in geriatric long-term care residents". [Denver, Colo.] : Regis University, 2008. http://165.236.235.140/lib/SBaer2008.pdf.
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Kehl, Kevin L. Cloud Robert C. "Differences in self-efficacy and global-mindedness between short-term and semester-long study abroad participants of selected Christian universities". Waco, Tex. : Baylor University, 2005. http://hdl.handle.net/2104/3013.
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Fredriksen, Lauren E. "The Impact of Memory Stereotype Threat on Memory and Memory Self-Efficacy in Older Adults". Xavier University Psychology / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=xupsy1593210266566016.
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Romaniuk, S. A., N. A. Opolonskaja y E. V. Kysenko. "Comparison of efficacy and safety of long-term warfarin therapy in patients with non-valvular atrial fibrillation". Thesis, Sumy State University, 2016. http://essuir.sumdu.edu.ua/handle/123456789/47871.
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Introduction: Anticoagulation with vitamin K antagonist (VKA) has been an enduring gold standard for stroke prevention in atrial fibrillation (AF). But the potential for serious bleeding complications of the drug remains a problem for the safe use of drug. Aim: Examine the prevalence of thromboembolic and bleeding complications in patients with non-valvular atrial fibrillation who receiving warfarin.
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Redondo, Pena Roger Lluis. "Tagging and capture hypothesis of synaptic plasticity : the roles of calmodulin kinases and the phenomenon of behavioural tagging". Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4421.
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The aims of this thesis were (1) to learn about the identities of the molecules involved in the maintenance of long-term potentiation (LTP), and (2) to develop and test a behavioural paradigm capable of elucidating the interaction between these molecular processes and the persistence of long-term memories. By improving the stability of field recordings in in vitro electrophysiology, it was possible to investigate the molecular processes that determine the long-term changes in synaptic efficacy. In these experiments, the interactions between two convergent inputs onto the same neuronal population in the CA1 region of the hippocampus were monitored for over ten hours. Analytically powerful three-pathway protocols using sequential strong and weak tetanization in varying orders, and test stimulation over long periods of time after LTP-induction, enabled a pharmacological dissociation of potentially distinct roles of the calmodulin kinase (CaMK) pathways in LTP. This places constraints on the mechanisms by which synaptic potentiation, and possibly memories, become stabilized. The experiments show that tag setting is blocked by the CaMK inhibitor KN-93 that, at low concentration primarily blocks CaMKII, whereas a CaMKK inhibitor, STO-609, selectively limits the synthesis or the availability of plasticity related proteins (PRPs). To test whether memories can be subject to modulation by independent experiences, behavioural studies tested the possibility of lengthening the persistence of a relatively weak memory by pairing its induction with an event capable of inducing the synthesis of the required PRPs. Corticosterone-dependent stressful events like a cold swim proved to interfere and weaken spatial memories. On the other hand, the exploration of a novel environment succeeded in rescuing the decay of a weak memory. The effect of the exploration of the novel environment was dependent on NMDA and dopamine receptor activation, as well as protein synthesis. These results are discussed in relation to the synaptic tagging and capture hypothesis and a novel model of the neuronal mechanisms underlying synaptic plasticity is developed from them.
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Chan, Raymond. "A long-term evaluation of the impact of rehabilitation in home (RIO) program on health outcomes in older adults". Thesis, Queensland University of Technology, 2008. https://eprints.qut.edu.au/16623/1/Raymond_Chan_Thesis.pdf.
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Background:
Older adults experience health deconditioning during hospitalization. There are many facets of care impacting on older adults' health characteristics and their self confidence in managing their health. The aim of this follow-up study is to examine the long term effect of comprehensive discharge planning and nursing in-home follow-up for older adults (over 65 year old) incorporating physiotherapy exercise strategies on health characteristics. No published studies were located that had examined the impact of a comprehensive discharge program on the functional status and psychosocial among older frail adults at 12 months post-discharge.
Design and methodology:
Rehabilitation in Older People (RIO program) is a randomised controlled trial which evaluates the intervention of a comprehensive discharge program, exercise program incorporating nursing follow up. Participants of the RIO study were randomly allocated into usual care control group and an intervention group. The intervention group received a comprehensive training from an advanced practice gerontic nurse (APGN) and exercise strategies by physiotherapists. The APGN visited the participants in their home 48 hours post discharge, followed by telephone follow-up at 4, 8, 12 and 24 weeks. This study followed-up this cohort at 12 month via telephone interviews to evaluate their functional ability, quality of life, psychosocial characteristics and the levels of self-efficacy. The General Self-efficacy Scale (GSE) was used to measure their self-efficacy.
Results:
There is no difference between the demographic and health characteristics between the control and intervention group. There are significant difference in their functional ability, psychosocial health, measured by the tools mentioned above at 4 weeks (p < 0.05), 12 weeks (p < 0.05), and 24 weeks (p < 0.05), but not at 52 weeks. The possible reason could be due to lack of telephone follow up. Moreover, the levels of self-efficacy in this sample have been found to correlate with the functional ability and psychosocial at 12 months after discharge from an acute hospital.
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Chan, Raymond. "A long-term evaluation of the impact of rehabilitation in home (RIO) program on health outcomes in older adults". Queensland University of Technology, 2008. http://eprints.qut.edu.au/16623/.
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Background: Older adults experience health deconditioning during hospitalization. There are many facets of care impacting on older adults' health characteristics and their self confidence in managing their health. The aim of this follow-up study is to examine the long term effect of comprehensive discharge planning and nursing in-home follow-up for older adults (over 65 year old) incorporating physiotherapy exercise strategies on health characteristics. No published studies were located that had examined the impact of a comprehensive discharge program on the functional status and psychosocial among older frail adults at 12 months post-discharge. Design and methodology: Rehabilitation in Older People (RIO program) is a randomised controlled trial which evaluates the intervention of a comprehensive discharge program, exercise program incorporating nursing follow up. Participants of the RIO study were randomly allocated into usual care control group and an intervention group. The intervention group received a comprehensive training from an advanced practice gerontic nurse (APGN) and exercise strategies by physiotherapists. The APGN visited the participants in their home 48 hours post discharge, followed by telephone follow-up at 4, 8, 12 and 24 weeks. This study followed-up this cohort at 12 month via telephone interviews to evaluate their functional ability, quality of life, psychosocial characteristics and the levels of self-efficacy. The General Self-efficacy Scale (GSE) was used to measure their self-efficacy. Results: There is no difference between the demographic and health characteristics between the control and intervention group. There are significant difference in their functional ability, psychosocial health, measured by the tools mentioned above at 4 weeks (p < 0.05), 12 weeks (p < 0.05), and 24 weeks (p < 0.05), but not at 52 weeks. The possible reason could be due to lack of telephone follow up. Moreover, the levels of self-efficacy in this sample have been found to correlate with the functional ability and psychosocial at 12 months after discharge from an acute hospital.
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Olotu, Ally Ibrahim. "Long term efficacy of a pre-erythrocytic malaria vaccine and correlates of protection in children residing in a malaria endemic country". Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:3fcbab1a-689a-41bd-8685-4762941f7b0c.
