Each year approximately five million people are treated in the nation's intensive care units making intensive care one of the most expensive components of the U.S. healthcare system. Of these patients, 400,000-500,000 will die annually giving the ICU the distinction of having the highest rate of mortality and complications in the hospital setting. Studies have demonstrated that one in ten patients who die each day in ICUs might survive if intensivists were present to manage clinical care and direct treatment plans (Randolph & Pronovost, 2002; Dimick, Pronovost, Heitmiller & Lipsett, 2001; Pronovost et al., 2002). The utilization of supplemental remote telemedicine has been investigated as a means of compensating for the limited resource of intensivists (Breslow et al., 2004; Rosenfeld et al., 2000). One specific use of this technology, the electronic intensive care unit or eICU®, has previously demonstrated the potential to improve physiological and economic outcomes in ICU patients through the use of integrated decision-support and patient data systems. The present study focuses on the eICU® as a 21st century technology capable of improving the quality of patient care and identifies those factors most likely to impact the success of this clinical intervention. This research utilizes a non-experimental pre-and post-intervention study design and examines patient data collected on all admissions to five ICUs managed by two regional tertiary care hospitals during a 36-month time period. Each ICU is equipped with eICU® software systems that allow intensivist surveillance of patients from a remote facility. The data is analyzed using both structural equation modeling and decision tree regression modeling to statistically evaluate the effects of patient, hospital and unit characteristics on proximal and distal outcomes in ICU patients. As the development of clinical complications subsequently affects patient length of stay, cost of stay, and mortality, it becomes increasingly imperative to seek interventions capable of reducing the risk of unfavorable patient outcomes. This study closely examines one such intervention, the eICU®.

No description available.

No description available.

Background: Coronary artery disease is a common cause of morbidity and mortality in the UK. Interventional revascularisation procedures for addressing the disease include percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), which respectively seek to open up or bypass blocked arteries to restore blood flow to heart muscle. Rates at which these procedures are carried out have changed in recent years, as have clinical indications for referral. PCI is delivered by interventional cardiologists, while CABG is carried out by cardiothoracic surgeons, necessitating multi-disciplinary decision making. There is both within- and cross-speciality debate as to the optimal treatment strategy in some case types. Evaluation of the care provided is of clinical and political importance, and requires information about how post-procedure event rates per operator and hospital compare with those expected given the composition of patient populations. Methods: Two UK-wide audit databases of PCI and CABG procedures were used to explore a range of clinical outcome questions. The patient populations contained within each database were compared to see how they differed, and also how each had changed in recent years. In CABG patients, comparative effectiveness of two different surgical techniques (single vs bilateral mammary artery grafting) was assessed with respect to both short-term and long-term mortality outcomes. In PCI patients, a risk model to predict 30-day mortality was developed for use in clinical appraisal. Results: In both patient populations there had been changes to the relative frequencies of many characteristics over time. In the CABG population, multivariable analysis showed that patients undergoing single mammary artery grafting had lower odds of all-cause mortality within 30 days of procedure than those receiving bilateral mammary artery grafting, but had worse overall survival in the long term. In the PCI population, the developed risk model demonstrated good calibration and discrimination at predicting 30-day all-cause mortality. Discussion: The studies described above demonstrate that large-scale routinely collected data can be used to gain insights into clinical care quality and delivery. These resources are under-utilised at present; correcting this requires an understanding of the limitations of the data and how the information contained therein relates to actual clinical care.

