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OBJECTIVES: Studies of public health reporting have only examined multiple episodes of the same communicable disease within an individual. We aimed to characterize Montreal residents with multiple reportable disease episodes from 1990 to 2012, while accounting for all types of reportable diseases. STUDY DESIGN: Retrospective cohort study. METHODS: We performed an exploratory analysis using descriptive statistics, contingency tables, and logistic regression. RESULTS: There were 157,839 individuals with at least one disease report and a total of 179,455 disease reports. The 9.8% of subjects with more than one episode accounted for 20.7% of all reported episodes. Among subjects with four or fewer episodes, 54.0% were women, while 74.3% of subjects with five or more episodes were men. Subjects with multiple episodes were more likely to be reported for sexually transmitted infections than were persons with a single episode [difference of proportions: 10.4% (95% CI: 10.0%-10.9%)] and to reside in the neighbourhood encompassing Montreal's gay village. CONCLUSIONS: Individuals with multiple communicable disease reports place a large burden on public health officials. These results may help guide investigation and prevention efforts to reduce the number of excess episodes.
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Enfermedades Transmisibles/epidemiología , Notificación Obligatoria , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Canadá/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Distribución por Sexo , Enfermedades de Transmisión Sexual/epidemiología , Adulto JovenRESUMEN
We identified an MSH6 mutation (c.10C>T, p.Gln4*) causing Lynch syndrome (LS) in 11 French Canadian (FC) families from the Canadian province of Quebec. We aimed to investigate the molecular and clinical implications of this mutation among FC carriers and to assess its putative founder origin. We studied 11 probands and 27 family members. Additionally 6433 newborns, 187 colorectal cancer (CRC) cases, 381 endometrial cancer (EC) cases and 179 additional controls, all of them from Quebec, were used. Found in approximately 1 of 400 newborns, the mutation is one of the most common LS mutations described. We have found that this mutation confers a greater risk for EC than for CRC, both in the 11 studied families and in the unselected cases: EC [odds ratio (OR) = 7.5, p < 0.0001] and CRC (OR = 2.2, p = 0.46). Haplotype analyses showed that the mutation arose in a common ancestor, probably around 430-656 years ago, coinciding with the arrival of the first French settlers. Application of the results of this study could significantly improve the molecular testing and clinical management of LS families in Quebec.
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Neoplasias Colorrectales Hereditarias sin Poliposis/epidemiología , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Proteínas de Unión al ADN/genética , Etnicidad/genética , Efecto Fundador , Mutación , Adolescente , Adulto , Anciano , Canadá/epidemiología , Niño , Preescolar , Neoplasias Colorrectales Hereditarias sin Poliposis/diagnóstico , Neoplasias Endometriales/epidemiología , Neoplasias Endometriales/genética , Familia , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Heterocigoto , Humanos , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , Quebec , Riesgo , Adulto JovenRESUMEN
BACKGROUND: Sleep lines are caused by individual's sleeping positions and should be differentiated from expression wrinkles. OBJECTIVE: The aim of the study was to investigate possible risk factors for sleep lines on a sizeable sample of middle-aged Caucasian women. METHODS: This study involved a sample of 542 French middle-aged women (44 to 70 years old) from Paris area. Three standardized facial photographs (face and profiles) were examined independently by two dermatologists allowing the identification of sleep lines and the evaluation of the severity of several facial skin features. Possible impacts of MC1R gene polymorphisms were tested using logistic regression models. RESULTS: Sixty women (11%) had facial sleep lines and showed generally more than one sleep line. The sleep lines were often located on the forehead, along the nose, on the cheeks and under the eyes, and more rarely on the chin. As expected, the sleep lines were associated with age, and the women with sleep lines showed also more severe signs of skin ageing. After adjustment on possible confounders, the presence of two major diminished function variants of the MC1R gene was identified as a strong risk factor for sleep lines [adjusted odds ratios (AOR) (95% CI): 8.25 (2.62-25.97)]. DISCUSSION/CONCLUSION: The data in the literature are scarce and this study is the first to be conducted on a sizeable sample of women. Our results suggest that genetic variations of MC1R are important determinants of the development of sleep lines.
