A novel finding of a low-molecular-weight compound, SMTP-7, having thrombolytic and anti-inflammatory effects in cerebral infarction of mice

Tissue plasminogen activator (t-PA) has a short therapeutic time window for administration (3 h) and carries a risk of promoting intracerebral hemorrhage. The aim of the present study was to investigate a therapeutic time window and frequency of hemorrhagic region by treatment with Stachybotrys microspora triprenyl phenol-7 (SMTP-7). Thrombotic occlusion was induced by transfer of acetic acid-induced thrombus at the right common carotid artery into the brain of mice. Infarction area, neurological score, edema percentage, and regional cerebral blood flow (CBF) were determined as the index of the efficacy of SMTP-7. In order to evaluate the mechanism of SMTP-7, plasmin activities and the expressions of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and IL-6 mRNA were examined. SMTP-7 (0.1, 1, 10 mg/kg) dose dependently reduced infarction area, neurological score, and edema percentage. Additionally, its therapeutic time window was longer than that of t-PA, a high-molecular-weight compound. In addition, little hemorrhagic region was induced by treatment with SMTP-7. SMTP-7 showed plasmin activity in vivo and caused a decreased CBF to recover. Furthermore, the expressions of inflammatory cytokine mRNA (IL-1β, TNF-α, IL-6) were increased by t-PA treatment 3 h after ischemia but were not induced by SMTP-7 treatment. These results indicate that SMTP-7 shows potential thrombolytic and anti-inflammatory effects as well as a wide therapeutic time window and little hemorrhagic region compared with that of t-PA. Therefore, this novel low-molecular-weight compound may represent a novel approach for the treatment of cerebral infarction

Propensity Score Matching in Randomized Clinical Trials

Cluster randomization trials with relatively few clusters have been widely used in recent years for evaluation of health-care strategies. On average, randomized treatment assignment achieves balance in both known and unknown confounding factors between treatment groups, however, in practice investigators can only introduce a small amount of stratification and cannot balance on all the important variables simultaneously. The limitation arises especially when there are many confounding variables in small studies. Such is the case in the  INSTINCT  trial designed to investigate the effectiveness of an education program in enhancing the tPA use in stroke patients. In this article, we introduce a new randomization design, the balance match weighted (BMW) design, which applies the optimal matching with constraints technique to a prospective randomized design and aims to minimize the mean squared error (MSE) of the treatment effect estimator. A simulation study shows that, under various confounding scenarios, the BMW design can yield substantial reductions in the MSE for the treatment effect estimator compared to a completely randomized or matched-pair design. The BMW design is also compared with a model-based approach adjusting for the estimated propensity score and Robins-Mark-Newey E-estimation procedure in terms of efficiency and robustness of the treatment effect estimator. These investigations suggest that the BMW design is more robust and usually, although not always, more efficient than either of the approaches. The design is also seen to be robust against heterogeneous error. We illustrate these methods in proposing a design for the  INSTINCT  trial.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78638/1/j.1541-0420.2009.01364.x.pd

Training emergency services’ dispatchers to recognise stroke: an interrupted time-series analysis

Background: Stroke is a time-dependent medical emergency in which early presentation to specialist care reduces death and dependency. Up to 70% of all stroke patients obtain first medical contact from the Emergency Medical Services (EMS). Identifying ‘true stroke’ from an EMS call is challenging, with over 50% of strokes being misclassified. The aim of this study was to evaluate the impact of the training package on the recognition of stroke by Emergency Medical Dispatchers (EMDs). Methods: This study took place in an ambulance service and a hospital in England using an interrupted time-series design. Suspected stroke patients were identified in one week blocks, every three weeks over an 18 month period, during which time the training was implemented. Patients were included if they had a diagnosis of stroke (EMS or hospital). The effect of the intervention on the accuracy of dispatch diagnosis was investigated using binomial (grouped) logistic regression. Results: In the Pre-implementation period EMDs correctly identified 63% of stroke patients; this increased to 80% Post-implementation. This change was significant (p=0.003), reflecting an improvement in identifying stroke patients relative to the Pre-implementation period both the During-implementation (OR=4.10 [95% CI 1.58 to 10.66]) and Post-implementation (OR=2.30 [95% CI 1.07 to 4.92]) periods. For patients with a final diagnosis of stroke who had been dispatched as stroke there was a marginally non-significant 2.8 minutes (95% CI −0.2 to 5.9 minutes, p=0.068)reduction between Pre- and Post-implementation periods from call to arrival of the ambulance at scene. Conclusions: This is the first study to develop, implement and evaluate the impact of a training package for EMDs with the aim of improving the recognition of stroke. Training led to a significant increase in the proportion of stroke patients dispatched as such by EMDs; a small reduction in time from call to arrival at scene by the ambulance also appeared likely. The training package has been endorsed by the UK Stroke Forum Education and Training, and is free to access on-line