Introduction: Few studies have investigated the nature and prevalence of drug therapy problems (DTPs) in women's health settings, which may compromise safe care for these patients. Objective: This study was to identify risk factors and clinical outcomes for the development of drug therapy problems in the puerperium of patients with gestational hypertension. Methods: A case-control study and a prospective cohort was performed with puerperae diagnosed with gestational hypertension in two Brazilian maternity schools between june and november 2016. Patients with at least one DTP were allocated as case, whereas patients without DTPs were allocated as control. Results: 600 women were included in the study: 354 in the case group, 246 in the control group. The main risk factors for DTPs were increased number of drugs during hospitalization (p = 0.000), lower gestational age at delivery (p = 0.032) and the first gestation (p = 0.016). Of the 354 (59%) patients who had at least one DTP, 244 (68.9%) had one DTP, 98 (27.7%) had two DTPs. The main types of DTPs were: (1) non-administration of the prescribed drug, (2) nonprescription of a drug despite clear indication and (3) failure of therapy (ineffectiveness). The drugs most associated with DTPs were methyldopa 83 (17.2%), ferrous sulfate 318 (66.5%), dipyrone 24 (5%). In addition to methyldopa, other antihypertensive drugs, such as nifedipine, captopril, losartan, were also involved in DTPs, but in less than 5% of patients. In patients exposed to DTPs, the length of hospital stay was 5.45 (SD 3.60) days versus 4.48 (SD 3.32) days in patients not exposed to DTPs (p = 0.001). The time (in days) to achieve BP control was 4.49 (3.58) and 3.47 (3.26), respectively (p = 0.000). There were no deaths. Conclusion: Drug therapy related problems are common events during the postpartum period of patients with gestational hypertension. The three risk factors identified in this study should be considered in the future in the risk analysis of hospitalized puerperae, and suggest levels of alertness for the management of pharmacotherapy in this group of patients. The presence of these events significantly increases the postpartum period of permanence and the time to normalize blood pressure. / Introdução: Poucos estudos têm investigado a natureza e prevalência de problemas farmacoterapêuticos (PFTs) em ambientes de saúde da mulher, o que pode comprometer a assistência segura a essas pacientes. Objetivo: identificar os fatores de risco e os desfechos clínicos para o desenvolvimento de problemas farmacoterapêuticos no puerpério de pacientes com hipertensão na gestação. Método: Foi realizado um estudo de caso-controle e uma coorte prospectiva com puérperas diagnosticadas com hipertensão na gestação em duas maternidadesescola do Brasil, de junho a novembro de 2016. Pacientes com ao menos um problema farmacoterapêutico foram elegíveis como intervenção, enquanto pacientes sem problemas farmacoterapêuticos foram elegíveis como controle. Resultados: 600 mulheres foram incluídas no estudo: 354 no grupo caso e 246 no grupo controle. Os principais fatores de risco para problemas farmacoterapêuticos foram o aumento do número de medicamentos durante a internação (p=0,000), a menor idade gestacional no momento do parto (p=0,032) e a paciente estar na primeira gestação (p=0,016). Das 354 (59%) pacientes que apresentaram pelo menos um problema farmacoterapêutico, 244 (68,9%) tiveram um problema farmacoterapêutico, 98 (27,7%) tiveram dois problemas farmacoterapêuticos. Os principais tipos de problemas farmacoterapêuticos foram: (1) não administração do medicamento prescrito, (2) não prescrição de um medicamento apesar de indicação clara e (3) falha terapêutica (inefetividade). Os medicamentos mais associados a problemas farmacoterapêuticos foram a metildopa 83 (17,2%), sulfato ferroso 318 (66,5%), dipirona 24 (5%). Além da metildopa, outros medicamentos anti-hipertensivos, como nifedipino, captopril, losartana, também estiveram envolvidos em problemas farmacoterapêuticos, porém em menos 5% das pacientes. Em doentes expostos a problemas farmacoterapêuticos, o tempo de internação foi de 5,45 (DP 3,60) dias versus 4,48 (DP 3,32) dias em doentes não expostos a problemas farmacoterapêuticos (p = 0,001). O tempo (em dias) para alcançar o controle da pressão arterial foi de 4,49 (3,58) e 3,47 (3,26), respectivamente (p = 0,000). Não houve mortes. Conclusão: Os problemas farmacoterapêuticos são eventos comuns durante o período pós-parto de pacientes com hipertensão gestacional os três fatores de risco identificados neste estudo devem ser considerados futuramente na análise de risco de puérperas hospitalizadas, e sugerem níveis de alerta para o manejo da farmacoterapia neste grupo de pacientes. A presença destes eventos aumenta significativamente o período pós-parto de permanência e o tempo de normalização da pressão arterial.

