Les études de pharmacoépidémiologie consistent à étudier l’effet de médicaments en vie réelle, et sont menées de plus en plus souvent sur bases de données médico-administratives. Ce sont principalement des études observationnelles, et sont donc soumises à des biais liés à des facteurs de confusion. Ces facteurs ne sont pas toujours recueillis dans les bases de données médico-administratives qui sont implémentées à d’autres fins que la recherche. Des plans expérimentaux self-controlled designs (où le patient est son propre témoin, et dont les principaux sont le case-crossover et le self-controlled case-series) permettent d’étudier l’effet transitoire d'expositions brèves sur des évènements à début brutal. Ils sont soumis à certaines conditions d’application. Ils ont la particularité de réaliser des comparaisons sur différentes périodes plutôt que sur différents groupes de patients, permettant ainsi de prendre en compte des facteurs de confusion, y compris non mesurés, et qui ne varient pas entre les périodes observées. Ces méthodes ont montré leur utilité pour pallier l’absence de randomisation, et leur utilisation est recommandée quand leurs conditions d’application sont remplies. Nous avons étudié la fréquence d’utilisation des self-controlled designs en pharmacoépidémiologie sur bases de données, les opportunités manquées d’utilisation et leur usage approprié au regard de leurs conditions d’application, ainsi que la qualité de l’information rapportée dans les articles. Nous avons montré que leur utilisation est rare, que 15% des articles correspondent à des situations d’opportunité où ces méthodes auraient pu être implémentées, que 34% des case-crossover et 13% des self-controlled case-series étaient appliqué de façon inapproprié, et que pour 16% des articles la méthode aurait pu être adaptée pour être valide. Un usage plus approprié permettrait de contribuer à l’investigation en pharmacoépidémiologie tout en bénéficiant des avantages de ces méthodes en particulier sur bases de données de santé. / Pharmacoepidemiology consists in the study of efficacy or safety of drugs in real life, with the use more and more frequently of medico-administrative databases. Study designs are generally observational, thus they are prone to confounding bias. Confounders are not systematically collected in databases, which are implemented for other purposes than research. Self-controlled designs (mainly represented by case-crossover and self-controlled case-series, and in which the patient acts as his own control), have been developed for the study of intermittent exposure with short-term effect on abrupt onset event. They require that validity assumptions being fulfilled. They consist in the comparison over different periods, rather than different groups of patients, thus allowing for confounding factors, also if not measured, which are invariant over observed periods. Such designs have been proved useful in observational studies in the absence of randomization, and their implementation is recommended in case of validity assumptions are fulfilled. We studied their frequency of use in pharmacoepidemiology in healthcare databases, missed opportunities for use, inappropriate use with respect to validity assumptions, as well as quality of reporting. We showed that self-controlled designs are rarely used, that opportunity for use was founds in 15% of articles where such methods could have been implemented, that 34% of case-crossover and 13% of self-controlled case series were inappropriately used, and that the method could have been adapted to be valid in 16% of articles. A more appropriate use of self-controlled designs could contribute to improve investigation in pharmacoepidemiology, while beneficiating from their advantages, especially in healthcare databases.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Epilepsy is the most common neurologic condition seen in children. Focal cortical dysplasia (FCD), a seizure disorder characterized by abnormal cortical laminar development, comprises approximately 75% of medically intractable epilepsies in the pediatric population. A greater appreciation of the pathology and intrinsic properties of the epileptogenic zone may help in understanding why FCD lesions are drug‐resistant, and could potentially lead to more effective treatments in the pediatric population. Neuronal support cells such as microglia and astrocytes have shown to have a role in FCD pathology. These cells are also activated during aging and traumatic brain injury as evidence by morphological change. This study aims to characterize the spatial distribution of microglia and astrocytes using immunohistochemistry in dysplastic tissue of eight male pediatric patients diagnosed with FCD. Cortical specimens from patients who underwent surgical resection of focally dysplastic cortex at Phoenix Children’s Hospital between 2008 and 2014 were examined using immunohistochemistry. Primary antibodies against GFAP and Iba1, as well as structural staining using hematoxylin and eosin (H&E), were incubated on sections and further analyzed using bright‐field microscopy. A pattern of perivascular activated microglia was observed in five patients around at least one blood vessel, while a pattern of non‐localized ramified microglia was observed in the other three patients. No identifiable pattern of astrocytic distribution was found. Thus, distinct patterns of microglia, rather than astrocytes, suggest dual underlying mechanisms of epileptogenesis.