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Malaria remains an important cause of morbidity and mortality among children in sub-Saharan Africa despite recent reductions in malaria incidence in some parts of Africa. Current control tools face threats such as the emergence of drug resistant parasites and insecticide resistant mosquitoes. A malaria vaccine is needed to complement and/or replace existing tools in order to achieve better malaria control and eventually eliminate the disease. RTS,S/AS01E is the most clinically advanced pre-erythrocytic malaria vaccine candidate and is currently being tested in a phase III trial. The short-term efficacy of RTS,S/AS01E is known but the duration of protection is unknown. Furthermore, although RTS,S is protective, it is unclear which immunological assays predict efficacy: hence there are no known correlates of vaccine-induced protection against clinical malaria. In a randomized controlled trial, I assessed the efficacy of RTS,S/AS01E in children (5-17 months old) residing in Kilifi, Kenya, over 4 years of follow-up and determined the correlates of protection against clinical malaria. In order to examine the effect of variations in malaria exposure on vaccine efficacy, I developed an individual marker of malaria exposure calculated as distance-weighted prevalence of malaria infection within 1 km radius of every child. Over 4 years of follow-up, RTS,S/AS01E had an efficacy of 29.9% (95%CI: 10.3% to 45.3%, p=0.005) and 16.8% (95%CI: -8.6% to 36.3% p=0.18) against first and all malaria episodes, respectively (by intention to treat analysis). Vaccine efficacy waned over time and with increasing malaria exposure. RTS,S/AS01E efficacy was 43.6% (95% CI, 15.5 to 62.3) in the first year but was -0.4% (95% CI, -32.1 to 45.3) in the fourth year. Vaccine efficacy was 45.1% (95%CI 11.3% to 66.0%) among children with lower than average malaria exposure index, but 15.9% (95%CI -11.0 to 36.4%) among children with higher than average malaria exposure index. Despite waning in efficacy, RTS,S/AS01E averted 65 cases of malaria per 100 vaccinated children, with more cases averted among the children in the higher malaria-exposure cohort (78 cases per 100 vaccinated children) than those the low exposure cohort (62 cases per 100 vaccinated children). RTS,S/AS01E induced high titres of anti-CS protein antibodies and CD4+ T cell but not CD8+ T cell responses. Anti-CS antibody titres and the frequency of TNF-α producing CD4+ T cell responses were independently associated with protection from clinical malaria, and the combination of both anti-CS titers and TNF-α producing CD4+ T cell response satisfied the Prentice criteria for surrogate markers of protection. There was no association between avidity of RTS,S-induced anti-CS protein antibodies and protection from clinical malaria. Conclusions: RTS,S/AS01E efficacy against all episodes is 16.8% over the 4 years of follow-up. The vaccine efficacy wanes over time and with increasing malaria exposure. RTS,S/AS01E-induced TNF-α producing CD4 T cell and anti-CS protein antibody responses were independently associated with protection from clinical malaria. Anti-CS avidity did not predict protection from clinical malaria. Long-term follow-ups of malaria vaccine trials are essential in the evaluation of the longevity of vaccine efficacy.
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Norling, Jack y Jessica Unebrink. "Proaktiva och tidiga rehabiliteringsinsatser – En bortglömd möjlighet : En utvärderingsforskning av en rehabiliteringstjänst inom företagshälsovård". Thesis, Ersta Sköndal högskola, Institutionen för socialvetenskap, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:esh:diva-2376.
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Syftet med vår studie var att problematisera Susano AB:s tjänst Rehablinjen med hjälp av KASAM-teorins livsfrågeformulär som verktyg för att nå insikt om tjänsten hade potential för att i framtiden användas vid upprepad korttidsfrånvaro samt vid konflikter på arbetsplatsen. Syftet med tjänsten Rehablinjen ämnar identifiera bakomliggande faktorer till den upprepade korttidsfrånvaron eller konflikterna och på så sätt förebygga risk för långtidssjukskrivningar, vilket vi anser är en av dagens gedigna samhällsproblem. Studien hade två mätpunkter med fyra veckors mellanrum och genom dessa ämnade vi författare utläsa om Susano AB:s medarbetarenkät fångade upp de potentiella förändringarna som skett hos medarbetarna mellan mätpunkt ett och två, samt om minskningen eller ökningen av enkätens riskfaktorer låg i linje med den förändring som skett utifrån medarbetarens KASAM-värde. Vi ämnade även ta reda på medarbetarnas egen uppfattning om insatsens påverkan och om den upplevdes ha påverkat det fysiska och/eller psykiska välmåendet. Vi blev tilldelade en grupputredning av Susano AB som var för tiden av vår C-uppsats deras aktuella uppdragsgivare. Arbetsgruppen bestod av 15 anställda individer inom vård och omsorg i landstingsregi som alla var anställda på samma avdelning. Vi gjorde ett urval på tio av dessa varav vi senare fick ett bortfall på två medarbetare. Den slutliga undersökningsgruppen bestod av tre sjuksköterskor och fem skötare som haft en lång historia med konflikter och mobbing på sin arbetsplats. Forskningen består av en övergripande kvantitativ forskningsansats då studien har sin grund i två strukturerade enkäter – Susano AB:s medarbetarenkät och KASAM-enkäten – som vårt materialinsamlade inleddes med genom att medarbetarna fick besvara dem. Därefter följdes utfallet från Susano AB:s enkät upp med en kvalitativ och kompletterande intervju för att säkerställa att de riskfaktorer som enkäten visade på stämde väl överens med medarbetarens verklighet. Fyra veckor senare utfördes mätpunkt två som var upplagd på samma sätt för att uppmärksamma potentiella förändringar i medarbetarnas arbetssituation på avdelningen. Resultatet visade på att fem av studiens åtta medarbetare hade fått ett högre KASAM-värde vid mätpunkt två och att sju medarbetare hade fått ett minskat antal riskfaktorer fyra veckor efter tjänstens början och att en medarbetare hade samma antal riskfaktorer.
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Tinnin, Richard K. "The effectiveness of a long-term professional development program on teachers' self-efficacy, attitudes, skills, and knowledge using a thematic learning approach /". Digital version accessible at:, 2000. http://wwwlib.umi.com/cr/utexas/main.
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Peto, Thomas Julian. "Long-term efficacy and effectiveness of hepatitis B vaccination in The Gambia : Gambia Hepatitis Intervention Study (GHIS, 1986-90) and subsequent nationwide immunisation programme". Thesis, London School of Hygiene and Tropical Medicine (University of London), 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558367.
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Carr, Lucas J. "Short and long-term efficacy of an Internet-delivered physical activity behavior change program on physical activity and cardiometabolic disease risk factors in sedentary, overweight adults". Laramie, Wyo. : University of Wyoming, 2008. http://proquest.umi.com/pqdweb?did=1663060191&sid=1&Fmt=2&clientId=18949&RQT=309&VName=PQD.
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Ziemssen, Tjalf y Katja Thomas. "Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world". Sage, 2017. https://tud.qucosa.de/id/qucosa%3A35541.
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Alemtuzumab is a humanized monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS), given as two annual courses on five consecutive days at baseline and on three consecutive days 12 months later. Here we provide an update on the long-term efficacy and safety of alemtuzumab in RRMS, including realworld experience, and advances in our understanding of its mechanism of action. Recent data from the phase II/III extension study have demonstrated that alemtuzumab reduces relapse rates, disability worsening, and the rate of brain volume loss over the long term, with many patients achieving no evidence of disease activity. In high proportions of patients, preexisting disability remained stable or improved. Alemtuzumab is associated with a consistent safety profile over the long term, with no new safety signals emerging and the overall annual incidence of reported adverse events decreasing after the first year on treatment. Acyclovir prophylaxis reduces herpetic infections, and monitoring has been shown to mitigate the risk of autoimmune adverse events, allowing early detection and overall effective management. Data from clinical practice and ongoing observational studies are providing additional information on the real-world use of alemtuzumab. Recent evidence on the mechanism of action of alemtuzumab indicates that in addition to its previously known effects of inducing depletion and repopulation of T and B lymphocytes, it also results in a relative increase of cells with memory and regulatory phenotypes and a decrease in cells with a proinflammatory signature, and may further promote an immunoregulatory environment through an impact on other innate immune cells (e.g. dendritic cells) that play a role in MS. These effects may allow preservation of innate immunity and immunosurveillance. Together, these lines of evidence help explain the durable clinical efficacy of alemtuzumab, in the absence of continuous treatment, in patients with RRMS.
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DIOMEDE, LORENZO. "FATTORI UMORALI PROTETTIVI COME STRUMENTI PER LA GENERAZIONE DI VACCINI EFFICACI CONTRO L'INFEZIONE DA HIV". Doctoral thesis, Università degli Studi di Milano, 2012. http://hdl.handle.net/2434/168727.