L’insuffisance cardiaque (IC) est associée à une mortalité élevée et de récurrentes hospitalisations. Sa détection précoce et sa prise en charge sont alors considérées fondamentales à une amélioration de la survie et de la qualité de vie des patients qui en souffrent. Pourtant, bien que des lignes directrices synthétisant les évidences des essais cliniques phares soient périodiquement publiées pour guider les cliniciens dans la prise en charge de l’IC, l’adhésion des professionnels de la santé à celles-ci semble être insatisfaisante. En effet, alors que les taux de prescription de certaines thérapies soient élevés, les doses prescrites n’atteignent pas toujours les cibles recommandées et d’autres thérapies sont moins utilisées. Ainsi, bien que l’inertie clinique puisse justifier une partie de ces lacunes, une caractérisation plus élaborée de cette adhésion aux lignes directrices en milieu clinique est nécessaire à une meilleure compréhension de ces écarts et par le fait même, à une meilleure prise en charge de l’IC. L’objectif de ce projet est alors de dresser, dans un premier temps, un portrait détaillé de la prise en charge des patients atteints d’IC avec une fraction d’éjection réduite suivis par une équipe interdisciplinaire dans une clinique ambulatoire spécialisée au Québec puis, dans un second temps, d’évaluer l’impact de cette adhésion sur le pronostic de ces patients. Le premier papier présenté dans ce travail démontre non seulement des taux de prescriptions élevés, mais également des taux d’optimisation des thérapies recommandées supérieurs à ce qui est rapporté dans la littérature, lorsque les paramètres physiologiques et biologiques propres à chaque patient sont considérés. Il reste néanmoins une proportion considérable de patients qui nécessitent une titration plus lente au-delà des 6 mois recommandés tandis que d’autres demeurent indéfiniment à des doses inappropriées. Le second papier présenté approfondit cette analyse et démontre que les patients recevant un traitement pharmacologique aux doses optimales sont ceux qui présentent le meilleur pronostic dans l’année suivant la période d’optimisation allouée, suivis de ceux nécessitant une titration prolongée puis, ceux demeurant à des doses sous-optimales. Or, les patients à plus haut risque de morbidité ou de mortalité sont ceux présentant une intolérance ou une contre-indication aux thérapies recommandées, une population de patients fragiles nécessitant une attention particulière lors de la prise en charge de leur IC. / Heart failure (HF) is associated with high mortality rates and recurrent hospitalizations. Hence, its early detection and optimal management are essential to improve the survival and quality of life of patients who suffer from it. Yet, although guidelines synthesizing evidence from landmark clinical trials are periodically published to guide clinicians regarding the management of HF, healthcare providers’ adherence to these recommendations appears to be unsatisfactory. Indeed, while the prescription rates for some therapies are high, doses prescribed do not always reach recommended targets, let alone other therapies that are less often used. Although clinical inertia has been suggested to potentially justify some of these care gaps, a more elaborate characterization of this adherence to guidelines in the real-world clinical setting is necessary for a better understanding of these deviations and ultimately, for a better management of HF. The objective of this project is therefore to, firstly, draw-up a detailed portrait of the management of patients with HF and reduced ejection fraction (HFrEF) followed by a multidisciplinary team in a specialized outpatient clinic in Quebec and then, to assess the impact of the different level of adherence to guidelines on the prognosis of these patients. The first paper presented in this work demonstrates not only high prescription rates, but also rates of optimization of recommended therapies higher than what was previously reported in the literature, when physiological and biological parameters specific to each patient are considered. However, there remains a considerable proportion of patients who require slower titration beyond the recommended 6 months while others remain indefinitely on inappropriately low doses. The second paper presented deepens this analysis and demonstrates that patients receiving pharmacological treatment at optimal doses are those with the best prognosis in the year following the allocated optimization period, followed by those requiring prolonged titration and then those remaining at suboptimal doses. However, the patients at the highest risk of morbidity or mortality are those presenting an intolerance or a contraindication to the recommended therapies, a population of fragile patients requiring special attention during the management of their HF.

