RESUMEN
OBJECTIVE: Although common in psychiatric practice, reasons for antipsychotic polypharmacy (APP) have remained unclear. METHODS: Single-site, semi-structured interview study of prescribers at a psychiatric teaching hospital inquiring about APP attitudes and behaviors, including frequency, preferred combinations, rationale and concerns. RESULTS: Forty-four prescribers reported using APP in 17.0 ± 10.0% of antipsychotic-treated patients. Although clinicians themselves initiated APP in only 23.3 ± 27.0% of cases, they did not attempt conversion to antipsychotic monotherapy in 40.9 ± 37.7%, despite reported successful conversion in 28.0 ± 30.8% of cases. The following reasons justified most APP (0-10): cross-titration (9.2 ± 1.4), failed clozapine trial (8.2 ± 2.2), randomized controlled evidence (8.0 ± 2.0), and clozapine intolerance (7.7 ± 2.6). Prescribers felt "moderately" (5.0 ± 1.9) concerned about APP (0-10), mostly due to chronic side effects (7.6 ± 2.0), lack of evidence (7.1 ± 2.2), non-adherence risk (6.7 ± 2.3) and mortality risk (6.7 ± 3.2), while increased cost (4.9 ± 2.5) and higher total antipsychotic dose (4.2 ± 2.9) ranked lowest. Comparing high with low APP prescribers (>10% vs. ≤ 10% of patients; mean: 36.1 ± 19.8 vs. 3.4 ± 3.4, p<0.0001), no differences emerged on 25/26 ratings regarding APP justification and 9/9 ratings regarding concerns. In a multivariate analyses, only attending status (OR=10.3, p=0.0043) and endorsing a specific APP preference (OR=21.4, p=0.011) predicted APP use >10% (r(2):0.35, p<0.0001), yet no uniformly preferred APP strategy emerged. CONCLUSIONS: High APP prescribers had more clinical experience, less concerns about APP and more likely a preferred APP choice, although no overall preferred strategy emerged. Otherwise, high and low APP prescribers shared attitudes toward APP. Both had inherited most of their APP cases and were reluctant to convert patients to antipsychotic monotherapy.
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Antipsicóticos/uso terapéutico , Actitud , Conocimiento , Trastornos Mentales/tratamiento farmacológico , Médicos/psicología , Polifarmacia , Femenino , Encuestas Epidemiológicas , Humanos , Entrevista Psicológica , Masculino , Análisis Multivariante , Medicamentos bajo Prescripción/uso terapéutico , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Osteopontin has been suggested as a marker of disease progression in patients with melanoma because of its overexpression in recent microarray analyses. However, its prognostic role in melanoma has not been fully defined. METHODS: Osteopontin expression status was examined using immunohistochemical analysis of a tissue microarray that contained primary cutaneous melanomas from 345 patients. The correlation between osteopontin expression and several histologic markers for melanoma was assessed by using the Chi-square test and the Le directional test. The impact of osteopontin expression on recurrence-free survival (RFS) and disease-specific survival (DSS) of patients with melanoma was examined using Cox regression and Kaplan-Meier analyses. The impact of increasing osteopontin expression on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS: High osteopontin expression was associated with increased tumor thickness (P = .037), Clark level (P = .035), and mitotic index (P = .046). Kaplan-Meier analysis demonstrated an association between osteopontin expression and reduced RFS (P < .03) and DSS (P = .05). Multivariate Cox regression analysis demonstrated that high osteopontin immunostaining had an independent impact on the DSS of this melanoma cohort (P = .049). In addition, osteopontin expression was significantly predictive of SLN metastasis (P = .009) and SLN burden, as assessed by the mean number of SLN metastases (P = .0025). Multivariate logistic regression analysis demonstrated an independent role for osteopontin expression in predicting SLN status (P = .0062). CONCLUSIONS: The current results validated the role of osteopontin as an independent prognostic marker for melanoma and provided new evidence for its predictive role in melanoma lymph node metastasis.
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Melanoma/diagnóstico , Osteopontina/análisis , Neoplasias Cutáneas/diagnóstico , Biomarcadores/análisis , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Biopsia del Ganglio Linfático Centinela , Análisis de Matrices TisularesRESUMEN
Ulceration has been shown to be an adverse prognostic factor in primary cutaneous melanoma. However, the extent of ulceration required for histologic identification and biologic significance is unclear. We examined the impact of extent of ulceration on melanoma outcome in a cohort of 235 melanoma patients by evaluating the relationship between percentage of ulceration in the vertical growth phase of the primary tumor and 2 outcome parameters: sentinel lymph node status and overall survival. We measured the diameter of the ulcerated area in millimeters over the diameter of the entire vertical growth phase. There was a statistically significant relationship between increasing percentage of tumor ulceration and both sentinel lymph node status as well as overall survival, with a binary cut-off point of 2% for sentinel lymph node status and 5% for overall survival. The percentage of ulceration provides additional prognostic information in predicting sentinel lymph node status and in determining survival in melanoma patients. These results suggest that no more than minimal ulceration is required to have a prognostic impact on melanoma survival.