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Receptor de Melanocortina Tipo 1/genética , Envejecimiento de la Piel/genética , Población Blanca , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Polimorfismo Genético , Factores de RiesgoRESUMEN
OBJECTIVES: Ageing leads to characteristic changes in the appearance of facial skin. Among these changes, we can distinguish the skin topographic cues (skin sagging and wrinkles), the dark spots and the dark circles around the eyes. Although skin changes are similar in Caucasian and Chinese faces, the age of occurrence and the severity of age-related features differ between the two populations. Little is known about how the ageing of skin influences the perception of female faces in Chinese women. The aim of this study is to evaluate the contribution of the different age-related skin features to the perception of age and attractiveness in Chinese women. METHODS: Facial images of Caucasian women and Chinese women in their 60s were manipulated separately to reduce the following skin features: (i) skin sagging and wrinkles, (ii) dark spots and (iii) dark circles. Finally, all signs were reduced simultaneously (iv). Female Chinese participants were asked to estimate the age difference between the modified and original images and evaluate the attractiveness of modified and original faces. RESULTS: Chinese women perceived the Chinese faces as younger after the manipulation of dark spots than after the reduction in wrinkles/sagging, whereas they perceived the Caucasian faces as the youngest after the manipulation of wrinkles/sagging. Interestingly, Chinese women evaluated faces with reduced dark spots as being the most attractive whatever the origin of the face. The manipulation of dark circles contributed to making Caucasian and Chinese faces being perceived younger and more attractive than the original faces, although the effect was less pronounced than for the two other types of manipulation. CONCLUSION: This is the first study to have examined the influence of various age-related skin features on the facial age and attractiveness perception of Chinese women. The results highlight different contributions of dark spots, sagging/wrinkles and dark circles to their perception of Chinese and Caucasian faces.
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Cara/fisiología , Percepción/fisiología , Envejecimiento de la Piel/fisiología , Factores de Edad , Pueblo Asiatico , Femenino , Humanos , Persona de Mediana Edad , Distribución Aleatoria , Estadísticas no Paramétricas , Población BlancaRESUMEN
BACKGROUND: To date, few epidemiological data on the relationships between solar lentigines, freckles and behavioural and constitutional risk factors in Caucasian populations exist. OBJECTIVES: To investigate the potential impact of behavioural and phenotypic variables, as well as the MC1R genetic background, on the history of facial freckles and the severity of solar lentigines in Caucasian women. METHODS: The severity of solar lentigines was graded from facial digital images of 523 French middle-aged women by a dermatologist and summarized by a score afterwards. The history of facial freckles was assessed and the sun-exposure behaviour was characterized using a six-category typology. Risk factors including MC1R polymorphism were evaluated using logistic regression models. RESULTS: Two constitutive host factors were found to be independently associated with a history of facial freckles: frequent sunburns and the presence of diminished function variants of the MC1R gene. In addition to age, five factors were independently associated with solar lentigines: constitutive host factors (dark skin colour and tanning capacity), a history of freckles, sun-exposure behaviour and current intake of oral contraceptive or progestogen treatments. CONCLUSION: These results strengthen the hypothesis that solar lentigines are markers of photoaging, whereas freckles are mainly determined by genetic factors. The finding that hormonal treatment is associated with a higher risk for solar lentigines merits further investigations.
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Lentigo/epidemiología , Melanosis/epidemiología , Luz Solar , Adulto , Anciano , Canadá/epidemiología , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Receptor de Melanocortina Tipo 1/genética , Factores de RiesgoRESUMEN
BACKGROUND: Atopic dermatitis (AD) is associated with null mutations in the filaggrin (FLG) gene. OBJECTIVE: To assess the impact of FLG null mutations on biophysical properties and the molecular composition of the stratum corneum (SC) in healthy individuals and AD patients. METHODS: A total of 196 French adults, including 97 with a history of mild to moderate AD, were genotyped for the three major European FLG mutations. Components of the natural moisturizing factor (NMF), lipids and water content in the SC were determined using Raman spectroscopy. In addition, trans-epidermal water loss, capacitance and pH of the SC were measured. RESULTS: Stratum corneum concentrations of total NMF, water, ornithine and urocanic acid (UCA) were significantly lower in AD patients than in healthy controls. Null mutations of FLG were detected in 4% of controls and 10% of AD patients. FLG mutations were associated with increased SC levels of lactate, reduced concentrations of most other NMF components and higher disease severity in AD patients. In AD patients without FLG mutations, the content of NMF constituents decreased with increasing disease severity. The concomittant presence of low concentrations of histidine, alanine and either glycine or pyrrolidone-5-carboxylic acid (PCA) in the SC was associated with FLG mutations with 92% specificity. CONCLUSIONS: Our findings suggest a low prevalence of FLG mutations in mild AD and support an important role for filaggrin in determining the physicochemical parameters of the SC. The combined measurement of several filaggrin breakdown products in the SC may be useful to specifically predict the presence of FLG mutations.