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The present study includes several works which have common goal to further clarify the humoral correlates of protection against HIV infection, present in those populations that naturally can remain IgG-seronegative, despite a long-term exposure to HIV (ESNs), or are able to control for a long time the same infection (LTNPs, ECs). In fact, the first part of the thesis is concerned about the study of protective humoral parameters which would characterize a cohort of 45 HIV-infected individuals at different clinical stages (10 AI, Acute Infection, 10 LTNPs, 8 ECs, 7 AIDS, 10 HAART +); a cohort consisting of South African mothers infected with HIV subtype C, coupled with their infants, some of which are seronegative (as a particular ESN group), and finally, a cohort of women in Cambodian ESN, whose B cells, in their cervicovaginal secretions, were used to construct a library of Fab IgA phage-k/, which was screened for specificity to HIV-gp41. The results showed that heterogeneous humoral responses were observed in groups of HIV seropositive subjects. The high variability of total or gp41-specific IgA among all patients groups, supported their role as a biomarker. Infact, significant differences were detected in AI and in LTNP for IgA to gp41 and in IgG to gp120, respectively. Moreover, three domains of gp41, HR1, IDE and MPER, elicited antibodies that were effectively transmitted to ESN babies. In such babies, epitopes overlapping the 2F5 (ELDKWAS), but not the 4E10 epitope, were neutralization targets in two out of four viruses tested. Finally, the Fabs IgA from ESN women blocked efficiently transcytosis of HIV-1 with IC90 <50-150 ng ml-1. However, all results showed good neutralizing activity of ESN Fabs. The efficiency of the Fabs in protecting the epithelial cells from free-HIV and CD4+ cells HIV-infectied, suggests that the low concentration of IgA, present in genital secretions, could be active in vivo. Our findings highlight important epitopes in gp41 that appear to be associated with exposure, but without infection, and would be important to consider for vaccine design.
From these assumptions it has been possible to continue the study to design and produce immunogenic proteins which could elicit the humoral immune response, observed in the above categories. Thus we produced chimeric proteins, consisting of the carrier system of VLPs (Virus-Like Particles). In particular, have been used VLPs expressing regions and domains of HIV-gp41, produced in the first case in the baculovirus system, and in the second case, by the conjugation of gp41-peptides to VLPs, from bacteriophage Qβ, AP205. All results showed that sera from immunized animals showed a high reactivity with individual HIV proteins expressed in VLPs. Results of TZM-bl based neutralization assay show that combined sera from animals independently immunized with gp140- or full-length-gp41-expressing VLPs have an additive/synergistic effect in the neutralization activity of HIV pseudoviruses. The peptides to which aminoacid strings were added to either the C-terminus or N-terminus of core epitope in HR1 region prior to VLP coupling could induced a strong specific immune response and HIV-1 neutralizing antibodies; high level of gp41 specific antibodies and neutralizing activity were also raised against MPR region. Antibody-dependent cell cytotoxicity (ADCC) activity was induced by one of the two MPR epitopes, whereas no ADCC activity was associated to HR1 region. These results may have relevant implications for the development of new vaccinal approaches against HIV infection.
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Owen-Tittsworth, Michelle D. "Measuring teacher self-efficacy using English Language Learner Shadowing as a catalyst for implementation of two instructional strategies to support the academic language development of long-term English language learners". Thesis, Pepperdine University, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3588300.
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The purpose of this descriptive survey study was to (a) investigate the impact of ELL Shadowing on teachers' awareness of the academic language abilities and needs of Long-Term English Language Learners; (b) assess teacher-perceived proficiency in implementing Frayer Model and Think-Pair-Share Charting instructional strategies with English learners following specially designed professional development; (c) assess teacher self-efficacy to effectively address the academic language needs of English learners following specially designed professional development; and (d) investigate the academic language performance of Long-Term English Language Learners as a result of the Frayer Model and Think-Pair-Share Charting strategy implementation.
This study used an original survey created by the researcher consisting of 13 structured and 2 semi-structured questions that was administered after professional development on ELL Shadowing, the Frayer Model, and Think-Pair-Share Charting. The survey's 15 questions examined teacher self-efficacy in using the 2 instructional strategies to meet the needs of Long-Term English Language Learners, how ELL Shadowing impacted teachers' perspectives of English learners, and the impact of the 2 instructional strategies on English learners' performance following professional development.
The findings from this study indicated that: (a) the majority of teacher participants saw the benefit in ELL Shadowing increasing awareness of the academic needs of Long-Term English Language Learners and that these students often remain passively silent in the classroom; (b) teachers are slightly more comfortable using the Frayer Model than Think-Pair-Share Charting; (c) the majority of teacher participants saw the benefit in using the Frayer Model and Think-Pair-Share Charting to increase student talk, accountability, and Academic Language Development; and (d) in addition to professional development workshops, some teachers need ongoing support and coaching for full implementation of instructional strategies.
It was concluded that: (a) ELL Shadowing increases awareness of Long-Term English Language Learners; (b) English learner professional development can increase teacher efficacy for supporting English learners; (c) The Frayer Model and Think-Pair-Share Charting, when used in conjunction, increase academic language development for English learners; and (d) Effective professional development requires a systems approach in order to build teacher capacity and sustainability.
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Sysel, Annette M. "Investigation into the use of an epidural morphine sulfate and detomidine hydrochloride combination in horses : Part 1: efficacy in alleviation of hindlimb pain, Part 2: long-term systemic and local effects /". Thesis, This resource online, 1996. http://scholar.lib.vt.edu/theses/available/etd-08292008-063145/.
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Henning-Pugh, Mariette. "Helping four primary school children cope with the long term neurocognitive effects of a brain tumour : a case series pilot study investigating the efficacy of a school based cognitive remediation intervention program". Thesis, University of Surrey, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.616310.
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Deficits in social interaction, communication and repetitive patterns of behaviour are common characteristics of autistic spectrum disorders (Autism). Visuo-motor neurons (known as mirror neurons), that fire both when observing or executing goal directed actions, have been shown by research to play a role in motor action and intention understanding. This has led to a link suggesting that a dysfunction of mirror neurons may be involved in some aspects of Autism difficulties. Frequent research updates are providing a greater understanding and clarification for the important specification of this hypothesis. This leads the way to suggesting the possibility of the further development and support for novel interventions such as neurofeedback for this condition. This review represents a selective overview of core documents on the topic area. Declaration of Position My interest in the potential link between Autism and a dysfunctional mirror nemon system (MNS) was inspired by reading literature on the topic 'while I was completing a Masters in Neuropsychology. What became clear to me, both from the literature and from my limited clinical exposure, is the considerable heterogeneity of Autism. Furthermore, in the absence of distinct and consistent, nemo or physiological markers, accurate identification and diagnosis of autistic spectrum disorders can be problematic and consequently the ability of clinicians and researchers to detect this condition early in development is often restricted.
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Bartelt-Hofer, Jose Verfasser], Steffen [Akademischer Betreuer] [Fleßa, Steffen Gutachter] Fleßa, Walter [Gutachter] [Ried y Armin [Gutachter] Rhode. "Comparative Efficacy and Long-Term Cost-Utility of Combined Cataract and Minimally Invasive Glaucoma Surgery in German Patients with Primary Open-Angle Glaucoma / Jose Bartelt-Hofer ; Gutachter: Steffen Fleßa, Walter Ried, Armin Rhode ; Betreuer: Steffen Fleßa". Greifswald : Universität Greifswald, 2020. http://nbn-resolving.de/urn:nbn:de:gbv:9-opus-40897.
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Bartelt-Hofer, Jose [Verfasser], Steffen [Akademischer Betreuer] Fleßa, Steffen [Gutachter] Fleßa, Walter [Gutachter] Ried y Armin [Gutachter] Rhode. "Comparative Efficacy and Long-Term Cost-Utility of Combined Cataract and Minimally Invasive Glaucoma Surgery in German Patients with Primary Open-Angle Glaucoma / Jose Bartelt-Hofer ; Gutachter: Steffen Fleßa, Walter Ried, Armin Rhode ; Betreuer: Steffen Fleßa". Greifswald : Universität Greifswald, 2020. http://d-nb.info/122216180X/34.
