Economic analysis of the 'Take Charge' intervention for people following stroke: Results from a randomised trial.

OBJECTIVE: To undertake an economic analysis of the Take Charge intervention as part of the Taking Charge after Stroke (TaCAS) study. DESIGN: An open, parallel-group, randomised trial comparing active and control interventions with blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: The Take Charge intervention, a strengths based, self-directed rehabilitation intervention, in two doses (one or two sessions), and a control intervention (no Take Charge sessions). MEASURES: The cost per quality-adjusted life year (QALY) saved for the period between randomisation (always post hospital discharge) and 12 months following acute stroke. QALYs were calculated from the EuroQol-5D-5L. Costs of stroke-related and non-health care were obtained by questionnaire, hospital records and the New Zealand Ministry of Health. RESULTS: One-year post hospital discharge cost of care was mean (95% CI) $US4706 (3758-6014) for the Take Charge intervention group and $6118 (4350-8005) for control, mean (95% CI) difference $ -1412 (-3553 to +729). Health utility scores were mean (95% CI) 0.75 (0.73-0.77) for Take Charge and 0.71 (0.67-0.75) for control, mean (95% CI) difference 0.04 (0.0-0.08). Cost per QALY gained for the Take Charge intervention was $US -35,296 (=£ -25,524, € -30,019). Sensitivity analyses confirm Take Charge is cost-effective, even at a very low willingness-to-pay threshold. With a threshold of $US5000 per QALY, the probability that Take Charge is cost-effective is 99%. CONCLUSION: Take Charge is cost-effective and probably cost saving.

The effect of the Take Charge intervention on mood, motivation, activation and risk factor management: Analysis of secondary data from the Taking Charge after Stroke (TaCAS) trial.

OBJECTIVE: To use secondary data from the Taking Charge after Stroke study to explore mechanisms for the positive effect of the Take Charge intervention on physical health, advanced activities of daily living and independence for people after acute stroke. DESIGN: An open, parallel-group, randomised trial with two active and one control intervention and blinded outcome assessment. SETTING: Community. PARTICIPANTS: Adults (n = 400) discharged to community, non-institutional living following acute stroke. INTERVENTIONS: One, two, or zero sessions of the Take Charge intervention, a self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. MEASURES: Twelve months after stroke: Mood (Patient Health Questionnaire-2, Mental Component Summary of the Short Form 36); 'ability to Take Charge' using a novel measure, the Autonomy-Mastery-Purpose-Connectedness (AMP-C) score; activation (Patient Activation Measure); body mass index (BMI), blood pressure (BP) and medication adherence (Medication Adherence Questionnaire). RESULTS: Follow-up was near-complete (388/390 (99.5%)) of survivors at 12 months. Mean age (SD) was 72.0 (12.5) years. There were no significant differences in mood, activation, 'ability to Take Charge', medication adherence, BMI or BP by randomised group at 12 months. There was a significant positive association between baseline AMP-C scores and 12-month outcome for control participants (1.73 (95%CI 0.90 to 2.56)) but not for the Take Charge groups combined (0.34 (95%CI -0.17 to 0.85)). CONCLUSION: The mechanism by which Take Charge is effective remains uncertain. However, our findings support a hypothesis that baseline variability in motivation, mastery and connectedness may be modified by the Take Charge intervention.

Taking Charge after Stroke: A randomized controlled trial of a person-centered, self-directed rehabilitation intervention.