Objectives: This thesis included 6 manuscripts which focused on the analysis of adverse events following immunization (AEFIs), including general health services utilization (emergency room (ER) visits and hospital admissions) and specific diagnoses (e.g. febrile convulsions). The main objectives of this research were: 1) To demonstrate the utility of the self-controlled case series (SCCS) design coupled with health administrative data for studying the safety of vaccines; 2) Introducing an innovative approach using relative incidence ratios (RIRs) within an SCCS analysis to identify risk factors for AEFIs and to overcome the healthy vaccinee bias; and 3) To demonstrate how SCCS and RIR analyses of health services outcomes in health administrative data can provide important insights into underlying physiological and behavioural mechanisms. Data Sources: This work utilized Ontario health administrative data housed at the Institute for Clinical Evaluative Sciences (ICES). The study included all children born in Ontario, Canada between 2002 and 2011 (over 1 million children). Vaccinations were identified using OHIP fee for service billing codes for general vaccination. Admissions and ER visits for any reason were identified in the Discharge Abstract Database (DAD) and National Ambulatory Care Reporting System (NACRS). Primary reasons for admissions and ER visits were investigated using ICD-10-CA codes reported in the DAD and NACRS databases. Statistical Methods: The self-controlled case series design (SCCS) was used to calculate the relative incidence of admissions, ER visits and other AEFIs. To investigate relative incidence for AEFIs across risk groups of interest, as well as addressing the healthy vaccinee effect bias, RIRs were calculated. RIRs are the ratio of incidence ratios in a subgroup of interest relative to a designated reference group. Results and Conclusions: The combined approach of using the SCCS design and RIRs to identify risk factors and overcome the healthy vaccinee bias proved to be a powerful approach to studying vaccine safety. Future work will be important to characterize the performance and validity of the SCCS + RIR approach in the presence of increasing levels of confounding and differing manifestations of the healthy vaccinee bias, as well as to elucidate the biological and behavioural mechanisms underlying our findings.

Este estudo buscou verificar a ocorrência de casos de cisto radicular em incisivos superiores decíduos traumatizados e descrever suas características relacionadas à criança, ao dente, ao trauma e ao cisto. Para tanto, realizou-se um levantamento das informações clínicas e radiográficas, de 2498 prontuários de pacientes atendidos na Clínica do Centro de Pesquisa e Atendimento de Traumatismo de Dentes Decíduos da Disciplina de Odontopediatria da FOUSP, no período de 1998 a setembro de 2013. Foi utilizado o método exploratório descritivo de uma série de casos. Foram avaliados 30 prontuários com casos de cistos, totalizando 32 incisivos superiores decíduos traumatizados com cisto. A ocorrência de cisto em pacientes com incisivos superiores decíduos traumatizados foi de 1,2%. Os resultados mostraram que a maioria dos cistos acometeram o gênero feminino (59,4%), os incisivos centrais superiores decíduos (93,8%), em crianças maiores de 5 anos (81,2%), mas que sofreram traumatismos com menos de 4 anos de idade (81,2%). A maioria dos casos não apresentou alteração clínica que levasse a suspeita de lesão cística, pois não foi encontrado em 90,7% retração gengival, 65,6% alteração de cor da mucosa vestibular, 65,6% fistula, 75% abscesso, 56,2% abaulamento gengival, 78,1% depressão da mucosa vestibular e 56,3% flutuação cistíca. A alteração clínica mais frequente foi a alteração de cor da coroa (56,3%). A média da idade do paciente no momento do trauma foi de 2,7 anos e do diagnóstico do cisto de 5,9 anos, sendo que a média de tempo do trauma até o diagnóstico do cisto foi de 2,8 anos. Em 46,9% dos dentes ocorreu trauma dental. A maioria dos traumas foram de baixa severidade (59,3%). Em 46,8% dos casos, o dente decíduo envolvido na lesão