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Zarrouki, Faouzi. "Dystrophine et système nerveux central : vers un traitement par saut d’exon des défauts cognitifs de la myopathie de Duchenne Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model Long term efficacy of AAV9-U7snRNA mediated exon 51 skipping in Mdx52 mice Gene therapy for central nervous system dysfunction in Duchenne muscular dystrophy". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLV102.
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La dystrophie musculaire de Duchenne, causée par des mutations dans le gène de la dystrophine, se traduit principalement par une dégénérescence de l’ensemble de la musculature squelettique et cardiaque mais également par des déficits cognitifs plus ou moins sévères. L’objectif de ce projet doctoral est de comprendre le rôle de la dystrophine dans le système nerveux central (SNC) à des fins fondamentales, mais aussi thérapeutiques, si les déficits observés peuvent être compensés. Notre laboratoire a développé une nouvelle classe d’oligonucléotides antisens : les tricyclo-DNA (tcDNA). Chez la souris modèle mdx, déficiente en dystrophine dans le muscle et le cerveau, nous avons montré que ces tcDNA, déjà très efficaces au niveau des muscles, ont la propriété de franchir la barrière hémato-encéphalique suite à une administration systémique et de restaurer une dystrophine tronquée fonctionnelle au niveau du SNC. Nous avons utilisé ces tcDNA afin d’explorer le comportement et l’évolution des fonctions cognitives des souris traitées par des injections systémiques ou intracérébroventriculaires. Nous avons montré que suite à une injection de tcDNA dans le cerveau, une restauration de la dystrophine cérébrale est possible et s’accompagne d’une correction de certains déficits émotionnels et cognitifs, suggérant la réversibilité d’une partie des atteintes centrales. Chez les souris traitées par voie systémique en revanche, et présentant une restauration plus limitée de dystrophine, seul le déficit émotionnel a pu être corrigé.Une seconde partie du projet était dédié à l’étude du rôle de la dystrophine dans la formation des clusters des récepteurs synaptiques GABAA, car ce mécanisme encore mal compris représente un biomarqueur pertinent d’une restauration fonctionnelle de dystrophine. Nous montrons que l’absence de dystrophine cérébrale perturbe le niveau d’expression et la formation des clusters de plusieurs sous-unités composant les récepteurs GABAA. Ces résultats prometteurs ouvrent des perspectives intéressantes sur des futurs thérapies permettant la correction des déficits émotionnels et cognitifs observés chez de nombreux patients atteint de dystrophie musculaire de DuchenneDuchenne muscular dystrophy mainly results in a degeneration of the entire skeletal and cardiac musculature but is also associated with various degrees of cognitive impairment. The objective of this doctoral project is to understand the role of dystrophin in the central nervous system (CNS) for both fundamental and therapeutic purposes if the defects observed are found to be reversible. Our laboratory is developing a new class of antisense oligonucleotides: tricyclo-DNA (tcDNA). In the mdx mouse model, we have shown that these tcDNAs have the ability to cross the blood-brain barrier and restore a functional truncated dystrophin in the CNS. We used these tcDNAs to explore the behaviour and evolution of cognitive functions of mice treated with systemic or locoregional injections. We have shown that following an injection of tcDNA into the CNS, a restoration of cerebral dystrophin is possible. In addition, this restoration allows the correction of some emotional and cognitive deficits. Interestingly, in mice treated intravenously and therefore expressing lower levels of dystrophin in the CNS, only the emotional deficit could be corrected.A second part of the project was dedicated to a better understanding of the role of dystrophin in the formation of GABAA receptor clusters. We show that the absence of cerebral dystrophin disrupts the level of expression and the formation of clusters of several subunits composing the GABAA receptors. These promising results open up interesting prospects for future therapies to correct the emotional and cognitive deficits observed in many patients with Duchenne muscular dystrophy
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Jörgensen, Fredrik. "The Law BusinessmanTM : Five Essays on Legal Self-efficacy and Business Risk". Doctoral thesis, Stockholms universitet, Företagsekonomiska institutionen, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-97625.
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The thesis challenges the notion of effectiveness of law as being based on the formal institutions of courts, law enforcement and written law. It argues that the best way to measure the effectiveness of law is the legal self-efficacy of laymen who are the end users of law. It presents a new perspective on the effectiveness of law. It turns the traditional perspective of studying the effects of legal institutions around and instead studies the effect of how individuals perceive their own ability to use law. This self-reflexive ability - legal self-efficacy - is the answer to the question “How comfortable are with communicating with legal terminology?”. The thesis makes several comparisons using the traditional perspective and legal self-efficacy and finds that legal self-efficacy is a better measure of legal effectiveness. This thesis analyzes 246 businesspeople in Russia and their risk behavior with regards to economic transactions in relation to legal self-efficacy. The theory behind legal self-efficacy is a combination of Luhmann’s theory of law as communication and Bandura’s concept of self-efficacy. The first paper applies the traditional approach. It analyzes the effect of legal efficiency on leverage and debt maturity for listed and non-listed companies. The second paper is describes the conceptual foundation of the legal effectiveness based on the individual. The third paper compares the effect of private order (including legal self-efficacy) and public order institutions on the granting of trade credit. The fourth paper analyzes the impact of legal self-efficacy and formal legal institutions on sanctions against clients in a comparative perspective. The final paper seeks out possible sources of legal self-efficacy. Legal self-efficacy can be used to better understand the interaction of individuals and law including such fields of research as behavioral accounting, behavioral law and finance, legal sociology and legal studies.
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Aupy, Philippine. "Le développement préclinique des tcDNA pour la Dystrophie Musculaire de Duchenne Evaluating the impact of variable phosphorothioate content in tricyclo-DNA antisense oligonucleotides in a Duchenne Muscular Dystrophy mouse model Identifying and avoiding tcDNA-ASO sequence specific toxicity for the development of DMD exon 51 skipping therapy Long term efficacy of AAV9-U7snRNA mediated exon 51 skipping in mdx52 mice The use of tricyclo-DNA for the treatment of Genetic Disorders Exon-skipping advances for Duchenne Muscular Dystrophy". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLV083.