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Dermatitis Atópica/patología , Epidermis/patología , Proteínas de Filamentos Intermediarios/genética , Mutación , Espectrometría Raman/métodos , Adulto , Secuencia de Bases , Biofisica , Estudios de Casos y Controles , Cartilla de ADN , Dermatitis Atópica/genética , Femenino , Proteínas Filagrina , Genotipo , Humanos , MasculinoRESUMEN
BACKGROUND: Despite increasing demands for decorative tattooing in people of all ages, occupations and social classes, little is known regarding individuals' characteristics and behaviour with respect to tattooing. OBJECTIVE: The objective was to describe a large sample of French people asking for tattoo laser removal, to investigate their reasons for being tattooed and for tattoo removal, and to identify groups of subjects sharing similar characteristics. METHODS: A prospective exploratory study was conducted on 151 consecutive subjects asking for tattoo removal. RESULTS: The study population was composed of 65 women and 86 men, aged between 18 and 60 years. The reasons mentioned for tattoo removal included aesthetic, social, employment, family or partner pressure, change of lifestyle or partner and incompatibility with present attitudes and values. Four profiles were identified. Types 1 and 3 correspond to subjects with amateur tattoos more frequently reporting social reasons for tattoo removal, whereas types 2 and 4 correspond to subjects with studio tattoos who more frequently report aesthetic reasons. Types 1 and 4 are mainly composed of men (aged over forty and under forty, respectively), type 2 of women under thirty and type 3 of subjects of either sex aged over forty. CONCLUSIONS: These profiles could be used to target information campaigns about tattooing and tattoo removal techniques to avoid unwanted tattoos, and afterwards, possible disappointment after removal, as well as to target education programs on possible health risks. Furthermore, our findings open the way to focus further studies on more homogenous group of tattooed subjects.
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Tatuaje/psicología , Tatuaje/tendencias , Adolescente , Adulto , Actitud , Recolección de Datos , Empleo/psicología , Estética/psicología , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: The objective of this study was to assess the association between melanocortin-1 receptor (MC1R) variants and the severity of facial skin photoaging. METHODS: The study population comprised 530 French middle-aged women between 44 and 70 years. A trained dermatologist graded the severity of facial skin photoaging from photographs using Larnier's global scale. Logistic regressions were performed to assess the influence of MC1R polymorphism on severe photoaging (grades 1-3 vs. 4-6), with adjustment for possible confounders (demographic and phenotypic data, and sun exposure intensity). RESULTS: Overall, 35% of the women were wild-type homozygotes, 49% had one variant, 15% had two variants, and 1% had at least one rare variant. After adjustment for possible confounders, the presence of two major diminished function variants was found to be a risk factor for photoaging (adjusted odds ratio=5.61; 95% confidence interval [1.43-21.96]). DISCUSSION: Our results suggest that genetic variations of MC1R are important determinants for severe photoaging.
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Polimorfismo Genético , Receptor de Melanocortina Tipo 1/genética , Envejecimiento de la Piel/genética , Adulto , Factores de Edad , Anciano , Factores de Confusión Epidemiológicos , Femenino , Francia , Predisposición Genética a la Enfermedad , Genotipo , Hábitos , Humanos , Persona de Mediana Edad , Fenotipo , Pigmentación , Receptor de Melanocortina Tipo 1/fisiología , Factores de Riesgo , Envejecimiento de la Piel/efectos de la radiación , Luz SolarRESUMEN
BACKGROUND: Melasma is a frequent cause of consultations at dermatology departments by dark-skinned patients in Tunisia. OBJECTIVE: To investigate factors that influence melasma severity in a large Tunisian population. METHODS: A total of 197 patients (188 women and 9 men), who attended Tunis Military Hospital for a consultation were included prospectively from August 2005 to August 2006. Disease severity was estimated using the Melasma Area and Severity Index (MASI). Aggravating factors were investigated using multiple logistic regressions. RESULTS: Of the women included, 14% presented phototype III, 45% phototype IV and 41% phototype V; 76% presented a centrofacial melasma phenotype, 23% a malar and 1% a mandibular phenotype. About 60% developed melasma before thirty. Sun exposure was reported as a triggering factor by 51% of women and as an aggravating factor by 84%. Pregnancy was reported as an aggravating factor by 51% of women who had been pregnant, and oral contraceptive use reported by 38% of women exposed to oral contraceptives. The risk of severe melasma was about three times higher for women with age at onset under 30, phototype V and major lifetime sun exposure and about 8 times higher for women exposed to oral contraceptives. CONCLUSION: This study identifies a number of factors associated with the severity of melasma. Further epidemiological studies in this type of population, in particular, to investigate triggering factors, are justified by the aesthetic damage caused by melasma in dark-skinned patients, lack of efficacy of existing treatments, non-compliance with photoprotection recommendations and the challenge of treatment.
