INFLUENCE OF HEALTH TECHNOLOGY ASSESSMENT AND ITS MEASUREMENT.

OBJECTIVES: The aim of this study was to obtain information on methods used to measure health technology assessment (HTA) influence, decisions that were influenced, and outcomes linked to HTA. METHODS: Electronic databases were used to locate studies in which HTA influence had been demonstrated. Inclusion criteria were studies that reliably reported consideration by decision makers of HTA findings; comparative studies of technology use before and after HTA; and details of changes in policy, health outcomes, or research that could be credibly linked to an HTA. RESULTS: Fifty-one studies were selected for review. Settings were national (24), regional (12), both national and regional (3) hospitals (9), and multinational (3). The most common approach to appraisal of influence was review of policy or administrative decisions following HTA recommendations (51 percent). Eighteen studies (35 percent) reported interview or survey findings, thirteen (26 percent) reviewed administrative data, and six considered the influence of primary studies. Of 142 decisions informed by HTA, the most common types were on routine clinical practice (67 percent of studies), coverage (63 percent), and program operation (37 percent). The most frequent indications of HTA influence were on decisions related to resource allocation (59 percent), change in practice pattern (31 percent), and incorporation of HTA details in reference material (18 percent). Few publications assessed the contribution of HTA to changing patient outcomes. CONCLUSIONS: The literature on HTA influence remains limited, with little on longer term effects on practice and outcomes. The reviewed publications indicated how HTA is being used in different settings and approaches to measuring its influence that might be more widely applied, such as surveys and monitoring administrative data.

Risk of pancreatic cancer in breast cancer families from the breast cancer family registry.

BACKGROUND: Increased risk of pancreatic cancer has been reported in breast cancer families carrying BRCA1and BRCA2 mutations; however, pancreatic cancer risk in mutation-negative (BRCAX) families has not been explored to date. The aim of this study was to estimate pancreatic cancer risk in high-risk breast cancer families according to the BRCA mutation status. METHODS: A retrospective cohort analysis was applied to estimate standardized incidence ratios (SIR) for pancreatic cancer. A total of 5,799 families with ≥1 breast cancer case tested for mutations in BRCA1 and/or BRCA2 were eligible. Families were divided into four classes: BRCA1, BRCA2, BRCAX with ≥2 breast cancer diagnosed before age 50 (class 3), and the remaining BRCAX families (class 4). RESULTS: BRCA1 mutation carriers were at increased risk of pancreatic cancer [SIR = 4.11; 95% confidence interval (CI), 2.94-5.76] as were BRCA2 mutation carriers (SIR = 5.79; 95% CI, 4.28-7.84). BRCAX family members were also at increased pancreatic cancer risk, which did not appear to vary by number of members with early-onset breast cancer (SIR = 1.31; 95% CI, 1.06-1.63 for class 3 and SIR = 1.30; 95% CI, 1.13-1.49 for class 4). CONCLUSIONS: Germline mutations in BRCA1 and BRCA2 are associated with an increased risk of pancreatic cancer. Members of BRCAX families are also at increased risk of pancreatic cancer, pointing to the existence of other genetic factors that increase the risk of both pancreatic cancer and breast cancer. IMPACT: This study clarifies the relationship between familial breast cancer and pancreatic cancer. Given its high mortality, pancreatic cancer should be included in risk assessment in familial breast cancer counseling.

Eficacia y seguridad del uso de lenalidomida para el tratamiento del mieloma múltiple / Efficacy and safety of lenalidomide for the treatment of multiple myeloma