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La Dystrophie Musculaire de Duchenne est une maladie génétique mortelle qui touche un garçon sur 3500. Elle se manifeste par une faiblesse musculaire progressive conduisant à une perte de la marche autour de l’âge de 10 ans, puis des problèmes respiratoires et cardiaques. Elle est due à des mutations dans le gène DMD conduisant à une absence de la protéine dystrophine. Il n’existe à l’heure actuelle aucun traitement satisfaisant. L’une des stratégies thérapeutiques les plus prometteuses pour cette maladie consiste à moduler l’épissage de l’ARN pré-messager. Cette stratégie appelée aussi « saut d’exon » utilise principalement des oligonucléotides antisens qui vont permettre de restaurer le cadre de lecture et ainsi entrainer la production de protéine.Le laboratoire Biothérapie des Maladies du Système Neuromusculaire a développé une nouvelle chimie d’oligonucléotide antisens, les tricyclo-DNA (tcDNA), ayant fait leur preuve pour effectuer un saut de l’exon 23 efficace dans des modèles murins de la DMD. En effet, les chercheurs de l’équipe ont pu démontrer la présence de saut d’exon et de restauration de dystrophine dans l’ensemble de la musculature et dans le système nerveux central, permettant d’obtenir une amélioration fonctionnelle. Lors de ma thèse, je me suis intéressée au développement pré-clinique d’un tcDNA ciblant l’exon 51 humain, puisqu’il s’agit de l’exon permettant de traiter la plus grande proportion de patients (13%).La première partie de mon projet a été consacrée à l’amélioration de la tolérabilité des tcDNAs à travers deux approches : la modification de la séquence et la modification du design de la molécule. En effet, la cause principale de la toxicité des tcDNAs est la formation de structures homodimériques associée à la présence de liens phosphorothioates (PS). Cette première étude a permis, d’une part, de démontrer qu’une modification de la séquence entraine une élimination des structures homodimériques et permet ainsi d’obtenir une meilleure tolérabilité de la molécule. D’autre part nous avons pu mettre en évidence qu’une diminution du contenu en liens PS permet de limiter l’apparition d’une toxicité à long terme sans impacter significativement l’efficacité.La deuxième partie de mon projet de thèse a été consacrée à l’optimisation de l’efficacité des tcDNAs. Pour cela deux approches ont été investiguées : d’une part l’amélioration de la biodisponibilité de la molécule et d’autre part l’optimisation de la séquence cible. Nous avons ainsi pu démontrer que la conjugaison d’un acide gras à un tcDNA entraine une amélioriation significative de sa biodistribution et de l’efficacité du tcDNA. En parallèle, un criblage de nombreuses séquences ciblant différentes régions de l’exon 51 a permis de sélectionner une séquence candidate présentant une efficacité nettement supérieure à celle de la séquence initiale. Cette séquence, conjuguée à un acide palmitique, a démontrée des résultats extremement encourageants pour les futurs essais cliniques et est actuellement en phase finale de développement précliniqueDuchenne Muscular Dystrophy is a fatal genetic disorder affecting 1/3500 newborn males. It is characterized by progressive muscle weakness causing loss of ambulatory functions and respiratory and cardiac failures. This disease is due to mutations in the DMD gene leading to complete loss of protein expression. There is currently no satisfactory treatment but one of the most promising therapeutic strategy is splicing modulation. This strategy also called “exon skipping” is achieved through the use of antisense oligonucleotides allowing a restoration of the reading frame, and thus leading to protein rescue.The laboratory Biothérapie des Maladies du Système Neuromusculaire has developped a new chemistry of antisense oligonucleotide, tricyclo-DNA (tcDNA). They have demonstrated the therapeutic potential of tcDNA in different mouse models of DMD. Indeed, after systemic treatment significant exon 23 skipping and dystrophin restoration were found in all tested muscles as well as in the central nervous system, leading to functional improvement. During my phD project, I worked on the pre-clinical development of a tcDNA targeting human exon 51, which could be applicable to a large proportion of DMD patients (13%).The first part of my project was dedicated to the improvement of tcDNA tolerability through the modification of the sequence itself and the modification of the chemical design. Indeed, the major cause of tcDNA toxicity is the formation of homodimeric structure associated with the presence of phosphorothioates linkages (PS). In this study, we were able to demonstrate that modification of the toxic sequence impairs homodimerization, thus suppressing toxicity. Moreover, we have demonstrated that a decrease in the PS content prevent the apparition of long term toxicity without impairing significatively exon skipping efficacy but.The second part of my project focused on the optimisation of tcDNA efficacy through improvement of their biodisponibility and optimisation of the targeted sequence. We first demonstrated that fatty acid conjugation to tcDNA significantly improves biodistribution and efficacy. In parallel, we screened numerous sequences targeting different regions of the exon 51 and selected a novel sequence with a significantly higher efficacy than the initial sequence. This novel tcDNA sequence, once conjugated with palmitic acid demonstrated extremely encouraging results for the treatment of DMD and we are currently finalizing its development for future clinical trials
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Patout, Maxime. "Evaluation des techniques pour la prise en charge diagnostique et thérapeutique de l'insuffisance respiratoire chronique A Randomized controlled trial on the effect of needle gauge on the pain and anxiety experienced during radial arterial puncture Long term survival following initiation of home non-invasive ventilation : a European study Neural respiratory drive predicts long-term outcome following admission for exacerbation of COPD : a post hoc analysis Neural respiratory drive and cardiac function in patients with obesity hypoventilation syndrome following initiation of non-invasive ventilation Polysomnography versus limited respiratory monitoring and nurse-led titration to optimise non-invasive ventilation set-up a pilot randomised clinical trial Chronic ventilator service Step-down from non-invasive ventilation to continuous positive airway pressure : a better phenotyping is required AVAPS-AE versus ST mode : a randomized controlled trial in patients with obesity hypoventilation syndrome Technological advances in home non-invasive ventilation monitoring : reliability of data and effect on patient outcomes Efficacy of a home discharge care bundle after acute exacerbation of COPD Prediction of severe acute exacerbation using changes in breathing pattern of COPD patients on home noninvasive ventilation Charasteristics and outcome of patients set up on high-flow oxygen therapy at home Trial of portable continuous positive airway pressure for the management of tracheobronchomalacia". Thesis, Normandie, 2019. http://www.theses.fr/2019NORMR115.
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L’insuffisance respiratoire chronique est un syndrome défini par une défaillance monoviscéralerespiratoire. Sa principale origine est aujourd’hui le syndrome obésité-hypoventilation qui concerne 4 à 5% des patients obèses. L’IRC est aussi le stade évolutif terminal de la bronchopneumopathie chronique obstructive qui touche 6 à 8% de la population adulte. L’incidence de ces pathologies et donc de l’insuffisance respiratoire est en augmentation constante. Dans cette thèse, nous avons évalué les nouvelles modalités diagnostiques et thérapeutiques qui pourraient améliorer la prise en charge des patients atteints d’insuffisance respiratoire chronique.Concernant la prise en charge diagnostique, nous avons montré que les données fournies par l’électromyographie de surface des muscles intercostaux, outil qui évalue le travail respiratoire, constituent un marqueur pronostique indépendant chez les patients atteints de bronchopneumopathie chronique obstructive. Nous avons également montré leur pertinence pour prédire l’efficacité clinique et l’observance à la ventilation non-invasive à domicile.Concernant la prise en charge thérapeutique, nous avons montré que l’utilisation d’un mode semi-automatisé de ventilation non-invasive a la même efficacité que celle de modes classiques en permettant une mise en place plus rapide du traitement. Nous avons également rapporté l’intérêt de l’oxygénothérapie à haut débit au domicile alors que ce traitement était utilisé jusque-là dans le seul cadre des soins intensifs. Enfin, nous avons rapporté les bénéfices de la pression positive continue au cours de l’effort chez les patients ayant une trachéobronchomalacie. Concernant le suivi des patients, nous avons montré que les données des logiciels de ventilation non invasive permettent de prédire la survenue d’une exacerbation sévère de BPCO mais que l’utilisation de la télémédecine chez les patients insuffisants respiratoires chroniques ne peut être encore pleinement intégrée dans la pratique clinique. Au cours de cette thèse, nous avons identifié de nouveaux outils physiologiques, de nouvelles modalités d’administration des traitements et de nouveaux outils de suivi à domicile, à même d’améliorer la prise en charge des patients insuffisants respiratoires chroniquesSingle-organ respiratory failure defines chronic respiratory failure. Obesity hypoventilation syndrome is the main cause of chronic respiratory failure and occurs in 4 to 5% of obese patients. Chronic respiratory failure is also the end-stage evolution of chronic obstructive pulmonary disease that has a prevalence of 6 to 8% in the adult population. The incidence of these diseases increases so does the incidence of chronic respiratory failure. In this thesis, we will evaluate novel diagnostic and therapeutic modalities that could improve the care of patients with chronic respiratory failure. Regarding diagnostic modalities, we have seen that evaluating the work of breathing with surface parasternal electromyography was an independent prognostic marker in patients with chronic obstructive pulmonary disease. We have also seen that it was a relevant tool to predict the clinicalefficacy and compliance to home non-invasive ventilation. Regarding therapeutic modalities, we have shown that the use of a semi-automatic mode of non-invasive ventilation had the same efficacy of a standard mode with a shorter length of stay for its setup. We have shown the relevance and feasibility of the use of high-flow oxygen therapy in the home setting whilst it was only used in intensive care units. Finally, we have shown the benefits of continuous positive airway pressure during exertion in patients with tracheobronchomalacia. Regarding patients’ follow-up, we have shown that the use of data from built-in software could predict the onset of a severe exacerbation of chronic obstructive pulmonary disease. However, we also show that the implementation of tele-medicine in patients with chronic respiratory failure cannot be included in daily clinical practice yet. In this thesis, we have identified novel physiological tools, novel ways to administer treatments and novel follow-up tools that can improve the management of patients with chronic respiratory failure
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Chiang, Kwo-Tsao y 江國超. "Analysis of Long Term Prognosis and Efficacy of TURP in Taiwan". Thesis, 2011. http://ndltd.ncl.edu.tw/handle/72400004638440047046.