Introduction et objectifs : La survenue d'une lésion médullaire (LM) causant une tétraplégie est un évènement tragique entraînant des conséquences dévastatrices sur la vie des individus et des coûts faramineux pour notre système de santé. Les individus qui subissent une LM traumatique avec tétraplégie nécessitent en général plusieurs semaines d’hospitalisation en centre de soins aigus où ils seront particulièrement à risque de complications médicales. Alors que des facteurs reliés au traumatisme initial ou au patient sont reconnus pour déterminer leur évolution clinique, l’impact de la gestion péri-opératoire suivant une LM parmi ces facteurs est encore imprécis. Ainsi, l’objectif principal de ce travail est d’identifier les facteurs influençant le déroulement de la phase d’hospitalisation aigue, en terme d’évolution clinique et d’utilisation de ressources hospitalières, suivant une tétraplégie aigue. Ensuite, afin de déterminer leur pertinence clinique à long terme, le second objectif de ce projet consiste à déterminer si ceux-ci ont également un impact sur la récupération fonctionnelle six mois post lésion. Méthodologie et résultats : Une étude rétrospective basée sur une banque de données prospective collectée dans un centre de traumatologie tertiaire, ainsi qu’une étude prospective prédictive ont été complétées. En plus de différents facteurs sociodémographiques et reliés au traumatisme initial (non-modifiables), une admission précoce en centre de soins spécialisés et la diminution de la survenue de complications représente des facteurs importants modifiables qui améliorent l’évolution clinique et l’utilisation de ressources en phase d’hospitalisation aigue. Une gestion chirurgicale et péri-opératoire spécialisée dans un centre pour LM influence significativement le cours de l’hospitalisation aigue en améliorant différents paramètres cliniques, de même qu’en diminuant les coûts et la durée de séjour en soins aigus chez les patients tétraplégiques. La survenue de complications médicales et l’augmentation du délai de séjour en soins aigus sont des facteurs prédictifs de récupération fonctionnelle sous-optimale six mois post-lésion. Conclusions: Le déroulement de l’hospitalisation aigue peut influencer l’évolution clinique des patients tétraplégiques et l’utilisation des ressources de notre système de santé. Mais également, le déroulement de l’hospitalisation peut avoir un impact significatif sur la récupération fonctionnelle plus de six mois post lésion. Une gestion péri-opératoire et chirurgicale précoce en centres de soins spécialisés en LM est fortement suggérée suivant une tétraplégie traumatique aigue, afin d’optimiser l’évolution clinique et le transfert des patients en réadaptation fonctionnelle intensive pour ainsi optimiser leur récupération fonctionnelle. Ceci pourrait également significativement diminuer la charge économique sur notre système de santé. Retombées : En soulevant l’importance d’une gestion optimale en soins aigus, cette étude permet d’appuyer les recommandations actuelles, de faible niveau, suggérant le transfert rapide de patients avec LM en centre spécialisés. Une gestion hospitalière aigue centrée vers la prévention des complications médicales et la récupération neuro-fonctionnelle doit être mise en place le plus tôt possible suivant une LM et particulièrement suivant une tétraplégie. Ce travail permettra ainsi de justifier l’élaboration de projets subséquents qui permettront d’élaborer des protocoles de gestion clinique et administratif plus précis, pour mieux encadrer et définir l’importance des centres de soins aigus spécialisés, et pour favoriser le transfert de connaissances en centres non spécialisés. / Introduction and objectives: The occurrence of a spinal cord injury (SCI) causing tetraplegia is a tragic event leading to devastating consequences on the life of individuals and huge costs to our healthcare system. Individuals who experience a traumatic SCI (TSCI) with tetraplegia require several weeks of hospitalisation in an acute care center where they are at risk of various medical complications. While factors related to the initial trauma or to the patient’s baseline characteristics are recognized to determine their clinical outcome, the impact of the perioperative management following a TSCI is still unclear. Thus, the main objective of this study is to identify factors influencing the course of acute care hospitalization in terms of clinical outcome and use of hospital resources following acute tetraplegia. Then, in order to determine clinical relevance of these factors in longer-term outcome of patients, the second objective of this project is to determine if these factors also have an impact on the functional recovery six months post injury. Methods and results: A retrospective cohort study in a single level-1 trauma center specialized in SCI care, and a predictive prospective study were completed. Early admission to a specialized SCI center and a decreased incidence of medical complications during acute care hospitalization were found to significantly improve clinical outcomes and decrease resource utilization during acute care. Higher occurrence of medical complications and longer acute care length of stay were significant predictors of lower functional recovery (as measured by the Spinal Cord Independence Measure six-months post injury). Conclusions: Optimization of acute care hospitalization in a specialized center may improve clinical outcomes and decrease hospital resource utilization following acute tetraplegia and thereby have a positive impact on the 6-month functional recovery. Early admission and complete perioperative management in a specialized SCI center is thus recommended following tetraplegia. This could also reduce the economic burden on our healthcare system. Clinical applications and future directions: By highlighting the importance of high-quality care following acute SCI, this study supports current recommendations suggesting prompt transfer to a specialized acute care center following tetraplegia. Acute care management focussing on the early prevention of medical complications and optimization of recovery should be provided as early as possible following tetraplegia. Future projects working towards development of precise clinical and administrative protocols for acute SCI care will help to better regulate and define the importance of specialized centers, and to promote knowledge transfer.