BACKGROUND AND PURPOSE: "Take Charge" is a novel, community-based self-directed rehabilitation intervention which helps a person with stroke take charge of their own recovery. In a previous randomized controlled trial, a single Take Charge session improved independence and health-related quality of life 12 months following stroke in Maori and Pacific New Zealanders. We tested the same intervention in three doses (zero, one, or two sessions) in a larger study and in a broader non-Maori and non-Pacific population with stroke. We aimed to confirm whether the Take Charge intervention improved quality of life at 12 months after stroke in a different population and whether two sessions were more effective than one. METHODS: We randomized 400 people within 16 weeks of acute stroke who had been discharged to institution-free community living at seven centers in New Zealand to a single Take Charge session (TC1, n = 132), two Take Charge sessions six weeks apart (TC2, n = 138), or a control intervention (n = 130). Take Charge is a "talking therapy" that encourages a sense of purpose, autonomy, mastery, and connectedness with others. The primary outcome was the Physical Component Summary score of the Short Form 36 at 12 months following stroke comparing any Take Charge intervention to control. RESULTS: Of the 400 people randomized (mean age 72.2 years, 58.5% male), 10 died and two withdrew from the study. The remaining 388 (97%) people were followed up at 12 months after stroke. Twelve months following stroke, participants in either of the TC groups (i.e. TC1 + TC2) scored 2.9 (95% confidence intervals (CI) 0.95 to 4.9, p = 0.004) points higher (better) than control on the Short Form 36 Physical Component Summary. This difference remained significant when adjusted for pre-specified baseline variables. There was a dose effect with Short Form 36 Physical Component Summary scores increasing by 1.9 points (95% CI 0.8 to 3.1, p < 0.001) for each extra Take Charge session received. Exposure to the Take Charge intervention was associated with reduced odds of being dependent (modified Rankin Scale 3 to 5) at 12 months (TC1 + TC2 12% versus control 19.5%, odds ratio 0.55, 95% CI 0.31 to 0.99, p = 0.045). CONCLUSIONS: Confirming the previous randomized controlled trial outcome, Take Charge-a low-cost, person-centered, self-directed rehabilitation intervention after stroke-improved health-related quality of life and independence. CLINICAL TRIAL REGISTRATION-URL: http://www.anzctr.org.au. Unique identifier: ACTRN12615001163594.

Secretory carcinoma of the major salivary gland: Provincial population-based analysis of clinical behavior and outcomes.

BACKGROUND: Our aim was to identify the number of cases of secretory carcinoma (SC) of the major salivary gland in a population-based cohort and review its clinical behavior with long-term follow-up. METHODS: All malignant salivary gland tumors (MSGTs) diagnosed between 1980 and 2014 were assessed for histological features compatible with SC and 140 were selected for further analysis. RESULTS: Twenty two new cases of SC were identified, 19 of which were originally classified as acinic cell carcinoma, and 3 as adenocarcinoma, not otherwise specified (NOS). Lymph node involvement was less common in SC tumors (5%) than in the control group (11%). Disease recurrence was seen less frequently in SC (9%) than the control group (20%). Mean disease-free survival was 192 months for SC compared with 162 months for controls (P = 0.15). CONCLUSION: The clinical course of SC is typically indolent with a low risk of relapse not significantly different from other low-grade MSGT.

Manejo de factores de riesgo cardiovascular en Venezuela mediante educación de los médicos que trabajan en atención primaria de salud / Management of cardiovascular risk factors in Venezuela by educating physicians working in primary healthcare services

Estudios recientes en América Latina corroboraron la prevalencia de la hipertensión arterial, el colesterol elevado en plasma, los trastornos metabólicos y otros factores de riesgo cardiovascular (FRCV), todo esto sumado a la falta de control de la enfermedad, la escasa adhesión al tratamiento y el uso de pocas medidas preventivas, lo que derivó en la necesidad de educar tanto al médico como al paciente. Se han realizado estudios limitados para demostrar la eficacia del desarrollo profesional continuo y su capacidad de influir positivamente en los indicadores de salud del paciente. En Venezuela se llevó a cabo un estudio para tratar de medir la efectividad de un curso combinado basado en actividades online y presenciales sobre el manejo de los FRCV, dirigido a médicos que trabajan en atención primaria. Un grupo piloto de 37 médicos de atención primaria del área metropolitana de Caracas completó una intervención educativa de 12 semanas, la cual consistió en sesiones semanales en línea, utilizando la estrategia educativa basada en problemas sobre el manejo de los FRCV, así como talleres presenciales relacionados con los cambios de comportamiento del médico y del paciente, utilizando los principios de la educación terapéutica. Se trabajó con una cohorte de 303 pacientes con hipertensión arterial de grado I-II no controlada y/o colesterol plasmático elevado, y se llevó a cabo un seguimiento durante seis meses. Los resultados evidenciaron cambios significativos en los médicos respecto a los aspectos cognitivos y al estilo de su práctica profesional en el manejo de los FRCV. Los participantes se mostraron muy satisfechos con el contenido y el formato de la intervención educativa. De igual manera, encontramos un resultado positivo en la inducción de cambios en toda la cohorte de pacientes, sobre todo en el perfil lipídico, la presión arterial y la modificación del estilo de vida. Sería interesante su aplicación a mayor escala para medir su efectividad a largo plazo