apresentava maior formação radicular que seu homólogo e em 62,5% o germe sucessor do dente decíduo com a lesão cística encontrava-se em estágio de Nolla anterior que o homólogo. A maioria das lesões císticas (81,2%) não envolveu dentes adjacentes, mas promoveram deslocamento de germes em 56,2%. Na dentição permanente foram encontrados repercussões em 31,3,% dos casos e retenção prolongada do permanente em 15,6%. Diante dos achados deste estudo observou-se que o cisto radicular em incisivos decíduos traumatizados é raro, assume um perfil menos agressivo, de crescimento controlado e necessitando de um tempo longo para se desenvolver. Além do mais, parece causar sequelas menos danosas às dentições, influenciar no processo de rizólise e rizogênese e estar relacionado a traumas de baixa severidade. O diagnóstico deve ser realizado pelos achados radiográficos, sendo que a reabsorção radicular externa sem formação óssea, assimetria no tamanho do folículo do germe dentário sucessor ao dente envolvido com a lesão cística e o folículo homólogo, bem como a diferença de altura e/ou posição entre os germes dentários homólogos deveriam ser considerados como sinais radiográficos no diagnóstico de cistos radiculares. / The present study aimed to verify the occurrence of radicular cyst in traumatized primary upper incisors and describe their characteristics in relation to the children, teeth, trauma and cysts. The survey of 2, 498 patients that presented and were treated at the Research and Clinical Center of Dental Trauma in Primary Teeth of the School of Dentistry of the University of Sao Paulo from 1998 to September 2013 was carried out, in order to collect clinical and radiographic information. A descriptive and exploratory approach was taken in the study. A total of thirty clinical records involving radicular cysts included thirty two traumatized primary upper incisors were studied in detail. The overall occurrence of cysts in patients with traumatized primary incisors was 1.2% with females affected more (59.4%) often than males 93.8% involved the upper central incisors. 81.2% of the children were older than 5 year of age but suffered traumatic injuries before 4 years old. In most cases, gingival recession (90.7%); color change of the vestibular mucosa (65.6%); fistula (65.6%); abscess (75%); gingival bulging (56.2%); depression of the vestibular mucosa (78.1%) and cystic fluctuation (56.3%) were not present showing no clinical alterations that might suggest cystic lesion. The most frequent clinical alteration was the color change of the crown (56.3%). The mean patient age at the time of traumatic injury was 2.7 years and the diagnosis of cyst at 5.9 years, and the mean time from trauma to diagnosis of cysts was 2.8 years. The hard tissue trauma occurred in 46.9% of teeth. Most injuries (59.3%) were of low severity. The radicular formation in the primary tooth involved in the lesion in 46.8% of cases was larger than its homologous and 62.5 % of cases the successor tooth germ of primary tooth with the cystic lesion was at a Nolla stage earlier than the homologous. The majority (81.2%) of cystic lesions did not involve adjacent teeth but promoted displacement of tooth germs in 56.2%. Repercussions in the permanent dentition were found in 31.3% of cases and prolonged retention of permanent in 15.6%. Given the findings, this study observed that the radicular cyst in traumatized primary incisors is rare. It assumes a less aggressive profile, controlled growth and requiring a long time to develop. Moreover, it seems to cause less harmful sequelae in dentitions, influence the process of root resorption and root formation and is associated with low severity trauma. The diagnosis must be made by radiographic findings. An external root resorption without bone formation, asymmetry in size between dental follicle (dental follicle of successor germ to the primary tooth involved with the cystic lesion and th homologous tooth follicle) and the difference in height and/or position between homologous teeth germs should also be considered amongst the radiographic signs in the diagnosis of radicular cysts.