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Melanoma/patología , Neoplasias Cutáneas/patología , Úlcera/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Melanoma/mortalidad , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/mortalidad , Análisis de SupervivenciaRESUMEN
PURPOSE: To assess the prognostic significance of nuclear receptor coactivator-3 (NCOA3) overexpression in primary cutaneous melanoma. PATIENTS AND METHODS: NCOA3 expression was assessed using immunohistochemical analysis of a melanoma tissue microarray (TMA) containing primary melanomas from 343 patients with defined histology and follow-up. The impact of the presence or absence of various prognostic factors on relapse-free survival (RFS) and disease-specific survival (DSS) of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. The impact of presence or absence of various factors on sentinel lymph node (SLN) metastasis was assessed using logistic regression analysis. RESULTS: Increasing degree of NCOA3 expression was significantly predictive of SLN metastasis (P = .013) and the mean number of SLN metastases (P = .031). Kaplan-Meier analysis demonstrated a significant association between NCOA3 overexpression and reduced RFS (P = .021) and DSS (P = .030). Logistic regression analysis revealed increasing degree of NCOA3 expression to be an independent predictor of SLN status (P = .017). Multivariate Cox regression analysis showed the independent impact of NCOA3 expression on RFS (P = .0095) and DSS (P = .021). NCOA3 was the most powerful factor predicting DSS, outperforming tumor thickness and ulceration. CONCLUSION: These results identify NCOA3 as a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS, and DSS.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Histona Acetiltransferasas/biosíntesis , Histona Acetiltransferasas/genética , Melanoma/metabolismo , Neoplasias Cutáneas/metabolismo , Transactivadores/biosíntesis , Transactivadores/genética , Supervivencia sin Enfermedad , Humanos , Metástasis Linfática , Melanoma/diagnóstico , Melanoma/patología , Persona de Mediana Edad , Coactivador 3 de Receptor Nuclear , Análisis de Secuencia por Matrices de Oligonucleótidos , Pronóstico , Modelos de Riesgos Proporcionales , Recurrencia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the impact of microsatellites as a prognostic factor in primary cutaneous melanoma. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. Patients A total of 504 patients with a history of primary melanoma observed for 2 years or having experienced a first relapse. MAIN OUTCOME MEASURES: Overall survival (OS) and relapse-free survival (RFS). RESULTS: Forty-five patients had evidence of microsatellites in their primary melanoma. Presence of microsatellites significantly correlated with the presence of several other histologic high-risk factors such as tumor thickness, ulceration, Clark level, vascular factors, and mitotic rate. Univariate analysis demonstrated decreased RFS and OS in patients with microsatellites. Presence of microsatellites was associated with increased locoregional metastasis but not distant metastasis. In multivariate analysis, with the inclusion of 6 other clinical and histologic factors, presence of microsatellites was a significant predictor of RFS but not OS. Patients with clinical macrosatellites had a trend toward worsening OS compared with those with microsatellites. CONCLUSIONS: The presence of microsatellites is intimately tied to other markers of melanoma aggressiveness. Microsatellites appear to predict locoregional relapse and RFS but neither distant metastasis nor OS. These results may have implications for patient care as well as the inclusion of microsatellites in stage III of the current classification.
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Biomarcadores de Tumor/análisis , Melanoma/patología , Repeticiones de Microsatélite , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/patología , Análisis de Varianza , Biopsia con Aguja , Estudios de Cohortes , Femenino , Humanos , Inmunohistoquímica , Masculino , Melanoma/mortalidad , Melanoma/terapia , Análisis Multivariante , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Probabilidad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/terapia , Análisis de SupervivenciaRESUMEN
PURPOSE: To examine a model of melanoma progression based on vascular factors and the role of NF-kappa B in the vascular progression of melanoma. PATIENTS AND METHODS: A data set of 526 patients from the University of California San Francisco Melanoma Center with 2 years of follow-up or first relapse was studied. The impact of the presence or absence of various prognostic factors on overall survival of melanoma patients was assessed using Cox regression and Kaplan-Meier analysis. A matched-pair analysis of NF-kappa B expression was performed in cases with vascular involvement and increased tumor vascularity versus matched controls lacking these factors. RESULTS: Cox regression analysis of factors evaluated by the American Joint Committee on Cancer Melanoma Staging Committee reproduced the powerful impact of tumor thickness and ulceration in this data set. With the inclusion of vascular factors such as tumor vascularity and vascular involvement, ulceration was no longer significant in predicting overall survival. By multivariate analysis, vascular involvement and tumor vascularity were the strongest predictors of melanoma outcome. Tumor vascularity seems to be a precursor of both vascular involvement and ulceration. A matched-pair tissue array analysis demonstrated the significant correlation between overexpression of NF-kappa B-p65 and the development of vascular factors. CONCLUSION: Vascular factors play an important role in the progression of malignant melanoma. Ulceration may be a surrogate marker for the interactions between melanoma and the tumor vasculature. NF-kappa B seems to play an important role in the development of these factors.
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Biomarcadores de Tumor/metabolismo , Endotelio Vascular/patología , Melanoma/patología , FN-kappa B/metabolismo , Neovascularización Patológica , Neoplasias Cutáneas/patología , Estudios de Seguimiento , Humanos , Análisis por Apareamiento , Melanoma/irrigación sanguínea , Melanoma/mortalidad , Invasividad Neoplásica , Modelos de Riesgos Proporcionales , San Francisco/epidemiología , Neoplasias Cutáneas/irrigación sanguínea , Neoplasias Cutáneas/mortalidad , Análisis de SupervivenciaRESUMEN
Tumor thickness has historically been the single most important factor in risk assessment for stage I and II melanoma patients. However, it is possible to more accurately determine a patient's prognosis by also using other known prognostic indicators, such as ulceration, vascular invasion, and angiogenesis. A probabilistic approach to risk assessment has implications for the appropriate selection of treatment modalities, such as sentinel lymph node biopsy and re-excision margins. Each patient's risk for recurrence also has implications for which follow-up protocol would be most appropriate for the patient. Finally, those risk factors that repeatedly demonstrate an independent impact on prognosis should be used as stratification factors in adjuvant therapy trials.