INTRODUCCIÓN: El Mieloma Múltiple (MM) es una enfermedad hematológica maligna que afecta las células plasmáticas produciendo su proliferación en la médula ósea produciendo inmunoglobulina monoclonal. Es una enfermedad incurable. La vida del paciente se puede prolongar con altas dosis de quimioterapia y trasplante de células madres autólogas. Representa el 0.8% de todos los cánceres a nivel mundial, con una mayor incidencia según la edad (el 99% de los casos diagnosticados es en personas mayores de 40 años). OBJETIVO: El objetivo del presente reporte es evaluar la eficacia y seguridad de Lenalidomida (REVLIMID®) en el tratamiento del MM, para su posible incorporación al FTM. MÉTODO: Se realizó una búsqueda sistemática de ensayos clínicos aleatorizados y meta-análisis en las bases de datos Medline/Pubmed y la Colaboración Cochrane, así también como en las publicaciones de organizaciones científicas internacionales (NICE, INESSS, EMA, FDA). Las publicaciones encontradas fueron estudiadas y su calidad evaluada. MÉTODO: Se realizó una búsqueda sistemática de ensayos clínicos aleatorizados y meta-análisis en las bases de datos Medline/Pubmed y la Colaboración Cochrane, así también como en las publicaciones de organizaciones científicas internacionales (NICE, INESSS, EMA, FDA). Las publicaciones encontradas fueron estudiadas y su calidad evaluada. RESULTADOS: Se encontraron dos ensayos clínicos aleatorizados principales de alta calidad sobre el tratamiento de Lenalidomida en el mieloma múltiple. Uno de ellos realizado en Norte América mostró que la mitad de los pacientes sobrevivieron aproximadamente 29.6 meses (para el grupo tratado con Lenalidomida + dexametasona) comparado a 20.2 meses (para el grupo tratado con dexametasona + placebo). El segundo ensayo realizado en Europa, Australia e Israel reportó un 51% mayor riesgo de morir en el grupo no tratado comparado con el grupo de Lenalidomida. El avance de la enfermedad se produjo a los 11.3 meses en la mitad de los pacientes tratados con Lenalidomida comparado a 4.7 meses en el grupo no tratado. Los efectos adversos severos en el grupo tratado con Lenalidomida en el ensayo en Norte América fue de 85.3% versus 73.1% en el grupo placebo. El 19.8% de los pacientes tratados con Lenalidomida abandonaron el estudio debido a los eventos adversos comparado a 10.2% en el grupo no tratado. En el otro estudio el 76.1% de los pacientes en Lenalidomida tuvieron que reducir la dosis o abandonar el estudio comparado a 56.9% en el grupo no tratado. DISCUSIÓN: La evidencia obtenida a partir de la búsqueda bibliográfica de la literatura científica de Lenalidomida para el tratamiento de Mieloma Múltiple indica beneficio de Lenalidomida en pacientes que han tenido terapias previas con otros fármacos. Existen agencias de evaluación y organismos regulatorios que recomiendan su uso en pacientes que hayan recibido otros tratamientos anteriores. CONCLUSIONES: Lenalidomida en combinación con dexametasona como segunda línea de tratamiento mostró ser más efectiva que dexametasona en dosis altas en los dos estudios de alta calidad realizados. A pesar de ello, los efectos adversos fueron más frecuentes con Lenalidomida y más pacientes abandonaron el estudio o redujeron la dosis recomendada. Es necesario realizar un análisis costo efectividad de esta droga antes de decidir su ingreso al FTM.(AU)

INTRODUCTION: Multiple Myeloma (MM) is a haematological malignant condition affecting the proliferation of plasma cells in the bone marrow leading to the over-production of monoclonal immunoglobulins. It is an incurable disease. The patient's life can be prolonged with high-dose chemotherapy and autologous stem cells transplantation. It represents 0.8% of all cancers worldwide, displaying an increased incidence with increasing age (99% of diagnosed cases are over 40 years of age). OBJECTIVE: The purpose of this report is to evaluate the efficacy and safety of Lenalidomide (REVLIMID®) for the treatment of MM, for its possible inclusion in the Uruguayan National Formulary. METHODOLOGY: A systematic search for randomized clinical trials (RCT) and meta-analysis published in the scientific literature was performed consulting the following databases: Medline, Pubmed and Cochrane Collaboration. Publications available in international scientific organizations (NICE, INESSS, EMA, FDA) were also searched for. All found publications were studied and its quality assessed. RESULTS: There were two main high-quality RCTs for the treatment of multiple myeloma with REVLIMID. One of them took place in America and showed that half of patients survived approximately 29.6 months (for the lenalidomide + dexamethasone group) compared to 20.2 months (for the dexamethasone + placebo group. The second trial was conducted in Europe, Australia and Israel, and reported a 51% greater risk of dying in the comparison group versus the Lenalidomide group. Disease progression occurred at 11.3 months in half of the patients treated with Lenalidomide compared to 4.7 months in the comparison group. Severe side effects in the Lenalidomide group of the North America ́s RCT was 85.3% versus 73.1% in the placebo group. 19.8% of patients treated with Lenalidomide abandoned the trial due to side effects compared to 10.2% of patients in the comparison group. In the second RCT, 76.1% of patients treated with Lenalidomide had to reduce the dose or drop out of the study compared to 56.9% in the comparison group. DISCUSSION: The evidence drawn from the scientific literature on Lenalidomide for the treatment of multiple myeloma shows that treatment with this drug may benefit patients who have previously received treatment with other drugs. Furthermore, Technology Assesment Agencies and pharmaceutical regulatory bodies recommend its use as a second or third line of treatment. CONCLUSIONS: In the two high-quality RCTs performed and found in the literature, Lenalidomide (as a second-line treatment) when combined with dexamethasone proved to be more effective than high doses of dexamethasone, although side effects were more frequent, and more patients abandoned the study or had to reduce the initial dose of Lenalidomide. It is recommended to look at the cost-effectiveness of this drug before deciding on its inclusion in the Uruguayan National Formulary.(AU)