Impact of regional pre‐hospital emergency medical services in treatment of patients with acute ischemic stroke

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93719/1/j.1749-6632.2012.06746.x.pd

Preventive medical care in remote Aboriginal communities in the Northern Territory: a follow-up study of the impact of clinical guidelines, computerised recall and reminder systems, and audit and feedback

Background Interventions to improve delivery of preventive medical services have been shown to be effective in North America and the UK. However, there are few studies of the extent to which the impact of such interventions has been sustained, or of the impact of such interventions in disadvantaged populations or remote settings. This paper describes the trends in delivery of preventive medical services following a multifaceted intervention in remote community health centres in the Northern Territory of Australia. Methods The intervention comprised the development and dissemination of best practice guidelines supported by an electronic client register, recall and reminder systems and associated staff training, and audit and feedback. Clinical records in seven community health centres were audited at regular intervals against best practice guidelines over a period of three years, with feedback of audit findings to health centre staff and management. Results Levels of service delivery varied between services and between communities. There was an initial improvement in service levels for most services following the intervention, but improvements were in general not fully sustained over the three year period. Conclusions Improvements in service delivery are consistent with the international experience, although baseline and follow-up levels are in many cases higher than reported for comparable studies in North America and the UK. Sustainability of improvements may be achieved by institutionalisation of relevant work practices and enhanced health centre capacity

Knowledge and perception about stroke among an Australian urban population

BACKGROUND: The aim of the study was to measure knowledge about the symptoms, prevalence and natural history of stroke; the level of concern about having a stroke; understanding of the possibilities for preventing stroke, and the relationship between age, sex, country of origin, educational level, income, self-reported risk factors, and the above factors. METHODS: A random sample of households was selected from an electronic telephone directory in Newcastle and Lake Macquarie area of New South Wales, Australia, between 10 September and 13 October 1999. Within each household the person who was between 18 and 80 years of age and who had the next birthday was eligible to participate in the study (1325 households were eligible). The response rate was 62%. RESULTS: The most common symptoms of stroke listed by respondents were "Sudden difficulty of speaking, understanding or reading" identified by 60.1% of the respondents, and "paralysis on one side of body" identified by 42.0% of the respondents. The level of knowledge of the prevalence of a stroke, full recovery after the stroke, and death from stroke was low and generally overestimated. 69.9% of the respondents considered strokes as being either moderately or totally preventable. There were few predictors of knowledge. CONCLUSION: The study suggests that educational strategies may be required to improve knowledge about a wide range of issues concerning stroke in the community, as a prelude to developing preventive programmes

Does Preexisting Antiplatelet Treatment Influence Postthrombolysis Intracranial Hemorrhage in Community‐treated Ischemic Stroke Patients? An Observational Study