Introduction: In 2007 Ontario implemented a grade 8 quadrivalent human papillomavirus (qHPV) vaccination program targeting the virus that causes cervical cancer. Despite being 6 years post-implementation, few post-licensure studies have assessed the safety of the qHPV vaccine in this adolescent population. Since autoimmune disorders are often targeted for post-marketing surveillance by regulatory agencies, it is important to assess the risk of developing an autoimmune disorder post-qHPV vaccination. Objectives: The objectives of this thesis were to assess the risk for developing an autoimmune disorder following qHPV vaccination, assess for effect modification by the presence of predisposing risk factors, identify the period of highest risk and explore the risk for individual autoimmune disorders. Methods: A population-based retrospective cohort of girls eligible for Ontario’s qHPV vaccination program was identified using population-based databases. The risk of autoimmune disorders following qHPV vaccination was ascertained using the self-controlled case series method. Results: The risk of developing a new autoimmune disorder, adjusted for age, seasonality, concurrent vaccines and infections was 1.28 (95% CI: 0.87 – 1.89), and this association was independent of a history of immune-mediated disorders (p=0.39). The risk was not increased during days 7-24 post-vaccination (adjusted RR = 0.87, 95% CI: 0.43 – 1.74), but appeared to increase thereafter (adjusted RR = 1.36, 95% CI: 0.77 – 2.41 and RR = 1.62, 95% CI 0.94 – 2.78 respectively, for days 25 – 42 and days 43 – 60), although these differences were non-significant. The risk may be increased for certain disorders including Bell’s palsy (RR = 2.30, 95% CI: 0.67 – 7.95), systemic autoimmune rheumatic disorders (RR = 1.84, 95% CI: 0.42 – 8.02), Hashimoto’s disease (RR = 1.39, 95% CI: 0.46 – 4.22), and juvenile rheumatoid arthritis (RR = 1.31, 95% CI: 0.83 – 2.08), although none of these associations were statistically significant. Conclusion: This thesis demonstrated that no statistically significant increased risk for autoimmune disorders following qHPV vaccination was detected. However, there remains some uncertainty about the safety of the qHPV vaccine for a subset of the autoimmune disorders. The results from this analysis need to be pooled with those of other studies to confirm whether these are true safety signals. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2014-04-23 22:30:41.428

Este estudo buscou verificar a ocorrência de casos de cisto radicular em incisivos superiores decíduos traumatizados e descrever suas características relacionadas à criança, ao dente, ao trauma e ao cisto. Para tanto, realizou-se um levantamento das informações clínicas e radiográficas, de 2498 prontuários de pacientes atendidos na Clínica do Centro de Pesquisa e Atendimento de Traumatismo de Dentes Decíduos da Disciplina de Odontopediatria da FOUSP, no período de 1998 a setembro de 2013. Foi utilizado o método exploratório descritivo de uma série de casos. Foram avaliados 30 prontuários com casos de cistos, totalizando 32 incisivos superiores decíduos traumatizados com cisto. A ocorrência de cisto em pacientes com incisivos superiores decíduos traumatizados foi de 1,2%. Os resultados mostraram que a maioria dos cistos acometeram o gênero feminino (59,4%), os incisivos centrais superiores decíduos (93,8%), em crianças maiores de 5 anos (81,2%), mas que sofreram traumatismos com menos de 4 anos de idade (81,2%). A maioria dos casos não apresentou alteração clínica que levasse a suspeita de lesão cística, pois não foi encontrado em 90,7% retração gengival, 65,6% alteração de cor da mucosa vestibular, 65,6% fistula, 75% abscesso, 56,2% abaulamento gengival, 78,1% depressão da mucosa vestibular e 56,3% flutuação cistíca. A alteração clínica mais frequente foi a alteração de cor da coroa (56,3%). A média da idade do paciente no momento do trauma foi de 2,7 anos e do diagnóstico do cisto de 5,9 anos, sendo que a média de tempo do trauma até o diagnóstico do cisto foi de 2,8 anos. Em 46,9% dos dentes ocorreu trauma dental. A maioria dos traumas foram de baixa severidade (59,3%). Em 46,8% dos casos, o dente decíduo envolvido na lesão apresentava maior formação radicular que seu homólogo e em 62,5% o germe sucessor do dente decíduo com a lesão cística encontrava-se em estágio de Nolla anterior que o homólogo. A maioria das