INTRODUÇÃO: A análise de eventos clínicos em um ensaio randomizado estabelece a eficácia e segurança de um novo tratamento. Os eventos clínicos são divididos em eventos adversos (EAs) e desfechos clínicos. A literatura é escassa em informações sobre o processo de coleta de eventos clínicos em estudos, bem como sobre a variabilidade entre os centros de pesquisa em reportar eventos clínicos. OBJETIVOS: Descrever todos os eventos clínicos (EAs e desfechos clínicos) reportados pelos centros participantes do estudo APPRAISE-2 (Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome) e caracterizar a sua seriedade. Avaliar a variabilidade entre os centros de pesquisa em reportar eventos clínicos, além de identificar características basais dos participantes associadas ao ato de reportar eventos. MÉTODOS: Os investigadores clínicos foram responsáveis por reportar todos os eventos apresentados pelos participantes em formulários específicos. Formulários para EAs e para cada um dos desfechos clínicos do estudo foram disponibilizados (infarto agudo do miocárdio ou angina instável, acidente vascular encefálico e sangramento). Suspeitas de desfechos clínicos foram enviadas ao comitê de classificação de eventos clínicos (CEC), que as validou de acordo com critérios pré-estabelecidos. Tanto os desfechos clínicos quanto os EAs foram classificados como \"sérios\" ou \"não-sérios\" pelos investigadores clínicos. Para avaliar a variabilidade em reportar eventos clínicos, somente centros com inclusão de >= 10 participantes foram considerados. Modelos estatísticos foram utilizados para avaliar a influência de região geográfica e de características dos participantes na variabilidade entre os centros em reportar eventos. Os dados coletados estão concentrados no Instituto de Pesquisa Clínica da Universidade de Duke, na Carolina do Norte, Estados Unidos. RESULTADOS: Um total de 13.909 eventos clínicos foram reportados por 858 centros de pesquisa em 39 países. A maioria desses eventos foram EAs (91,6%), sendo os demais desfechos clínicos. Dentre os desfechos clínicos reportados, 66,0% foram confirmados pelo CEC. A maior parte dos desfechos confirmados pelo CEC (94,0%) preencheu critérios de seriedade, enquanto que 63,2% dos desfechos negados pelo CEC foram considerados sérios. De todos os EAs, 17,9% foram sérios. O critério de seriedade mais comumente observado foi hospitalização (N=2594), seguido de morte (N=321). Um ajuste para região geográfica explicou 28,7% e 26,4% da variabilidade entre os centros em reportar desfechos clínicos e EA sérios, respectivamente; a adição de características dos participantes ao modelo explicou mais 25,4% da variabilidade entre os centros em reportar desfechos clínicos e 13,4% em reportar EAs sérios. Os ajustes promoveram pouco impacto em explicar a variabilidade em reportar EAs não-sérios. Diversas características clínicas foram associadas ao ato de reportar eventos clínicos. CONCLUSÃO: Em um ensaio clínico multicêntrico de fase III, a maioria dos eventos clínicos reportados foram EAs não-sérios. Região geográfica e características dos pacientes influenciaram a variabilidade entre os centros em reportar desfechos clínicos e EAs sérios, com pouco impacto em EAs não-sérios. Uma coleta integrada de desfechos clínicos e EAs é viável, informativa e ilustra as características que estes eventos compartilham / BACKGROUND: The collection of adverse events (AEs) and clinical endpoints determines the overall efficacy and safety of the study treatment in clinical trials. However, AEs and clinical endpoints are captured and processed separately with limited information on various aspects of this data collection, its integration, and its variation across sites. OBJECTIVES: To describe all site-reported clinical events in the APPRAISE-2 (Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome) trial and report their seriousness. To evaluate the variability in reporting clinical events across sites and identify characteristics associated with clinical event reporting. METHODS: All clinical events were collected in case report forms (CRF) by site-investigators, as AEs or suspected endpoints. Data on suspected endpoints were collected in specific CRFs (myocardial infarction or unstable angina, cerebrovascular event and bleeding) and sent to review by a clinical events committee (CEC) that adjudicated these events according to predefined criteria. Seriousness criteria was collected for all AEs and suspected endpoints. To explore site-level variability i n event reporting, sites with >=10 participants were i ncluded. Statistical models explored the influence of geographic region and