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Melanosis/epidemiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , TúnezRESUMEN
The role of targeted therapies in the treatment of women with breast cancer has been rapidly evolving. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), was the first HER2-targeted therapy that clearly demonstrated a significant clinical benefit for women with HER2-overexpressing metastatic breast cancer (mbc). However, in recent years it has become increasingly apparent that, when trastuzumab is used in the first-line setting in combination with chemotherapy, most women eventually develop progressive disease. Determining the treatment options available to women who have progressed while on trastuzumab therapy has been hampered by a paucity of high-quality published data. In addition, with the standard use of trastuzumab in the adjuvant setting (for eligible HER2-positive patients), the role of anti-HER2 agents for patients who experience a breast cancer relapse has become a clinically relevant question. This manuscript reviews current available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other HER2-targeted agents in two key mbc indications:Treatment for women with HER2-positive mbc progressing on trastuzumab (that is, treatment beyond progression)Treatment for women with HER2-positive mbc recurring following adjuvant trastuzumab (that is, re-treatment)The suggestions set out here will continue to evolve as data and future trials with trastuzumab and other HER2-targeted agents emerge.
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Because of the constant threat posed by emerging infectious diseases and the limitations of existing approaches used to identify new pathogens, there is a great demand for new technological methods for viral discovery. We describe herein a DNA microarray-based platform for novel virus identification and characterization. Central to this approach was a DNA microarray designed to detect a wide range of known viruses as well as novel members of existing viral families; this microarray contained the most highly conserved 70mer sequences from every fully sequenced reference viral genome in GenBank. During an outbreak of severe acute respiratory syndrome (SARS) in March 2003, hybridization to this microarray revealed the presence of a previously uncharacterized coronavirus in a viral isolate cultivated from a SARS patient. To further characterize this new virus, approximately 1 kb of the unknown virus genome was cloned by physically recovering viral sequences hybridized to individual array elements. Sequencing of these fragments confirmed that the virus was indeed a new member of the coronavirus family. This combination of array hybridization followed by direct viral sequence recovery should prove to be a general strategy for the rapid identification and characterization of novel viruses and emerging infectious disease.
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Genes Virales , Técnicas Genéticas , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Secuencia de Bases , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/virología , Genoma Viral , Humanos , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Análisis de Secuencia de ADN , Síndrome Respiratorio Agudo Grave/genéticaRESUMEN
PURPOSE: The aim of this study was to test the influence of phototype and vitamin D status feature on the bone mineral density (BMD) of the femoral neck in a group of middle-aged women considered at risk of osteoporosis (low levels of vitamin D [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL]). METHODS: This two-step study was conducted on 122 French women enrolled in the SUVIMAX (supplémentation en vitamines et minéraux antioxydants: antioxidant vitamin and mineral supplementation) cohort. The impact of various variables on BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun exposure intensity and phototype was investigated using regression models. RESULTS: No statistical link was found between BMD and the variables documenting vitamin D status and parathormone levels, nor phototype. Nevertheless, fair phototypes tended to be associated with lower BMD values. However, BMD decreased with age and increased with BMI and physical activity level. CONCLUSIONS: Whatever their phototype, adult women concerned about precarious vitamin D status should undergo a vitamin D supplementation in combination with an adequate calcium intake all year long and a proper sun protection. Moreover, a physical activity maintenance should provide an additional benefit for prevention of osteoporosis.