lesões císticas (81,2%) não envolveu dentes adjacentes, mas promoveram deslocamento de germes em 56,2%. Na dentição permanente foram encontrados repercussões em 31,3,% dos casos e retenção prolongada do permanente em 15,6%. Diante dos achados deste estudo observou-se que o cisto radicular em incisivos decíduos traumatizados é raro, assume um perfil menos agressivo, de crescimento controlado e necessitando de um tempo longo para se desenvolver. Além do mais, parece causar sequelas menos danosas às dentições, influenciar no processo de rizólise e rizogênese e estar relacionado a traumas de baixa severidade. O diagnóstico deve ser realizado pelos achados radiográficos, sendo que a reabsorção radicular externa sem formação óssea, assimetria no tamanho do folículo do germe dentário sucessor ao dente envolvido com a lesão cística e o folículo homólogo, bem como a diferença de altura e/ou posição entre os germes dentários homólogos deveriam ser considerados como sinais radiográficos no diagnóstico de cistos radiculares. / The present study aimed to verify the occurrence of radicular cyst in traumatized primary upper incisors and describe their characteristics in relation to the children, teeth, trauma and cysts. The survey of 2, 498 patients that presented and were treated at the Research and Clinical Center of Dental Trauma in Primary Teeth of the School of Dentistry of the University of Sao Paulo from 1998 to September 2013 was carried out, in order to collect clinical and radiographic information. A descriptive and exploratory approach was taken in the study. A total of thirty clinical records involving radicular cysts included thirty two traumatized primary upper incisors were studied in detail. The overall occurrence of cysts in patients with traumatized primary incisors was 1.2% with females affected more (59.4%) often than males 93.8% involved the upper central incisors. 81.2% of the children were older than 5 year of age but suffered traumatic injuries before 4 years old. In most cases, gingival recession (90.7%); color change of the vestibular mucosa (65.6%); fistula (65.6%); abscess (75%); gingival bulging (56.2%); depression of the vestibular mucosa (78.1%) and cystic fluctuation (56.3%) were not present showing no clinical alterations that might suggest cystic lesion. The most frequent clinical alteration was the color change of the crown (56.3%). The mean patient age at the time of traumatic injury was 2.7 years and the diagnosis of cyst at 5.9 years, and the mean time from trauma to diagnosis of cysts was 2.8 years. The hard tissue trauma occurred in 46.9% of teeth. Most injuries (59.3%) were of low severity. The radicular formation in the primary tooth involved in the lesion in 46.8% of cases was larger than its homologous and 62.5 % of cases the successor tooth germ of primary tooth with the cystic lesion was at a Nolla stage earlier than the homologous. The majority (81.2%) of cystic lesions did not involve adjacent teeth but promoted displacement of tooth germs in 56.2%. Repercussions in the permanent dentition were found in 31.3% of cases and prolonged retention of permanent in 15.6%. Given the findings, this study observed that the radicular cyst in traumatized primary incisors is rare. It assumes a less aggressive profile, controlled growth and requiring a long time to develop. Moreover, it seems to cause less harmful sequelae in dentitions, influence the process of root resorption and root formation and is associated with low severity trauma. The diagnosis must be made by radiographic findings. An external root resorption without bone formation, asymmetry in size between dental follicle (dental follicle of successor germ to the primary tooth involved with the cystic lesion and th homologous tooth follicle) and the difference in height and/or position between homologous teeth germs should also be considered amongst the radiographic signs in the diagnosis of radicular cysts.