Recent studies in Latin-America corroborated the prevalence of hypertension, elevated plasma cholesterol, metabolic disorders and other cardiovascular risk factors (CVRF) along with lack of disease awareness. Treatment and preventive measures indicated the urgent need for patient and physician education. Limited studies have been conducted to demonstrate the effectiveness of continual professional development (CPD) and its ability to positively improve health care outcomes. A study was done in Venezuela to measure the effectiveness of a blended web-based education in the management of CVRF by primary health care physicians (PCP), working in primary care services. A pilot group of 37 PCP, from the Caracas metropolitan area, completed a 12-week educational intervention consisting of weekly online problem based sessions on CVRF management and face-to-face workshops on physician and patient behavioural changes, using principles of therapeutic education. A cohort of 303 of their patients with uncontrolled grade I-II arterial hypertension and/or elevated plasma cholesterol were included and followed up for a 6-month period. Significant changes in the cognitive aspects and attitudes about the management of CVRF occurred among the PCP, who were highly satisfied with the content and format of the educational intervention. We also found a positive role in inducing changes in the entire patient cohort, particularly on the plasma lipid profile, blood pressure, and lifestyle changes. Results of this pilot study reflect the effective use of CPD on patient care and PCP interactions in creating synergy and understanding with participating institutions. There is a need of large scale implementation and more extensive comparison with other educational approaches

Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor.

The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3-5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited.

Experiencia estratégica internacional para el desarrollo profesional continuo y su impacto en la atención primaria de salud / An international strategic experience for continuing professional development and its impact on primary health care

A los dinámicos y profundos cambios científicos, tecnológicos, demográficos y epidemiológicos en el área de la salud, se unen demandas de la población para mejores y más eficientes servicios. Se da el hecho de que la educación médica de pregrado y posgrado no garantiza las competencias de forma indefinida, lo que hace necesarios mecanismos que aseguren una mejor calidad asistencial. El Consorcio Proyecto Global (PGC) sugiere una estrategia integral de educación médica continua y de desarrollo profesional continuo estructurada, simplificada, evaluada y acreditada para contribuir a enfrentar estos desafíos. Se ejecutó el proyecto en dos países como prueba piloto (Rusia y Venezuela). Se implementó en cinco fases: construcción de relaciones institucionales, determinación de necesidades educativas, implementación y medición del impacto, difusión del mensaje y expansión de experiencias, y ajuste e institucionalización del proyecto. Se involucró a un número significativo de médicos que trabajan en los servicios de atención primaria de salud. Se identificaron y probaron estándares globales de educación médica continua y desarrollo profesional continuo, y se diseñó un currículo nuclear, comenzando con el área cardiovascular, con el objeto de mejorar los niveles de conocimiento y la práctica de los médicos participantes, y evidenciarlo en cambios positivos en indicadores de los pacientes usuarios. Finalmente, se llegó a la etapa de institucionalización y reforzamiento continuo, en la cual el PGC funcionó como un proyecto piloto de intercambio internacional y como posible proveedor de educación médica continua y desarrollo profesional continuo, con alta calidad, costos razonables y acreditación académica