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碩士國立中山大學
醫務管理研究所
99
BPH（Benign prostate hyperplasia）is one of the most common chronic diseases in aging male around the globe. TURP（Transurethral Resection of Prostate）remains the gold standard procedure of choice in BPH treatment. But limited literatures regarding the late complication of TURP was available. For understanding the long term follow up result after TURP, and predict the risk factors for re-intervention, we accessed the hospital claims for TURP from the National Health Insurance database, utilizing data from 2001 to 2007 , in 2001, 2002, 2003 TURP cases, we followed each cohort for 5 years to evaluate the late complications. We also examined the association between the characteristics of patient, hospital and the long term prognosis. In this study we found that from 2001to 2003, totally 1,225 patients under went TURP surgery, with the average age 71.52 ± 7.65 years (47-94 years). Among these cases, 140 patients (11.43%) experienced secondary surgery. Of the 140 secondary surgery patients, 71 received a secondary TURP, 35 received urethral stricture related surgery and 34 received bladder neck contracture related surgery. The study revealed both the characteristics of the patient and the hospital did not show significantly effect to the long term prognosis. In prediction the risk factors of the secondary surgery, the logistic regression analysis revealed those hospitals located at the central part of Taiwan compared to those at northern part of Taiwan showed a relative risk of 0.58, a significant trend of lower risk for secondary surgery. Otherwise, except this geographic location difference, other characteristics of the patient and the hospital show no significantly risk to the post-TURP second surgery. Conclusion of our study, the result of TURP surgery in Taiwan was fairly equal to that in advanced countries. Patient comorbidity, treated in different level, ownership hospitals resulted no significant difference in post-TURP prognosis.
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江玲玲. "The Efficacy of Physical Therapy in Patients with Long-term Mechanical Ventilation". Thesis, 2003. http://ndltd.ncl.edu.tw/handle/93721551351381291467.
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碩士國立臺灣大學
物理治療學研究所
92
Background and Purpose: In patients with prolonged ventilator used, previous studies have shown that pulmonary rehabilitation could decrease the rates of hospital mortality and increase ventilatory independence, however, its effect on functional ability and quality of life have not yet been reported. The purpose of this study was to investigate the effects of 6-weeks physical therapy interventions on respiratory muscle and peripheral muscle strengths, functional ability, quality of life and weaning outcomes in patients with long-term ventilator used. Methods: Thirty-four patients from Respiratory Care Centers with long-term mechanical ventilation were recruited and randomized into either treatment (n=17) or control (n=17) groups for the study. Treatment group received physical therapy interventions, which included muscle strengthening for upper/lower extremities, ambulation training, and functional activity (self-directed care) training, 5 times/week for a total of 6 weeks by a physical therapist. Muscle strengths of the respiratory and upper/lower extremities, functional status (by Barthel Index BI； and Functional Independent Measure FIM), quality of life (by Short Form-12, SF-12) and weaning outcomes were measured at baseline, and the end of the 3rd and 6th weeks of the study period for both groups. Nonparametric Mann-Whitney Test and Friedman Repeated Measures Analysis of Variance on Ranks Test were used to compare variables between and within the groups, respectively. Results: Baseline data were similar between groups. At the end of the 3rd and 6th week of physical therapy interventions, strength of the respiratory muscles and upper/lower extremities significantly increased in the treatment group compared to that of baseline and the control group. The treatment group also showed significant improvements in the total scores of BI and FIM, and SF-12 mental component score compared to that of the baseline and the control group at the end of the 3rd and 6th week of physical therapy interventions. Although the weaning outcomes were not significantly different between the two groups, the treatment group did show prolonged ventilator-free time. Conclusion: Six-week physical therapy intervention could increase muscle strength, enhance functional ability, partially improve the quality of life, and increase the ventilator-free time in patients with long-term ventilator used. Further follow-up studies are needed.
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Le, Phu. "Efficacy of Mouth Care Education to Improve the Oral Health of Residents of Long Term Care Homes". Thesis, 2011. http://hdl.handle.net/1807/27350.
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Objective: To assess the efficacy of personal support worker (PSW) mouth care education to improve the oral health of residents of long term care homes. Methodology: Experimental PSWs received mouth care education at baseline before taking the knowledge test. PSWs‟ mouth care knowledge was measured using a 20-item knowledge test at baseline, post-test (supervised); 6-months (un-supervised). Residents‟ oral health outcomes assessed at baseline and 6-months using the modified Plaque Index and modified Gingival Index. Results: Experimental PSWs‟ post-test knowledge (n=32;M=17.59;SD=1.43) significantly increased from pre-test (M=15.34;SD=2.10), F(2,72)=4.90;p<.05. 39 control residents and 41 experimental residents participated. Experimental residents‟ PI significantly decreased at 6-months compared to baseline, F(1,156)=5.52;p<.05, there was no significant difference in their GI between baseline and 6-months, F(1,156)=3.29;p=.07. Conclusion: PSWs‟ mouth care knowledge significantly increased after receiving mouth care education and was sustained over six months. Only experimental residents‟ PI significantly improved after 6 months.
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Mugford, J. Gerry. "Efficacy of long-term psychotherapy in the management of persons living with HIV/AIDS /". 2002.
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43
Yang, Ching Wei y 楊晉瑋. "Efficacy of traditional Chinese medicine-integrated institutional long-term care system: a preliminary report". Thesis, 2018. http://ndltd.ncl.edu.tw/handle/cb585t.
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碩士長庚大學
中醫學系傳統中醫學
106
Objective: To investigate the therapeutic efficacy of traditional Chinese medicine (TCM)-integrated institutional long-term care system. Materials and Methods: Thirty-two patients in the nursing home of Taoyuan Chang Gung memorial hospital were included in this prospective study. To explore the role of TCM in long-term care system, quality of life, heart rate viability (HRV),frequency of transferred to the emergency department or admission, and satisfaction of caregivers were used to evaluate the efficacy of TCM. The results were analyzed by paired t-test or Chi-square test via SPSS (version 19.0) and P-value less than 0.05 was significant. Results: The quality of life such as constipation (P=0.008), lower back pain (P=0.028), and depression (P=0.020) were improved. HRV exam showed elevated levels of SDNN (P=0.012), RMSSD (P=0.011), TP (P=0.024), LF (P=0.015), or LF/HF (P=0.012). There was no difference in the number of emergency and hospitalization before and after TCM intervention.More than fifty percent of primary caregivers satisfied and agreed that TCM was helpful for patients in long-term care facility. Conclusion: This article was the first pilot study to explore the therapeutic efficacy of TCM combined with conventional western medicine among patients in long-term care system in Taiwan. We found the improvement of quality of life and autonomic nervous function. The efficacy of TCM for elderly disability was agreed by caregivers. No severe adverse complications happened during TCM treatment. It will need more patients and more rigorous clinical studies to confirm the true adjuvant medical value in the future. Keywords: long-term care, elderly disability, traditional Chinese medicine, quality of life, heart rate viability
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Xiao, Dan. "Novel Delivery Systems of Nisin to Enhance Long-term Efficacy against Foodborne Pathogen Listeria monocytogenes". 2010. http://trace.tennessee.edu/utk_graddiss/927.