patient characteristics in between-site variability in event reporting. All collected data is centered in the Duke Clinical Research Institute, North Carolina, Unites States. RESULTS: A total of 13.909 clinical events were reported by 858 sites in 39 countries. Most clinical events were AEs (91.6%), followed by suspected endpoints. Of suspected endpoints reviewed by CEC, 66.0% were confirmed. Most CEC-confirmed endpoints met serious criteria (94.0%) and, of CEC-negatively adjudicated endpoints, 63.4% were serious. Of all AEs, 17.9% were considered serious events. Hospitalization was the most common criterion for classification as serious event (N=2594), followed by death (N=321). In models accounting for geographic region, site variation in reporting endpoints and serious AEs was explained by 28.7% and 26.4%, respectively; adding patient characteristics further explained site variation by 25.4% for endpoint reporting and 13.4% for serious AE reporting. Non-serious AE reporting variation was not explained by patient characteristics or region. Several clinical characteristics were associated with clinical event reporting. CONCLUSION: In a multicenter phase III clinical trial, the majority of reported events were non-serious AEs. Geographic region and patient characteristics influenced between-site variability in reporting of clinical endpoints and serious AEs, with limited impact in non-serious AEs. An integrated collection of endpoints and AEs is feasible, possible in a multinational trial and illustrates the shared characteristics of events

INTRODUÇÃO: A análise de eventos clínicos em um ensaio randomizado estabelece a eficácia e segurança de um novo tratamento. Os eventos clínicos são divididos em eventos adversos (EAs) e desfechos clínicos. A literatura é escassa em informações sobre o processo de coleta de eventos clínicos em estudos, bem como sobre a variabilidade entre os centros de pesquisa em reportar eventos clínicos. OBJETIVOS: Descrever todos os eventos clínicos (EAs e desfechos clínicos) reportados pelos centros participantes do estudo APPRAISE-2 (Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome) e caracterizar a sua seriedade. Avaliar a variabilidade entre os centros de pesquisa em reportar eventos clínicos, além de identificar características basais dos participantes associadas ao ato de reportar eventos. MÉTODOS: Os investigadores clínicos foram responsáveis por reportar todos os eventos apresentados pelos participantes em formulários específicos. Formulários para EAs e para cada um dos desfechos clínicos do estudo foram disponibilizados (infarto agudo do miocárdio ou angina instável, acidente vascular encefálico e sangramento). Suspeitas de desfechos clínicos foram enviadas ao comitê de classificação de eventos clínicos (CEC), que as validou de acordo com critérios pré-estabelecidos. Tanto os desfechos clínicos quanto os EAs foram classificados como \"sérios\" ou \"não-sérios\" pelos investigadores clínicos. Para avaliar a variabilidade em reportar eventos clínicos, somente centros com inclusão de >= 10 participantes foram considerados. Modelos estatísticos foram utilizados para avaliar a influência de região geográfica e de características dos participantes na variabilidade entre os centros em reportar eventos. Os dados coletados estão concentrados no Instituto de Pesquisa Clínica da Universidade de Duke, na Carolina do Norte, Estados Unidos. RESULTADOS: Um total de 13.909 eventos clínicos foram reportados por 858 centros de pesquisa em 39 países. A maioria desses eventos foram EAs (91,6%), sendo os demais desfechos clínicos. Dentre os desfechos clínicos reportados, 66,0% foram confirmados pelo CEC. A maior parte dos desfechos confirmados pelo CEC (94,0%) preencheu critérios de seriedade, enquanto que 63,2% dos desfechos negados pelo CEC foram considerados sérios. De todos os EAs, 17,9% foram sérios. O critério de seriedade mais comumente observado foi hospitalização (N=2594), seguido de morte (N=321). Um ajuste para região geográfica explicou 28,7% e 26,4% da variabilidade entre os centros em reportar desfechos clínicos e EA sérios, respectivamente; a adição de características dos participantes ao modelo explicou mais 25,4% da variabilidade entre os centros em reportar desfechos clínicos e 13,4% em reportar EAs sérios. Os ajustes promoveram pouco impacto em explicar a variabilidade em reportar EAs não-sérios. Diversas características clínicas foram associadas ao ato de reportar eventos clínicos. CONCLUSÃO: Em um ensaio clínico multicêntrico de fase III, a maioria dos eventos clínicos reportados foram EAs não-sérios. Região geográfica e características