Project Globe Consortium (PGC) integrated one simplified strategy in continuing medical education and continuing professional development. It was designed as an answer to the fast and intense changes in science, technology, demography, epidemiology, the increasing demands of the population, and the changing role of physicians in the current health care systems, under the awareness that the undergraduate medical education does not guarantee the required competencies indefinitely thus implying the need of necessary mechanisms to ensure quality and professional healthcare. The project was implemented in two pilot countries (Russia and Venezuela). It was developed in five phases: building up on institutional relationships, identifying local champions; identifying educational needs; implementation and impact measurement; sharing the message and experiences; maturing adjustments and institutionalization of the project. A significant number of physicians working in primary health care settings were involved. Global standards of continuing medical education and continuing professional development were identified and tested. A core curriculum was designed, starting with cardiovascular risk factors, to improve knowledge levels and professional practice of the physicians involved, along with significant changes in patient indicators as biomarkers. Finally, the project reached the stage of institutionalization and continuous reinforcement in which the PGC represented an international networking and potential continuing medical education and continuing professional development, provider of, high quality, at reasonable costs and with academic accreditation

Efectos de una intervención educativa en el manejo clínico de los factores de riesgo cardiovascular en atención primaria de salud. Experiencia con Project Globe Consortium en Rusia / Effects of an educational intervention in the clinical management of cardiovascular risk factors in primary healthcare. Experiment with the Project Globe Consortium in Russia

Introducción. Las enfermedades cardiovasculares son la principal causa de morbimortalidad y de carga de enfermedad global. Por ello, el manejo apropiado de sus factores de riesgo (FRCV) en la prevención primaria y secundaria del daño cardiovascular es de primordial importancia. Se ha cuestionado el papel de la educación médica continuada en mejorar el desempeño profesional. Diseñamos una intervención educativa destinada tanto a médicos de atención primaria bajo el contexto de desarrollo profesional continuo como a sus pacientes, utilizando principios de educación terapéutica en un diseño abierto no controlado. El objetivo fue evaluar su impacto en parámetros cognitivos y actitudinales, y su efecto en marcadores de riesgo. Sujetos y métodos. 30 médicos de policlínicas ambulatorias en el área metropolitana de Moscú fueron invitados a participar en un programa de actualización sobre el manejo de FRCV (72 h). Posteriormente, 600 pacientes con FRCV participaron en 12 sesiones educativas durante un periodo de tres meses. Los pacientes fueron evaluados clínicamente de forma trimestral durante 12 meses. Resultados. Se observó una reducción significativa de los FRCV (hipertensión arterial, hipercolesterolemia, peso corporal, hiperlipidemia, tabaquismo) durante el periodo de evaluación, acompañados de cambios en el estilo de vida probablemente como reflejo de una mejor adherencia al tratamiento. La evaluación cognitiva y las actitudes hacia el control de FRCV tuvieron mejores calificaciones tanto en los médicos como en sus pacientes. Conclusiones. La educación secuencial de médicos y de sus pacientes en el manejo de FRCV parece tener un impacto favorable en la evolución clínica de sus marcadores, pero se precisan estudios controlados para confirmar estos hallazgos preliminares (AU)

Introduction. Cardiovascular diseases are the main cause of morbimortality and of burden of disease in both developed and developing countries. Therefore the appropriate management of cardiovascular risk factors (CVR) in primary and secondary prevention is highly relevant. The role of continuing medical education and continuing professional development on performance improvement has been questioned. An educational intervention addressed to primary care physicians as continuing professional development as well as to their patients with CVR was devised. Principles of therapeutic education were used. The objective was to evaluate the impact of both educational interventions on cognitive and attitudinal parameters of CVR, as well as the impact on their surrogate markers of disease progression. Subjects and methods. 30 primary care physicians from outpatient clinics in the Moscow metropolitan area were invited to the educational intervention (lectures, seminars, workshops for a total of 72 h during one month). Afterwards 600 patients with CVR attending the same clinics received education on CVR (12 sessions over 3 months). Patients were clinically evaluated on quarterly bases during one year of follow up. Results. A significant reduction in surrogate markers of CVR was observed (blood pressure, serum lipids, weight, smoking, etc.) among the patient cohort as a probable consequence of leveraged therapeutic adherence. Likewise, the knowledge and attitudes improved significantly both in physicians and their patients. Conclusions. A sequential education of physicians and their patients with CVR seems to have a favorable impact upon surrogate markers of risk. Further controlled studies are needed to confirm these preliminary results (AU)

Improved stroke care processes and outcomes following the institution of an acute stroke unit at a New Zealand district general hospital.