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Novel intervention strategies such as food grade antimicrobials are used to enhance food safety. Nisin is a widely used naturally occurring antimicrobial effective against many pathogenic and spoilage microorganisms. However, its antimicrobial efficacy in food matrices is much reduced because of interactions with food components. Novel delivery systems may overcome this problem by protecting nisin in capsules and releasing it in a controlled manner. The overall goal of this research was to develop delivery systems of nisin to improve its long-term antimicrobial effectiveness. The first objective was to develop a low-cost method to extract nisin from a commercial preparation containing ~2.5% nisin. The best extraction yield was observed at 6 mg solids/mL 50% v/v ethanol. The nisin extract, after adjusting to 70% v/v ethanol, was dissolved with 2% zein (corn prolamins) and different amounts of Tween 20, glycerol, and thymol (another naturally occurring antimicrobial) for spray drying, a practical encapsulation method. Spray-dried capsules were characterized for release profiles of nisin at different pH conditions. Spray drying inlet temperature was first studied at 75 to 120°C, and the greatest sustained release of nisin was observed for capsules produced at 105°C, which was used in rest of this study. The impacts of Tween 20 and glycerol supplemented in spray-drying formulations were studied next. Addition of either 0.05% Tween 20 or glycerol in the spray-drying solution reduced the burst release of nisin at pH 6.0. Capsules with a higher amount of Tween 20 showed more complete release of nisin at pH 8.0, while glycerol had no apparent impact. The most sustained release of nisin at pH 6.0 was observed for capsules produced with both thymol and glycerol. Various capsules were then studied for their ability to inhibit the growth of Listeria monocytogenes at pH 6.0 during incubation at 30°C. Un-encapsulated nisin and thymol showed inhibition only for 12 h, while capsules with nisin and thymol containing either low or medium level of glycerol inhibited L. monocytogenes for >96 h. Our antimicrobial delivery systems, based on food grade ingredients and practical processes, have potential for practical application to enhance microbial safety and extend the shelf-life of foods.
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Silva, Adriana Manuel Reis. "Evaluation of long-term efficacy of intravitreal anti-VEGF therapy in neovascular AMD in clinical practice". Master's thesis, 2015. https://repositorio-aberto.up.pt/handle/10216/88164.
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Silva, Adriana Manuel Reis. "Evaluation of long-term efficacy of intravitreal anti-VEGF therapy in neovascular AMD in clinical practice". Dissertação, 2015. https://repositorio-aberto.up.pt/handle/10216/88164.
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LIN, CHIA-YING y 林佳瑩. "The Efficacy of Cognitive Training Program among Elderly with Cognitive Function Decline in Long-term Care Facility". Thesis, 2017. http://ndltd.ncl.edu.tw/handle/v4h568.
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碩士國立臺北護理健康大學
護理研究所
106
Prevalence of dementia is growing rapidly as the aging population increases. The number of the elderly with dementia in long-term care facility is higher than those who live in the community. The elderly may feel frustrated and display depression and anxiety when they start to have cognitive decline which lead to difficulties in the activities of daily living. Developing strategies to improve cognitive function for the elderly is important. The aim of this study was to evaluate the efficacy of cognitive training program for cognitive function, depression, well-being, self-esteem and quality of life among the elderly with a decline in cognitive function in long-term care facility. A quasi-experimental design was used. Participants were older residents with cognitive function decline in a long-term care facility in eastern Taiwan. A total of 50 participants aged 65 years and older were assigned to experimental group (n=25) or control group (n=25). The experimental group received cognitive training program for 60 minutes per session, twice a week for 12 weeks delivered by a trained nurse; and the control group received routine care. Cognitive function, depression, well-being, self-esteem and quality of life were assessed at pretest, week 4, week 8, and week 12. Descriptive statistics was used to analyze demongraphical data, and repeated measures ANOVA was used to analyze the main outcomes. After 12-week cognitive training program, the experimental group had improvement on cognitive function, well-being, and self-esteem over time, and these improvements were significantly different at week 4, 8, and 12 compared to those of the control group. Depression was decreased in the experimental group over time and reached a statistically significant difference at week 8 and week 12 compared to the control group. However, there was no significant difference on quality of life between groups. The cognitive training program can be applied to improve cognitive function, depression, well-being and self-esteem for the elderly with cognitive function decline in long-term care facility.
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Doccini, Viola. "Efficacy, Long-term Efficacy and Tolerability of Lacosamide, Stiripentol, Fenfluramine Hydrochloride and Levetiracetam in children, adolescents and young adults with different types of epilepsy". Doctoral thesis, 2022. https://hdl.handle.net/2158/1293559.
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ABSTRACT
INTRODUCTION. Epilepsy is one of the most common chronic neurological disorders characterized by the presence of spontaneous and recurrent seizures and it affects 1% of the population worldwide. Up to 30% of patients continue to have seizures despite an adequate and well-tolerated treatment with antiepileptic drugs (ASMs), used singularly or in combination. These individuals are regarded as having refractory or drug- resistant epilepsy. In 2010, an Internationally accepted definition of refractory epilepsy was proposed by a Task Force of International League Against Epilepsy (ILAE) as “failure of adequate trials of two tolerated, appropriately chosen and used ASM schedules to achieve sustained seizure freedom”. Regardless of the advances in the field of epilepsy and the acquisition of new antiepileptic drugs, the proportion of drug-resistant patients remain unchanged.
Dravet syndrome (DS) is a rare, drug-resistant, developmental epileptic encephalopathy with onset in infancy characterized by multiple types of frequent, disabling epileptic seizures, developmental delay/cognitive impairment and an increased risk of sudden unexpected death in epilepsy (SUDEP). In more than 80% of patients, a sodium voltage-gated channel alpha subunit 1 gene (SCN1A) genetic variant can be demonstrated, although diagnosis is based on clinical criteria.
Idiopathic generalized epilepsies (IGEs) are the most common group of epilepsies in children and adolescents and include four well-characterized epilepsy syndromes: childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, and IGE with generalized tonic–clonic seizures only. Distinctive features of IGE syndromes are typical age of onset, specific generalized seizures type, normal background EEG activity and interictal generalized spike-and-wave (GSW) discharges in the absence of any brain lesion and with normal developmental skills.
Lacosamide (LCM) is a third generation ASM approved by European Medicines Agency (EMA) and US Food and Drug Administration (FDA) as both monotherapy and adjunctive therapy in treatment of focal seizures, with or without bilateral tonic-clonic seizures, in patient older than 16 (EMA) or 17 (FDA) years old.
Stiripentol (STP) is a third generation ASM indicated as adjunctive therapy in Dravet syndrome, whose seizures are not adequately controlled with clobazam and valproate.
Fenfluramine (FFA) Hydrochloride is fourth generation ASMs, recently noticed as effective for the treatment of convulsive seizures and non-convulsive SE in DS. In the 2019, Zogenix supported an EAP of FFA in patients with a clinical diagnosis of DS, without echocardiographic signs of cardiac valve disfunction and pulmonary arterial hypertension and in June 2020 FDA approved FFA for the treatment of seizures in DS.
Levetiracetam (LEV) is one of the most widely used ASMs for both adults and children. It is approved by EMA and FDA as adjunctive therapy in IGEs with myoclonic or tonic-clonic seizures in patients >12 years, as monotherapy in focal seizures in patients >16 years and as add-on therapy in focal or focal to bilateral tonic- clonic seizures in children and adults.
AIM OF THE STUDY. To evaluate efficacy, long-term efficacy and tolerability of LCM, STP, FFA, or LEV in a cohort of children, adolescents and young adults with different types of refractory epilepsies, including focal and generalized forms and epileptic encephalopathies such as DS.
METHODS. Patients treated with Study Drugs as therapy for different, refractory, types of epilepsy and seen at the Neuroscience Center of Excellence-Meyer Children Hospital in different period time were included in our studies. Data were retrospectively reviewed. Responder rate, relapse free survival and retention rate were calculated. Tolerability was assessed by reporting adverse events.