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13376号 / 論医博第2210号 / 新制||医||1047(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 森田 智視, 教授 川上 浩司, 教授 佐藤 俊哉 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Clinical observations of individual patients are the cornerstones for furthering our understanding of the human body, diseases, and therapeutics. Traditionally, clinical observations were communicated through publishing case reports and case series. The effort of identifying and investigating unusual clinical observations has always rested on the shoulders of busy clinicians. To date, there has been little effort dedicated to increasing the efficiency of identifying unique and uncommon patient observations that may lead to valuable discoveries. In this thesis, we propose and implement an augmented intelligence framework to identify potential novel clinical observations by combining machine analytics through outlier analysis with the judgment of subject-matter experts. Preeclampsia is a significant cause of maternal and perinatal mortality and morbidity, and advances in its management have been slow. Considering the complex etiological nature of preeclampsia, clinical observations are essential in advancing our understanding of the disease and therapeutic approaches. Thus, the objectives and studies in this thesis aim to answer the hypothesis that using outlier analysis in preeclampsia-related medical data would lead to identifying previously uninvestigated clinical cases with new clinical insight. This thesis combines three articles published or submitted for publication in peer-reviewed journals. The first article (published) is a systematic review examining the extent to which case reports and case series in preeclampsia have contributed new knowledge or discoveries. We report that under one-third of the identified case reports and case series presented new knowledge. In our second article (submitted for publication), we provide an overview of outlier analysis and introduce the framework of augmented intelligence using our proposed extreme misclassification contextual outlier analysis approach. Furthermore, we conduct a systematic review of obstetrics-related research that used outlier analysis to answer scientific questions. Our systematic review findings indicate that such use is in its infancy. In our third article (published), we implement the proposed augmented intelligence framework using two different outlier analysis methods on two independent datasets from separate studies in preeclampsia and hypertensive disorders of pregnancy. We identify several clinical observations as potential novelties, thus supporting the feasibility and applicability of outlier analysis to accelerate clinical discovery.

Deux articles ont été publiés suite à ce mémoire de maîtrise. Un prix pour la meilleure affiche faite par un étudiant du département de psychiatrie de l'Universtité de Montréal a été obtenu suite à la présentation de résultats préliminaires à la Journée annuelle du Centre de recherche de l’Institut Universitaire en santé mentale de Montréal. Un support financier et des bourses ont été également accordés. Par exemple: Bourse d’excellence pour la recherche en psychiatrie, bourse du Cinquantenaire, Faculté de médecine, Département de psychiatrie, Université de Montréal; Bourse d’excellence du directeur de recherche, Centre d’études sur les troubles obsessionnels compulsifs et les tics- CETOCT; Centre recherche de l’Institut universitaire en santé mentale de Montréal; Bourse de Dépannage de la Faculté de médecine ainsi qu'une bourse de rédaction, Faculté de médecine de l’Université de Montréal, Montréal (QC). / Les troubles anxieux représentent les problèmes de santé mentale les plus répandus. Ils affectent 12% de la population, causent un handicap léger à grave et peuvent représenter un lourd fardeau pour les patients et leurs proches. Ils entrainent un impact économique majeur pour la société en termes d’utilisation accrue des services de santé tant psychiatriques que non psychiatriques, de diminution de productivité au travail, d’absentéisme et du chômage. Cette étude de type série de cas, décrit une stratégie d’augmentation ou de facilitation du changement en psychothérapie basée sur l’amorçage (priming) préconscient et son utilisation dans le traitement de huit patients souffrant de troubles anxieux. Les patients avaient manifesté une réponse symptomatique partielle à la thérapie cognitive-comportementale (TCC) malgré une bonne adhésion au traitement. La démarche d’augmentation de la psychothérapie par amorçage préconscient (APAP) comporte six étapes permettant d’établir des formulations cognitives adaptées à la problématique résiduelle personnelle du patient. Ces formulations sont enregistrées et masquées par une musique relaxante. Les patients ont écouté cet enregistrement dans un état d’inattention