AIMS: To examine whether stroke care processes and outcomes are improved following the institution of an acute stroke unit (ASU) at a medium-sized New Zealand hospital. METHODS: Two retrospective audits over 12-month periods were carried out at Hutt Valley Hospital before and after the institution of a 6-bed ASU. Data was collected on demographics, length of stay, stroke type, investigations, processes of care and outcomes. RESULTS: 139 strokes pre ASU and 155 strokes post ASU were studied. 86.8% of strokes received stroke unit care in the 2009 audit. There were more intracerebral haemorrhages in 2006 (17.2% vs. 9.0%). Significant improvements were seen between 2006 and 2009 in time to aspirin administration (52.7 versus 14.5 hours), swallow assessment within 24 hours (88.5% versus 96.1%), lag time to carotid Doppler studies (21 days versus 4.5 days), pressure risk assessments (19.6%, versus 87.2%) and urinary infection rates (10.8% versus 2.0% ). Total length of stay (TLOS) and mortality were reduced but the difference was not statistically significant. (20.5 days versus 18.3 days p=0.34, Inpatient mortality 16.2% versus 10% p=0.12). CONCLUSIONS: The introduction of an ASU has resulted in improvements in several key processes of stroke care. Overall mortality and total length of stay showed a trend to improvement after the establishment of an ASU.

Carotid endarterectomy: a Southern North Island regional consensus statement.

AIMS: The aim of this project was to employ interdepartmental and cross district health board collaboration to reach a regional consensus on the management of patients who may benefit from carotid endarterectomy. METHODS: All regional stroke physicians, neurologists, and vascular surgeons met to review relevant literature and local audits and to discuss best management strategies suited to the region. RESULTS: A consensus statement was agreed upon and is presented here along with a summary of the supporting scientific evidence. DISCUSSION: Regional interdisciplinary collaboration proved an effective way to reach a carotid endarterectomy management consensus across a wider geographical area that is served by a single vascular surgery department. This approach could serve as a model for other regional initiatives.

HER2 testing in a population-based study of patients with metastatic breast cancer treated with trastuzumab.

CONTEXT: The development of trastuzumab has led to new therapeutic strategies for patients with breast cancer. Trastuzumab has been shown to only be effective in those patients whose cancers are HER2 positive by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). OBJECTIVE: To determine the accuracy of HER2 testing in 2 provinces in Canada. DESIGN: Patients with metastatic breast cancer diagnosed between 1999 and 2002 who were HER2 positive in the local laboratories were included in this study. All cases were retested centrally, by IHC (using 4 methods) and FISH. In addition, 205 locally reported HER2-negative metastatic breast cancer cases were retested centrally. RESULTS: Concordance between the 505 local IHC-positive cases with central IHC testing varied between 79.3% and 89.6% depending on the IHC method and scoring method used. HER2 gene amplification by FISH was present in 86.1% of local IHC-positive cases. Concordance between the 205 local IHC-negative tumors with central testing ranged between 94.8% and 100% for IHC and was 98.5% for FISH. CONCLUSIONS: This study demonstrated that locally reported HER2-negative results were highly accurate, but less accuracy was demonstrated with local HER2-positive results. These results emphasize the need for participation in a quality assurance program.

Molecular predictive factors in patients receiving trastuzumab-based chemotherapy for metastatic disease.