RESULTS. Lacosamide: A total of 88 individuals (41 female) aged 4 months to 18 years (median 10.5 years; mean ± SD 10.6 ± 4.8 years) received add-on LCM treatment for refractory epilepsy. Thirty-four patients (38.6%) were responders with a median time to relapse of 48 months. Nine (26.4%) of the 34 responders were seizure-free. For all 88 patients, the probability of remaining on LCM without additional therapy was 74.4% at 6 months, 47.7% at 12 months, 27.9% at 24 months, 18.0% at 48 months, and 8.2% at 72 months of follow-up. No statistically significant differences in relapse and retention time were observed with regard to epilepsy and seizure types, duration and course of epilepsy, number and type of antiepileptic
drugs (AEDs; sodium channel blockers vs others) used in add-on. The most frequent adverse events were dermatological (4/11) and behavioral (3/11).
Stiripentol first study: A total of 132 individuals aged from 5 months to 43 years received add-on STP, including 30 patients with DS. The median follow-up was 14.8 months (range=4 months-18 years, interquartile range=25.72). Twenty-nine individuals (22%) received more than two ASMs. Benzodiazepines, mainly clobazam, were the most commonly used add-on drugs. Sixty-six patients (50%) were responders, and 13 of them (9.8%) were seizure-free. Responder rate was higher in the genetic etiology group (57%), especially in DS (18/30; 60%), and in patients with refractory focal onset epilepsy without bilateral tonic-clonic seizures (5/15; 33%). The median relapse-free survival was 27 months in the 66 responders. The median time to STP failure was 24.6 months in all 132 individuals.
Stiripentol second study: We expanded our analysis to a larger cohort of 196 patients with long-term follow-up. We observed a responder rate of 53% including seizure freedom in 9%. Etiology was associated with sustained response over time, with DS being the etiology with the highest responder rate (64%) at 48 months compared with syndromes with other genetic causes (13%) or unknown etiology (38%). A higher responder rate over time was also observed in patients with generalized (44%) and combined focal and generalized epilepsies (28%) than in patients with focal epilepsies (20%). The highest relapse free-survival was observed when STP was initiated at the youngest age (0-4 years) or in adulthood.
Fenfluramine:
Levetiracetam: A total of 88 patients with IGEs aged from 3.4 to 33.8 years, started LEV as monotherapy or add-on therapy. The median follow-up was 7.3 months (range=0.5-106 months). Thirty-four individuals (46.6%) received more than two ASMs. Thirty-five patients (39.8%) were responders, and 26 of them (29.5%) were seizure-free. The median time to LEV failure was 42 months and the median retention time was 10 months in all 88 individuals. A higher retention time was observed in patient older than 14 years. Fifty-
Fifty-two patients were enrolled, with a median age of 8.6 years (interquartile range
[IQR] = 4.1-13.9). Forty-five (86.5%) patients completed the efficacy analysis. The median follow-up was 9.0
months (IQR = 3.2-9.5). At last follow-up visit, there was a 77.4% median reduction in convulsive seizures.
Thirty-two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction,
and five (11.1%) were seizure-free. The most common adverse event was decreased appetite (n = 7, 13.4%).
No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no
correlation between type of genetic variants and response to FFA.
seven patients changed their therapy regimen by replacing LEV with another ASMs. Fourty-two (73.4%)
remained responders at the last evaluation. About patients that replaced LEV with VPA or ETS, 23/27 (85.2%)
or 9/12 (75%) were responders, respectively (p=0.19).
neurological/psychiatric (17/18).
CONCLUSIONS. Lacosamide:
This study documents a real-world progressive and significant loss
Stiripentol: suggest that STP is an effective and well-tolerated therapeutic option not only in DS but also in other epilepsy syndromes with or without an established genetic etiology, with sustained response over time.
Fenfluramine:
Levetiracetam: This study suggests that LEV did not result in a satisfactory clinical response in IGEs, considering their known good prognosis
The most frequent adverse events were
of LCM efficacy over time in a pediatric population. Further prospective studies on larger populations are
required to confirm the remarkable loss of LCM efficacy over time.
These studies
In this real-world study, FFA provided a clinically meaningful reduction in convulsive
seizure frequency in the majority of patients with DS and was well tolerated.
Further confirmations based on prospectively or controlled designed studies with larger population are
required to confirm our data.
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van, Zon Lorraine. "The Efficacy of a Volunteer-Administered Cognitive Stimulation Program in Two Long-Term Care Homes: A Randomized, Controlled Study". Thesis, 2014. http://hdl.handle.net/1974/12210.
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Older adults who maintain their cognitive skills and abilities are able to live more independently than those whose skills have deteriorated. The costs (money, time, personnel) associated with providing cognitive stimulation programs to residents in long-term care homes often prohibit the delivery of these programs. The present study explored the efficacy of using volunteers to administer a stimulation program in two long-term care homes. The program focused on stimulating reasoning, attention, and memory abilities using uncomplicated, pen-and-paper exercises. Thirty-six resident participants and 16 volunteer participants were randomly assigned to one of two parallel groups, either the control or stimulation group. For eight weeks, three times each week, control group participants met for standard “friendly visits” (casual conversation between a resident and volunteer) and stimulation group participants met to work through a variety of exercises meant to stimulate the cognitive abilities of residents. Results were analyzed using a 2-way ANOVA and indicated statistically significant Group x Time interactions for Verbal Memory, Non-Verbal Memory, Learning, and in a screening test for verbal fluency. Volunteers completed a post-study questionnaire which indicated that the volunteers in the stimulation group found their skills-based interactions more stimulating for residents. Therefore this study demonstrates that a volunteer-administered cognitive stimulation program can provide measurable gains in the cognitive abilities of older adults. Further studies concerning the role of volunteers in the maintenance of the cognitive abilities of older adults are recommended.Thesis (Master, Education) -- Queen's University, 2014-05-29 07:07:01.042
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Shea, Corey Matthew. "Evaluation of the efficacy and long-term safety outcomes of first generation drug-eluting stents in off-label indications". Thesis, 2014. https://hdl.handle.net/2144/15044.
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FDA approval of drug-eluting stents (DES) in 2002, was based on data obtained from several pivotal, short-term (< one year) randomized control trials that evaluated their efficacy in reducing in-stent restenosis when used in treatment of coronary artery lesions compared with bare metal stents (BMS). These trials excluded patients with complex coronary lesions. When the FDA approved use of DES in treatment of coronary artery lesions, the on-label indications only applied to a very limited subset of simple lesions.
Immediate advantages of DES were observed in clinical practice for on-label indications, specifically in their ability to significantly reduce in-stent restenosis after PCI. The increased short-term safety and efficacy seen in on-label clinical cases soon led clinicians to expand the use DES to more complex lesions. These complex indications, not included in the pivotal FDA trials, are considered off-label. Off-label indications include bifurcation lesions, ostial lesions, lesions greater in length and diameter than those approved by the FDA, implantation in saphenous vein grafts, and lesions in the left main coronary artery. Currently, DES use for treatment of lesions presenting off-label indications may comprise as much as 60% of clinical cases. However, early evidence that DES may play a role in adverse safety outcomes, has led many to question the use of DES outside their on-label indications.
This paper sought to evaluate some of the current research investigating first generation DES use in four different off-label indications: coronary artery bypass graft lesions, saphenous vein graft lesions, ostial lesions, and chronic total coronary occlusions. In particular, it looked at studies, which compared the efficacy and clinical outcomes of DES and BMS treatment of each of the different lesion types.
The results of this evaluation were very promising in that of the four specific off-label indications evaluated, all of them showed to be superior in reduction of neointimal growth and subsequent in-stent restenosis. Additionally, DES treatment of left main coronary artery lesions, saphenous vein graft lesions, and chronic total coronary occlusions showed to be superior in reducing the incidence rate of major adverse cardiac events and target vessel revascularization over various follow-up durations. The only scenario that DES did not prove to be superior to BMSs was the treatment of ostial lesions.
Long-term randomized control trials with large study populations should be performed to further elucidate the effects of DES treatment of specific off-label lesions.