Eficacia y seguridad del uso de ácido alfa lipoico para el tratamiento de la polineuropatía diabética / Efficacy and safety of the use of alpha lipoic acid for the treatment of diabetic polyneuropathy

INTRODUCCIÓN: La polineuropatía es una de las complicaciones más frecuente de la diabetes mellitus. Las lesiones estructurales más frecuentemente demostradas se caracterizan por la atrofia y lesiones estructurales específicas. Dicha condición médica está relacionada con alta morbilidad, utilización alta del sistema de salud y calidad de vida comprometida por el dolor sufrido por el paciente. La prevalencia de Polineuropatía diabética se presenta en el 5% al 80% de los diabéticos, dependiendo de los criterios diagnósticos utilizados y del tiempo desde el la aparición de la diabetes. OBJETIVOS. Evaluar la eficacia y seguridad del ácido Alfa Lipoico en el tratamiento de la Polineuropatía Diabética para su posible incorporación al FTM. MÉTODOS: La búsqueda de información comenzó con una búsqueda de la literatura científica en la base de Revisiones de la Colaboración Cochrane, en Medline, y posteriormente en las organizaciones internacionales científicas NICE, centro de revisiones y diseminación de la universidad de York (Database HTA) e INESSS. Se evaluó el efecto del Ácido Alfa Lipoico comparado con la alternativa terapéutica (Gabapentina). RESULTADOS: No se encontraron revisiones del Ácido Alfa Lipoico pero si existe una revisión de la Gabapentina para el dolor neuropático en la Cochrane Collaboration. Se encontraron varios ensayos aleatorizados y una revisión sistemática, todos comparando el tratamiento con Acido Alfa Lipoico versus placebo no comparados con la alternativa terapéutica. DISCUSIÓN: Existe en el FTM un fármaco para la neuropatía diabética (Gabapentina). No se encontró ningún estudio aleatorizado del Ácido Alfa Lipoico versus la Gabapentina u otras tecnologías alternativas. Igualmente, al consultar las guías internacionales no figura el Ácido Alfa-Lipoico en ninguna de las guías médicas como recomendación para la neuropatía diabética. CONCLUSIÓN: No es posible acceder a la inclusión de este fármaco en el Formulario Terapéutico de Medicamentos con el presente nivel de información tanto nacional como internacional.(AU)

INTRODUCTION: Polyneuropathy is among the most frequent complications in diabetes mellitus. The most common lesions are characterized by atrophy and specific structural lesions. Such medical condition is related to high morbility, low quality of life and relies heavily on health services mostly due to the associated pain experienced by the patient. Diabetic polyneuropathy is found in 5 to 80% of diabetic patients, depending on the diagnostic criteria and the time since diabetes started. OBJECTIVE: The purpose of the present report is to assess the scientific literature regarding the efficacy and safety of Lipoic Acid for the treatment of Diabetic Polyneuropathy, in order to consider its possible inclusion in the Uruguayan National Formulary. METHODOLOGY: A comprehensive literature review was performed, accessing Cochrane Collaboration Reviews, Medline, NICE, Centre for Reviews and Dissemination of the University of York (HTA database), INESSS, and scientific publications derived from the articles found in the previous database. The assessment was done comparing Lipoic acid to other alternative therapeutic option (Gabapentin). All publications were studied and their quality assessed. RESULTS: There were no reviews found in the literature on Lipoic Acid compared to Gabapentine, although there was a Cochrane review of Neuropathic Pain and Gabapentine. There were a few randomized trials and a systematic review, all comparing treatment with Lipoic acid and placebo, and not to Gabapentine. DISCUSSION: There already exists a pharmaceutical drug for Diabetic Neuropathy (Gabapentina) in the National Formulary. There were no randomized trials on Lipoic acid versus Gabapentina or other therapeutic options. Similarly, when consulting international guidelines there was no information or recommendation of Lipoic acid for Diabetic Neuropathy. Conclusion. There is not enough evidence (national or international) to consider the inclusion of Lipoic acid in the Uruguayan National Formulary. CONCLUSION: There is not enough evidence (national or international) to consider the inclusion of Lipoic acid in the Uruguayan National Formulary.(AU)