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Densidad Ósea , Osteoporosis Posmenopáusica/fisiopatología , Luz Solar , Vitamina D/fisiología , Calcitriol/sangre , Clima , Femenino , Francia , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/epidemiología , Medición de Riesgo , Tiempo (Meteorología)RESUMEN
PURPOSE: To assess whether prechemotherapy health-related quality-of-life (HQL) variables are associated with postchemotherapy nausea and vomiting (PCNV), and to determine their relationship to patient and treatment variables. PATIENTS AND METHODS: Eight hundred thirty-two chemotherapy-naive patients scheduled to receive antiemetic regimens containing a 5-hydroxytryptamine (5-HT3) antagonist with or without dexamethasone for moderately or highly emetogenic chemotherapy were enrolled. HQL was measured by the self-report European Organization for Research and Treatment of Cancer (EORTC) Care Quality of Life Questionnaire (QLQ-C30) within 7 days before chemotherapy. Prechemotherapy HQL scores, as well as other patient, disease, and treatment variables were compared in the groups of patients who had PCNV and those who did not have PCNV. All variables were assessed initially in a univariate analysis and then together in a multivariate analysis using step-wise logistic regression. The final model generated by the multivariate analyses was used in a risk factor analysis to predict PCNV. RESULTS: Univariate analyses identified 10 HQL variables and five patient and treatment characteristics that were associated with PCNV. In the multivariate analysis, the variables remaining in the final model included low social functioning, prechemotherapy nausea, female gender, highly emetogenic chemotherapy, and the lack of maintenance antiemetics (5-HT3 antagonists with or without dexamethasone) after chemotherapy. A history of low alcohol use was also associated with PCV, whereas increased fatigue and lower performance status were associated with PCN. In the risk factor analysis, the incidence of PCV increased from 20% in those having no risk factors to 76% in those having any four of the six risk factors. CONCLUSION: Several pretreatment HQL, patient, and treatment characteristics are associated with the occurrence of PCNV. Patients about to receive moderately or highly emetogenic chemotherapy should be screened for these factors and additional measures, such as behavior modification and modification of antiemetic therapy, should be considered in attempts to improve the control of PCNV.
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Antineoplásicos/efectos adversos , Estado de Salud , Náusea/psicología , Calidad de Vida , Vómitos/psicología , Análisis de Varianza , Femenino , Humanos , Incidencia , Relaciones Interpersonales , Masculino , Registros Médicos , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/epidemiología , Factores de Riesgo , Factores Sexuales , Vómitos/inducido químicamente , Vómitos/epidemiologíaRESUMEN
PURPOSE: We conducted a population-based study in Quebec, Canada, to assess longitudinal changes in systemic adjuvant therapy for node-negative breast cancer. MATERIALS AND METHODS: A stratified random sample was selected among women with newly diagnosed node-negative breast cancer in 1988, 1991, and 1993. Information on the patient, her tumor, source of care, and treatment was abstracted from medical charts. Patients were classified as being at minimal, moderate, or high risk of recurrence on the basis of criteria proposed at the 4th International Conference on Adjuvant Therapy of Primary Breast Cancer (St. Gallen, Switzerland, 1992), and systemic adjuvant treatment received was dichotomized as being consistent or not consistent with consensus recommendations. RESULTS: Overall, 1,578 cases of invasive breast carcinoma were reviewed. The proportion of patients who were given hormonal or cytotoxic treatment increased from 51.7% to 73.1% from 1988 to 1993. Virtually all women at minimal risk were treated in 1991 and 1993 according to the consensus statement. The proportions of women so treated were 75.0% and 65.4% in the moderate- and high-risk categories, respectively, in 1991. In 1993, these proportions were 71.4% and 67.0%, respectively. Omission of chemotherapy, especially in high-risk women with estrogen receptor-negative tumors who were 50 to 69 years of age, was the most frequent inconsistency with guidelines. CONCLUSION: Systemic adjuvant therapy for node-negative breast cancer has gained acceptance. Better understanding of the decision-making process, of the perception of the risks and benefits involved, and of the impact of alternative strategies for the dissemination of consensus recommendations are needed to promote the use of chemotherapy in specific categories of women who are at high risk of recurrence.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante/tendencias , Anciano , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Femenino , Guías como Asunto , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Receptores de Estrógenos/análisis , Tamoxifeno/uso terapéuticoRESUMEN