BACKGROUND: Trastuzumab-based chemotherapy can improve median survival in the metastatic setting when used in patients with cancer that overexpresses HER2/neu. In addition to HER2 expression, other molecular markers are needed to better predict outcomes after the initiation of trastuzumab-based chemotherapy and to elucidate potential mechanisms of resistance to trastuzumab. PATIENTS AND METHODS: Patients with clinical documentation of HER2/neu-overexpressing metastatic breast cancer treated with trastuzumab between 1998 and 2004 were identified from the British Columbia Provincial Pharmacy Database. Tissues were obtained for microarray analysis of 153 of 306 patients who fit our clinical criteria. Tissue microarrays were constructed for the analysis of multiple molecular factors, and results were correlated to clinical outcomes. Immunohistochemistry was performed on the microarray specimens, and results were correlated with survival and time to progression. RESULTS: Factors commonly associated with poor prognosis in the metastatic setting in general, including short disease-free intervals, high tumor grade, and low estrogen receptor status, were all associated with poor survival in this population with HER2 overexpression. Overexpression of HER3 was observed in 9% of specimens and was associated with a trend toward worse overall survival (P = 0.1). HER3 expression was not correlated with a significant difference in time to progression but did trend to predict for worse survival after progression (P = 0.06). In multivariate analysis, tumor grade and HER3 expression were significantly predictive of overall survival. Phosphatase and tensin homologue status did not appear to correlate with response or survival. CONCLUSION: Our findings suggest that prognosis after initiation of trastuzumab-based chemotherapy depends, in part, on coexpression of HER3.

Can cytology accurately predict benign follicular nodules?

BACKGROUND: The reliability of fine-needle aspiration (FNA) biopsy in differentiating benign from malignant follicular lesions of the thyroid has been the subject of renewed debate recently. Although surgical excision has been recommended for most follicular lesions identified by cytology, this approach may not be necessary in all cases. The goal of this study was to determine whether FNA could be used as a diagnostic tool to safely identify patients with follicular thyroid nodules who do not require immediate surgical intervention. METHODS: A retrospective review was performed on a sample of 24 patients diagnosed with either follicular adenoma or follicular carcinoma after surgical excision of a thyroid nodule. The initial FNA biopsies were independently reviewed by two experienced cytopathologists in a blinded fashion and subsequently compared with final histologic diagnoses. RESULTS: For pathologist A, overall accuracy was 58%. The positive predictive value (PPV) of a benign diagnosis was 82%; PPV of a malignant diagnosis was 38%. For pathologist B, overall accuracy was 63%. The PPV of a benign diagnosis was 83%; PPV of a malignant diagnosis was 42%. CONCLUSIONS: This study suggests that in follicular lesions of the thyroid, a benign FNA biopsy report from an experienced cytopathologist has a high positive predictive value. The predictive value may not, however, be high enough to preclude surgery; other factors may need to be considered before recommending a nonoperative approach.

Evidence for inpatient rehabilitation as an effective intervention.

Rehabilitation in inpatient settings is expensive and staff-intensive. It is necessary for such services to demonstrate effectiveness to justify this. In contrast to popular notions, evidence for the effectiveness of inpatient rehabilitation does exist and is reviewed in this article. In particular, there is very good evidence for specialized inpatient stroke care and rehabilitation.

Interphase fluorescence in situ hybridization and DNA flow cytometry analysis of medulloblastomas with a normal karyotype.

Interphase fluorescence in situ hybridization (FISH) with chromosome 3 and 17 centromeric probes and DNA flow cytometry were used for a retrospective study of nine pediatric medulloblastomas with normal karyotypes after tissue culture. The FISH analysis of medulloblastoma touch preparations showed that in seven of nine tumors, a significant proportion of nuclei had an increased number of centromeric signals for the selected chromosomes. In six of seven cases, this increase was caused by the presence of triploid and tetraploid clones as established by flow cytometry of paraffin-embedded tumors. These findings show that molecular cytogenetic analysis combined with DNA flow cytometry is necessary for all pediatric medulloblastomas diagnosed as cytogenetically normal on cultured tumor tissue.