Eficacia y seguridad del uso de decitabina: 5-AZA2': deoxicitidina para el tratamiento del síndrome mielodisplásico / Efficacy and safety of the use of decitabine: 5-AZA2': deoxycytidine for the treatment of myelodysplastic syndrome

INTRODUCCIÓN: Síndrome Mielodisplásico (myelodysplastic syndrome, SMD) se denomina a un grupo de afecciones que ocurren cuando se dañan las células productoras de sangre en la médula ósea. Su prevalencia es de 4.4 casos por cada 100.000 personas. OBJETIVO: Determinar la eficacia y la seguridad de DECITABINA: 5-AZA-2´-DEOXICITIDINA, en el tratamiento del Síndrome Mielodisplásico, para su posible incorporación al FTM. METODOLOGÍA: La búsqueda de información científica se realizó accediendo a la base de Revisiones de la Colaboración Cochrane, en Pubmed, NICE, Centro de Revisiones y Diseminación de la Universidad de York (Database HTA) y se obtuvieron publicaciones derivadas de las referencias bibliográficas de las publicaciones encontradas por estos medios. RESULTADOS: Los estudios comparados con el mejor tratamiento de soporte indican que la Decitabina muestra, en algunos parámetros, un avance en el tratamiento del paciente con síndrome Mielodisplásico (mediana de sobrevida libre de progresión 6.6 meses versus 3.0 meses), aunque no modifica la Sobrevida Global. La evidencia publicada sobre eventos adversos indicó que el tratamiento con Decitabina muestra un porcentaje significativamente mayor de efectos secundarios al tratamiento comparado con el mejor tratamiento de soporte (neutropenia febril grado 3-4, 25% versus 7% con el MTS; hipoplasia, 14% versus 0% en el MTS). La comparación de Decitabina con tratamiento con quimioterapia se evaluó en un estudio no aleatorizado mostrando beneficios para la Decitabina en la sobrevida y en la mortalidad a 3 meses. Se encontró poca evidencia comparando la Decitabina a otros agentes hipometilantes, y una comparación indirecta con la 5-azacitidina favoreció a esta última. DISCUSIÓN: La evidencia obtenida del uso de la Decitabina en el SMD no mostró resultados concluyentes para varias de las medidas evaluadas hasta el presente, frente a otras alternativas médicas. Las investigaciones realizadas hasta ahora son escasas y en algunos casos no tienen la calidad necesaria para indicar una diferencia importante en el tratamiento con este fármaco. CONCLUSIÓN: Se considera que la evidencia existente es insuficiente hasta el momento para concluir sobre la eficacia de este fármaco en el tratamiento de los Síndromes Mielodisplásicos especialmente al compararlo con otros fármacos como ser los hipometilantes que también se han evaluado para su ingreso al FTM.(AU)

Low prevalence of depression and anxiety is linked to statutory retirement ages rather than personal work exit: a national survey.

BACKGROUND: Common mental disorder prevalence decreases substantially around the conventional retirement age for men in the UK, but trends for older women are more continuous. Prevalence changes in depression and anxiety around retirement are less clear, as is the role of risk factors. The aim of this study was to establish whether work status, age or other known risk factors account for the reduced prevalence of depressive episode and anxiety disorder around retirement ages for men and for women. METHOD: The British Psychiatric Morbidity Survey (BPMS) 2000 was analysed, including 1875 men and 2253 women aged 45-75 years. Diagnoses were from the Revised Clinical Interview Schedule (CIS-R). Logistic models were adjusted for sociodemographic factors, social network, work status, life events, physical illness and disability. RESULTS: There are marked reductions in the prevalence of depressive episode after 60 years for women [60% lower prevalence, 95% confidence interval (CI) 40-80] and 65 years for men (90% lower prevalence, 95% CI 70-100), compared to the youngest age groups. For anxiety disorder, the reduction in prevalence was 80% (95% CI 60-90) for men and 40% (95% CI 20-60) for women. In fully adjusted multivariate models, the strong association between diagnoses and age groups remained, for both genders. Work status was a significant factor for men but not for women. CONCLUSION: There is a discontinuity in the prevalence of depressive episode for both men and women, coinciding with statutory retirement ages. No studied risk factor reduced the associations between age group and disorders. This population scale recovery may provide a model for understanding non-genetic factors.

Mental health and the timing of men's retirement.