Objectives Intracranial hemorrhage ( ICH ) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous ( IV ) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. Methods Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster‐randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow‐up imaging (primary outcome). Symptomatic ICH ( sICH ) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta‐analytic techniques. Results There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (± standard deviation [SD]) age was 69 (±15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = −1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = −1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta‐analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95% CI = 2.3% to 5.6%). The meta‐analytic adjusted OR of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4). Conclusions The authors did not find that preexisting antiplatelet use was associated with postthrombolysis ICH or sICH in this cohort of community treated patients. Preexisting tobacco use, younger age, and lower severity were associated with lower odds of sICH . The meta‐analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH , along with increased odds of sICH in patients with preexisting antiplatelet use. Resumen ¿Influye el Tratamiento Antiagregante Previo en la Hemorragia Intracraneal tras la Trombolisis en los Pacientes con Ictus Isquémicos Tratados en la Comunidad? Un Estudio Observacional Objetivos La hemorragia intracraneal ( HIC ) tras la trombolisis de un ictus agudo se asocia con malos resultados. Los estudios previos de la relación entre el uso de antiagregantes y la seguridad de la trombolisis intravenosa ( IV ) han estado limitados por los porcentajes bajos de sucesos. El objetivo de este estudio fue determinar si el tratamiento antiagregante previo está asociado con la evidencia radiológica de HIC tras el control por los factores de confusión relevantes. Metodología Se identificaron los casos consecutivos de pacientes tratados con trombolisis en el SU de múltiples formas. Se recogieron los datos de forma retrospectiva de cuatro hospitales de 1996 a 2004 y de 24 hospitales distintos de 2007 a 2010 como parte de un ensayo clínico aleatorizado en racimos. Se utilizó la misma tabla resumen de historia clínica durante ambos periodos de tiempo y los datos fueron sometidos a numerosos controles de calidad. Las hemorragias se clasificaron siguiendo una metodología preestablecida: la HIC se definió como la presencia de hemorragia en las interpretaciones radiológicas de las imágenes de seguimiento (resultado primario); y la HIC sintomática ( HIC s) se definió como la HIC radiológica asociada con un empeoramiento clínico. Se construyó un modelo multivariable de regresión logística para ajustar los factores clínicos previamente identificados como relacionados con un la HIC tras la trombolisis. Los análisis de sensibilidad se realizaron mediante técnicas de metanálisis y se combinaron los resultados ajustados y no ajustados de esta investigación con los estudios externos previamente publicados en este tema. Resultados Se incluyeron 830 pacientes, de los cuales el 47% tenía documentado tratamiento antiagregante previo. La media de edad fue de 69 años, y el 53% eran varones. La proporción no ajustada de pacientes con cualquier tipo de HIC fue del 15,1% sin toma de antiagregante y del 19,3% con la toma de antiagregante (diferencia del riesgo absoluto 4,2%, IC 95% = −1,2% a 9,6%); y para las HIC s fue del 6,1% sin toma de antiagregantes y del 9% con la toma de antiagregantes (diferencia absoluta del riesgo 3,1%, IC 95% = −1% a 6,7%). Tras ajustar por los factores de confusión, la toma de antiagregantes no se asoció de forma significativa con la HIC radiológica ( OR 1,1, IC 95% = 0,8 a 1,7]) o HIC s ( OR 1,3, IC 95% = 0,7 a 2,2). En los pacientes de 81 años o más, hubo mayor riesgo de HIC radiológica (diferencia de riesgo absoluta 11,9%, IC 95% = 0,1% a 23,6%). El metanálisis que combinó los hallazgos de esta investigación con los trabajos similares previos encontró un riesgo no ajustado incrementado para la HIC radiológica (diferencia absoluta del riesgo 4,9%, IC 95% = 0,7% a 9%) y de HIC s (diferencia absoluta del riesgo 4%, IC 95% = 2,3% a 5,6%). La odds ratio ajustada del metanálisis de HIC s para los pacientes con tratamiento de antigregantes fue de 1,6 ( IC 95% = 1,1 a 2,4). Conclusiones Los autores no encontraron que la toma previa de antigregantes se asocie con la HIC o la HIC s tras la trombolisis en esta cohorte de pacientes tratados en la comunidad. El consumo previo de tabaco, la edad más joven y la menor gravedad se asociaron con odds ratio menores de HIC s. El metanálisis demostró un incremento bajo, aunque estadísticamente significativo, de riesgo absoluto de HIC radiológica o de HIC s, con una odds ratio aumentada de HIC s en los pacientes con toma previa de antiagregantes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96759/1/acem12077.pd

Addressing the Future Burden of Cancer and Its Impact on the Oncology Workforce: Where Is Cancer Prevention and Control?

The need for cancer professionals has never been more urgent than it is today. Reports project serious shortages by 2020 of oncology health care providers. Although many plans have been proposed, no role for prevention has been described. In response, a 2-day symposium was held in 2009 at The University of Texas MD Anderson Cancer Center to capture the current status of the cancer prevention workforce and begin to identify gaps in the workforce. Five working groups were organized around the following topic areas: (a) health policy and advocacy; (b) translation to the community; (c) integrating cancer prevention into clinical practice; (d) health services infrastructure and economics; and (e) discovery, research, and technology. Along with specific recommendations on these topics, the working groups identified two additional major themes: the difficulty of defining areas within the field (including barriers to communication) and lack of sufficient funding. These interdependent issues synergistically impede progress in preventing cancer; they are explored in detail in this synthesis, and recommendations for actions to address them are presented. Progress in cancer prevention should be a major national and international goal. To achieve this goal, ensuring the health of the workforce in cancer prevention and control is imperative