pendant 20 minutes deux fois par jour durant huit semaines. L’effet de cette stratégie a été évalué par des mesures de type quantitatif et qualitatif, des mesures auto rapportées par les patients par rapport aux changements cognitifs idiosyncratiques ainsi que par un questionnaire sur la qualité de vie. Les résultats élaborés par une analyse descriptive incluant une exploration de la signification statistique et clinique des effets observés montrent, que la stratégie d’amorçage préconscient est associée à des changements cognitifs favorables, à une diminution du discours intérieur négatif et problématique chez sept patients sur huit. Ces bienfaits ont été également maintenus à la 24ème semaine. Une nette amélioration clinique des symptômes anxieux et du fonctionnement global a été observée chez deux patients qui souffraient uniquement d’un trouble anxieux versus les six autres qui présentent une comorbidité additionnelle à leur diagnostic primaire. Ces derniers ont quand même vu une amélioration de leur qualité de vie comparativement à leur état avant de recevoir la stratégie APAP. L’émergence de pensées et d’attitudes positives et la diminution des pensées dysfonctionnelles observées chez la majorité des patients à la suite du traitement par APAP, suggère un impact favorable de l’intervention. La démarche APAP qui est accessible par Internet pourrait constituer un ajout au traitement par TCC en facilitant ou en augmentant le changement cognitif et symptomatique. / Anxiety disorders represent some of the most common mental health problems. These disorders affect up to 12% of the population causing mild to severe impairment and a potentially heavy burden for patients and their families. In addition, these disorders have a major economic impact on society in terms of increased use of health services both psychiatric and non- psychiatric, lower work productivity, absenteeism and unemployment. The current paper is a case series describing a new method for facilitating change based on Psychotherapy Augmentation through Preconscious Priming (APAP) and its use in the treatment of eight patients suffering from an anxiety disorder. Previously, the patients had shown only a partial response to CBT despite good adherence to treatment. Following this treatment, the patients completed the APAP process, which consisted of six steps during which alternative, more functional thoughts and beliefs were formulated, relevant to the idiosyncratic difficulties experienced by the patients. Subsequently, these formulations were recorded and mixed with masking relaxing music, following which the patient listened to the recordings in a passive state twice daily for 20 minutes for a period of 8 weeks. The effect of this strategy was evaluated by quantitative and qualitative measures administered before treatment with the APAP program, at 8 weeks, 16 weeks and 24 weeks. In addition, idiosyncratic ratings of dysfunctional thoughts, symptoms of anxiety, global functioning and quality of life were assessed at baseline and at 24 weeks. Results showed a significant reduction in dysfunctional thoughts reported by most patients treated with this method. There was substantial clinical improvement in anxiety symptoms both for patients who presented with and without co-morbid psychological disorders. Those with co-morbid psychological disorders who did not have a good quality of life at the start of treatment reported an increase in quality of life following treatment with APAP. In addition, a descriptive analysis of the results supported the notion that a preconscious priming strategy is associated with positive cognitive change with a reduction in negative thoughts in 7 out of 8 patients, which were maintained in the longer term. Further, this descriptive analysis suggested that patients who suffered from an anxiety disorder without co-morbidity showed more clinically significant improvement in anxiety symptoms and improved global functioning in comparison to those who presented with a co-morbid disorder. Overall, results suggested that the APAP intervention had a positive impact on the patients. Results showed that APAP led to positive cognitive changes in all patients and clinically significant improvement in anxiety symptoms and global functioning in patients without additional comorbidities. APAP could be a valuable addition to CBT by facilitating or enhancing cognitive and symptom change.