BACKGROUND: Analysis of the Psychiatric Morbidity Survey of Great Britain showed that the prevalence of common mental disorders was lower amongst men at or above Britain's state pension age of 65, relative to younger men. Retirees below this age had consistently higher rates of mental disorders than working men. In contrast, the low prevalence of mental disorders amongst retirees aged 65 and older was similar to that of their working peers. The aim of this analysis was to investigate this pattern of results in a national sample of Australian men, and the mediating role of socio-demographic factors. METHOD: Data were from the Household, Income and Labour Dynamics (HILDA) in Australia survey (2003). The analyses included men aged 45-74 years who were active in the labour force (n = 1309), or retired (n = 635). Mental health was assessed using the mental health scale from the Short-Form 36 Health Questionnaire. RESULTS: Retirees were more likely to have mental health problems than their working peers, however this difference was progressively smaller across age groups. For retirees above, though not below, the age of 55 this difference was explained by poorer physical functioning. When age at retirement was considered it was found that early retirees who were now at or approaching the conventional retirement age did not display the substantially elevated rates of mental health problems seen in their younger counterparts. Further, men who had retired at age 60 or older did not display an initially elevated rate of mental health problems. CONCLUSIONS: The association between retirement and mental health varies across older adulthood. Retired British and Australian men below the conventional retirement age of 65 are more likely to have mental health problems relative to their working peers, and retirees above this age. However, poor mental health appears to be linked to being retired below this age rather than an enduring characteristic of those who retire early.

Retirement and mental health: analysis of the Australian national survey of mental health and well-being.

Nation-wide research on mental health problems amongst men and women during the transition from employment to retirement is limited. This study sought to explore the relationship between retirement and mental health across older adulthood, whilst considering age and known risk factors for mental disorders. Data were from the 1997 National Survey of Mental Health and Well-being, a cross-sectional survey of 10,641 Australian adults. The prevalence of depression and anxiety disorders was analysed in the sub-sample of men (n = 1928) and women (n = 2261) aged 45-74 years. Mental health was assessed using the Composite International Diagnostic Instrument. Additional measures were used to assess respondents' physical health, demographic and personal characteristics. The prevalence of common mental disorders diminished across increasing age groups of men and women. Women aged 55-59, 65-69, and 70-74 had significantly lower rates of mental disorders than those aged 45-49. In contrast, only men aged 65-69 and 70-74 demonstrated significantly lower prevalence compared with men aged 45-49. Amongst younger men, retirees were significantly more likely to have a common mental disorder relative to men still in the labour force; however, this was not the case for retired men of, or nearing, the traditional retirement age of 65. Men and women with poor physical health were also more likely to have a diagnosable mental disorder. The findings of this study indicate that, for men, the relationship between retirement and mental health varies with age. The poorer mental health of men who retire early is not explained by usual risk factors. Given current policy changes in many countries to curtail early retirement, these findings highlight the need to consider mental health, and its influencing factors, when encouraging continued employment amongst older adults.

Decline in Common Mental Disorder prevalence in men during the sixth decade of life. Evidence from the National Psychiatric Morbidity Survey.

BACKGROUND: The impact of social transitions that might improve mental health, such as retirement, has attracted limited attention. Adverse occupational conditions and involuntary exit from work are linked to high rates of common mental disorders, but voluntary retirement is associated with improved mental health. AIMS: We aimed to estimate the prevalence of common mental disorders around the conventional retirement age and to identify the associated factors that might explain differences in rates. METHODS: Data were from the Psychiatric Morbidity Survey of Great Britain (2000), covering a sample of 8,580 respondents aged 16-74 years. Current common mental (neurotic) disorder presence was based on the revised Clinical Interview Schedule. RESULTS: Prevalence rates for having any common mental disorder in men aged 65-69 years (5%; 95% CI: 2.7-7.3) were dramatically lower than in the agegroup 60-64 years (14.5%; 95 % CI: 10.6-18.5). This pattern applied to individual disorders and to the prevalence of very high symptoms counts. Prevalence rates in women peaked at age 50 and declined thereafter, but no large changes in prevalence are evident around age 60 or 65 years. In men leaving work early (aged 50-64 years), prevalence of common mental disorders remains high until the conventional retirement age. There is little change in exposure to other studied risk factors capable of explaining prevalence reduction, with the exception of decreased economic hardship in the older group. CONCLUSION: In the general population aged 50-74 years,there is a dramatic improvement in mental health in men after the conventional retirement age, but not in women. In men who leave work earlier, prevalence remains relatively high until after age 65.