PURPOSE: This study examines whether the schedule of ondansetron significantly influences its antiemetic efficacy in the first 24 hours after chemotherapy, whether the administration of oral ondansetron after 24 hours is effective in preventing delayed emesis, and whether the efficacy of ondansetron is preserved over multiple courses of moderately emetogenic chemotherapy. PATIENTS AND METHODS: A multicenter double-blind study randomized 302 cancer patients to one of three treatment arms. Arm A received dexamethasone 10 mg intravenously (i.v.) plus ondansetron (Zofran; Glaxo Canada Inc, Toronto, Canada) 8 mg i.v. prechemotherapy plus ondansetron 8 mg orally every 12 hours postchemotherapy for nine doses. Arm B received dexamethasone 10 mg i.v. plus ondansetron 16 mg i.v. prechemotherapy plus placebo orally postchemotherapy in the same schedule as arm A. Arm C received dexamethasone 10 mg i.v. plus ondansetron 8 mg prechemotherapy plus ondansetron 8 mg orally postchemotherapy for one dose followed by placebo orally every 12 hours for eight more doses. Response was assessed by the number of reported episodes of vomiting and by severity of nausea measured on a visual analog scale (VAS). RESULTS: The two schedules of ondansetron used in the first 24 hours were no different in their antiemetic efficacy, with similar rates for complete responses (76.7% v 72.0%, P = .472), complete plus major responses (90.2% v 82.0%, P = .135), and severity of nausea (P = .348). Oral ondansetron after 24 hours was more effective than placebo in preventing delayed nausea and emesis, with superior rates of complete responses (59.6% v 42.1%, P = .012 by one-sided test), complete plus major responses (80.9% v 66.3%, P = .018 by one-sided test), and less severe nausea (9.2 mm v 18.6 mm on a 100-mm VAS, P = .002). The efficacy of ondansetron was maintained over subsequent courses of chemotherapy. CONCLUSION: The schedule of ondansetron in the first 24 hours does not influence its efficacy. The use of oral maintenance ondansetron is effective in preventing delayed maintenance ondansetron is effective in preventing delayed nausea and emesis after moderately emetogenic chemotherapy.
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Antineoplásicos/efectos adversos , Dexametasona/administración & dosificación , Náusea/prevención & control , Ondansetrón/administración & dosificación , Vómitos/prevención & control , Antineoplásicos/administración & dosificación , Dexametasona/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Ondansetrón/uso terapéutico , Calidad de Vida , Vómitos/inducido químicamenteRESUMEN
PURPOSE: To define the maximum-tolerated dose, recommended phase II dose (RD), dose-limiting toxicity (DLT), and pharmacokinetics of a novel taxane, RPR 109881A, administered on days 1 and 8 of a 21-day cycle. PATIENTS AND METHODS: Twenty-nine patients were enrolled and treated according to a modified continual reassessment method from a starting dose of 7.5 mg/m(2) to 52.5 mg/m(2). Detailed pharmacokinetic analyses of blood and urine were performed on days 1 and 8 of the first cycle. Toxicity was monitored weekly. RESULTS: DLT consisting of grade 3 or 4 diarrhea was seen in three of six patients at 52.5 mg/m(2). Grade 3 or 4 granulocytopenia was also seen in five of six patients treated at this dose (four of six in the first cycle). At the next lower dose level, 45 mg/m(2) toxicity was moderate, with only one of 12 patients experiencing severe diarrhea and grade 4 granulocytopenia with associated infection. Drug concentrations were consistent with a three-compartment open model. The total-body clearance suggests a linear dose-concentration relationship. RPR 109881A has a high clearance (mean, 42.6 L/h/m(2)), a large volume of distribution (mean, 952 L/m(2)), and a long terminal half-life (mean, 24 hours). There was no drug accumulation between days 1 and 8. One partial response was seen in a patient with renal cell carcinoma. CONCLUSION: The RD of RPR 109881A given as a 1-hour infusion on days 1 and 8 of a 21-day cycle is 45 mg/m(2). At this dose the drug is well tolerated and should be further studied.