dos pacientes influenciaram a variabilidade entre os centros em reportar desfechos clínicos e EAs sérios, com pouco impacto em EAs não-sérios. Uma coleta integrada de desfechos clínicos e EAs é viável, informativa e ilustra as características que estes eventos compartilham / BACKGROUND: The collection of adverse events (AEs) and clinical endpoints determines the overall efficacy and safety of the study treatment in clinical trials. However, AEs and clinical endpoints are captured and processed separately with limited information on various aspects of this data collection, its integration, and its variation across sites. OBJECTIVES: To describe all site-reported clinical events in the APPRAISE-2 (Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome) trial and report their seriousness. To evaluate the variability in reporting clinical events across sites and identify characteristics associated with clinical event reporting. METHODS: All clinical events were collected in case report forms (CRF) by site-investigators, as AEs or suspected endpoints. Data on suspected endpoints were collected in specific CRFs (myocardial infarction or unstable angina, cerebrovascular event and bleeding) and sent to review by a clinical events committee (CEC) that adjudicated these events according to predefined criteria. Seriousness criteria was collected for all AEs and suspected endpoints. To explore site-level variability i n event reporting, sites with >=10 participants were i ncluded. Statistical models explored the influence of geographic region and patient characteristics in between-site variability in event reporting. All collected data is centered in the Duke Clinical Research Institute, North Carolina, Unites States. RESULTS: A total of 13.909 clinical events were reported by 858 sites in 39 countries. Most clinical events were AEs (91.6%), followed by suspected endpoints. Of suspected endpoints reviewed by CEC, 66.0% were confirmed. Most CEC-confirmed endpoints met serious criteria (94.0%) and, of CEC-negatively adjudicated endpoints, 63.4% were serious. Of all AEs, 17.9% were considered serious events. Hospitalization was the most common criterion for classification as serious event (N=2594), followed by death (N=321). In models accounting for geographic region, site variation in reporting endpoints and serious AEs was explained by 28.7% and 26.4%, respectively; adding patient characteristics further explained site variation by 25.4% for endpoint reporting and 13.4% for serious AE reporting. Non-serious AE reporting variation was not explained by patient characteristics or region. Several clinical characteristics were associated with clinical event reporting. CONCLUSION: In a multicenter phase III clinical trial, the majority of reported events were non-serious AEs. Geographic region and patient characteristics influenced between-site variability in reporting of clinical endpoints and serious AEs, with limited impact in non-serious AEs. An integrated collection of endpoints and AEs is feasible, possible in a multinational trial and illustrates the shared characteristics of events

Research has shown that the caregiving environment and the type of parent-child interactions that occur during development can have significant impact on future child outcomes for positive as well as negative outcomes (Ruffman, Slade, Devitt, & Crowe, 2006; Fonagy, Gergely, & Target, 2007). Language and emotional expressiveness are common themes that past research suggest are aspects of healthy and open parent-child interactions, and which may have associations with positive child outcomes (Carlson, Mandell, & Williams, 2004). Participants included 1359 children from the longitudinal NICHD Study of Early Child Care—variables were measured at 54 months, 3 rd , 4 th , and 6 th grades and at age 15. The early caregiving environment was found to predict 4 th grade language skills, but this relationship was not mediated by family emotional expressiveness in 3 rd grade. Family emotional expressiveness was found to predict 6 th grade social skills, but this was not mediated by 4 th grade language skills. Evidence of an indirect effect of language skills on social skills was found. Fifth grade language skills were not found to predict adolescent problem behavior, however, an overall significant indirect effect was found. Finally, family emotional expressiveness was found to predict adolescent problem behavior, and this relationship was partially mediated by 6th grade social skills. Direct, indirect, and total effects of the various predictors of adolescent problem behavior are discussed in the final chapter.