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Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Neoplasias/tratamiento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Taxoides , Adulto , Anciano , Agranulocitosis/inducido químicamente , Antineoplásicos Fitogénicos/farmacocinética , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias/metabolismoRESUMEN
PURPOSE: Bone metastases are a major cause of morbidity in breast cancer, resulting in complications that include pain, loss of mobility, pathologic fracture, and tumor-induced hypercalcemia (TIH). Inhibition of osteoclast-mediated bone destruction using bisphosphonates represents a promising new management approach. PATIENTS AND METHODS: Breast cancer patients with bone metastases were randomly allocated to receive chemotherapy alone (152 patients) or chemotherapy plus pamidronate 45 mg in 250 mL of saline as a 1-hour intravenous infusion every 3 weeks (143 patients). Whenever possible, treatment continued until progression of disease (PD) in bone appeared on radiographs or bone scan. Time to PD in bone and pain reduction according to a self-assessment six-point scale were selected as primary end points. PD in bone was verified during extramural review (EMR) of all imaging studies by blinded observers, and these data were used as the main efficacy criterion. Analgesic intake, World Health Organization (WHO) performance status, and complications of bone metastases (radiotherapy, TIH, fractures, orthopedic surgery) were also compared in the two groups. RESULTS AND CONCLUSION: At EMR, median time to PD in bone was increased by 48% in patients who received pamidronate (249 v 168 days; P = .02, Wilcoxon test). Marked pain relief, defined as a two-point decrease lasting for > or = 6 weeks, was reported by 44% of pamidronate patients and by 30% of controls (P = .025, chi 2 test). The infusions (median, nine per patient; range, 0 to 39) were well tolerated, with no major toxicities reported. Pamidronate by repeated infusion can significantly slow the progression of bone metastases and reduce attendant morbidity.
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Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Difosfonatos/administración & dosificación , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Óseas/sangre , Neoplasias Óseas/patología , Calcio/sangre , Difosfonatos/efectos adversos , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , PamidronatoRESUMEN
PURPOSE: This phase III study was performed to determine the superiority of doxorubicin (DOX) and vinorelbine (VNB) (arm 1) versus DOX alone (arm 2) in metastatic breast cancer (MBC) for overall survival (OS), time to treatment failure (TTF), toxicity, and quality of life (QOL). PATIENTS AND METHODS: Three hundred three patients were randomized to DOX 50 mg/m(2) intravenously (IV) on day 1 and VNB 25 mg/m(2) IV on days 1 and 8 (arm 1) or DOX 70 mg/m(2) IV on day 1 (arm 2). Both regimens were given every 3 weeks until a cumulative DOX dose of 450 mg/m(2). After 16 of the first 65 randomized patients experienced febrile neutropenia (FN), the doses were reduced to DOX 40 mg/m(2) on day 1 and VNB 20 mg/m(2) on days 1 and 8 versus DOX 60 mg/m(2) on day 1. Eligible patients were vinca alkaloid and anthracycline naive. Chemotherapy was first-line or second-line for MBC. RESULTS: Three patients were ineligible. Thus, 300 patients were assessable for toxicity and to determine time to disease progression (TTP), TTF, and OS. Two hundred eighty-nine patients were assessable for response, and 99 responders were assessable for response duration (RD). The response rates, QOL, and median RD, TTP, and TTF were not significantly different between the arms. Median OS was 13.8 months for arm 1 versus 14.4 months for arm 2 (P =.4). Grade 3 or 4 granulocytopenia was equivalent in both arms but more grade 3/4 neurotoxicity, mild venous toxicity, and FN were seen on arm 1. CONCLUSION: The survival with DOX and VNB is not superior to DOX alone in MBC.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Vinblastina/análogos & derivados , Adulto , Anciano , Antineoplásicos Fitogénicos/efectos adversos , Neoplasias de la Mama/patología , Progresión de la Enfermedad , Doxorrubicina/efectos adversos , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Calidad de Vida , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , VinorelbinaRESUMEN
PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.
Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Dexametasona/uso terapéutico , Granisetrón/uso terapéutico , Antagonistas de la Serotonina/uso terapéutico , Vómitos/prevención & control , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/prevención & control , Estadísticas no Paramétricas , Vómitos/inducido químicamenteRESUMEN
151 patients (149 evaluable) receiving their first course of chemotherapy containing cisplatin in a dose of at least 50 mg/m2 were randomised to receive either a single dose of intravenous granisetron 80 micrograms/kg or intravenous metoclopramide 2 mg/kg every 2 h for five doses plus a single dose of dexamethasone 10 mg and diphenhydramine. After 24 h, there was no significant difference between groups with respect to nausea or vomiting: in the granisetron group 46% of patients had no emesis, versus 44% of the standard group. Granisetron is an antiemetic agent with efficacy similar to that of high-dose metoclopramide plus dexamethasone.