RESUMEN
Androgen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18-36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.
Asunto(s)
Enfermedades Gastrointestinales/patología , Enfermedades Urogenitales Masculinas/patología , Metformina/efectos adversos , Neoplasias de la Próstata/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Persona de Mediana Edad , Pronóstico , Neoplasias de la Próstata/patologíaRESUMEN
PURPOSE: The purpose of the study is to evaluate the impact of validation on the identification of major bleeding events in The Health Improvement Network (THIN) database in patients receiving anticoagulant therapy. METHODS: Patients aged 2 to 89 years with a first prescription for an anticoagulant (rivaroxaban or warfarin) between 2012 and 2015 were identified in THIN. Major bleeding events, defined as bleeding events necessitating hospitalization or referral to accident and emergency services or a specialist clinic, were identified using a 2-step ascertainment process based on read codes only, and then validated using a 2-step process requiring manual review of patients' records. RESULTS: The positive predictive value for the ascertainment of major intracranial (IC) bleeds using only read codes was 96.9%, compared with 70.4% for gastrointestinal (GI) bleeds and 64.1% for urogenital (UG) bleeds. The incidence rate of major IC bleeding events was therefore similar when it was calculated before and after validation (0.32 per 100 person-years and 0.31 per 100 person-years, respectively). The incidence rate of major GI bleeds identified using read codes alone was reduced following validation from 2.05 to 0.94 per 100 person-years, and that of major UG bleeds decreased from 2.45 to 1.11 per 100 person-years. CONCLUSIONS: Major GI and UG bleeding events ascertained from THIN using read codes require validation using additional information to prevent outcome misclassification. The absence of validation may lead to overestimated incidence rates of major bleeding for GI and UG bleeds.
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Anticoagulantes/efectos adversos , Enfermedades Urogenitales Femeninas/epidemiología , Hemorragia Gastrointestinal/epidemiología , Hemorragias Intracraneales/epidemiología , Enfermedades Urogenitales Masculinas/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Enfermedades Urogenitales Femeninas/inducido químicamente , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/terapia , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/terapia , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Atención Primaria de Salud/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Factores de Riesgo , Rivaroxabán/efectos adversos , Estudios de Validación como Asunto , Warfarina/efectos adversos , Adulto JovenRESUMEN
Hydraulic-fracturing fluids and wastewater from unconventional oil and natural gas development contain hundreds of substances with the potential to contaminate drinking water. Challenges to conducting well-designed human exposure and health studies include limited information about likely etiologic agents. We systematically evaluated 1021 chemicals identified in hydraulic-fracturing fluids (n=925), wastewater (n=132), or both (n=36) for potential reproductive and developmental toxicity to triage those with potential for human health impact. We searched the REPROTOX database using Chemical Abstract Service registry numbers for chemicals with available data and evaluated the evidence for adverse reproductive and developmental effects. Next, we determined which chemicals linked to reproductive or developmental toxicity had water quality standards or guidelines. Toxicity information was lacking for 781 (76%) chemicals. Of the remaining 240 substances, evidence suggested reproductive toxicity for 103 (43%), developmental toxicity for 95 (40%), and both for 41 (17%). Of these 157 chemicals, 67 had or were proposed for a federal water quality standard or guideline. Our systematic screening approach identified a list of 67 hydraulic fracturing-related candidate analytes based on known or suspected toxicity. Incorporation of data on potency, physicochemical properties, and environmental concentrations could further prioritize these substances for future drinking water exposure assessments or reproductive and developmental health studies.
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Discapacidades del Desarrollo/inducido químicamente , Agua Potable/efectos adversos , Enfermedades Urogenitales Femeninas/inducido químicamente , Fracking Hidráulico , Aguas Residuales/toxicidad , Bases de Datos Factuales , Agua Potable/análisis , Agua Potable/normas , Femenino , Humanos , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Estados Unidos , United States Environmental Protection Agency , Calidad del Agua/normasAsunto(s)
Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Neoplasias/inducido químicamente , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Femenino , Enfermedades Urogenitales Femeninas/inducido químicamente , Hematuria/inducido químicamente , Humanos , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamenteRESUMEN
Cancer survivors often experience symptoms related to hormone deprivation, including vasomotor symptoms, genitourinary symptoms, and sexual health concerns. These symptoms can occur due to natural menopause in midlife women, or they can be brought on by oncologic therapies in younger women or men. We searched PubMed for English-language studies from January 1990 through January 2016 to identify relevant articles on the management of hormone deprivation symptoms, including vasomotor, genitourinary, and sexual symptoms in patients with cancer. The search terms used included hormone deprivation, vasomotor symptoms, hot flash, vaginal dryness, sexual dysfunction, and breast cancer. This manuscript provides a comprehensive description of data supporting the treatment of symptoms associated with hormone deprivation.
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Antineoplásicos/efectos adversos , Enfermedades Urogenitales Femeninas/inducido químicamente , Hormonas Esteroides Gonadales/deficiencia , Terapia de Reemplazo de Hormonas/efectos adversos , Enfermedades Urogenitales Masculinas/inducido químicamente , Neoplasias/complicaciones , Disfunciones Sexuales Fisiológicas/inducido químicamente , Sistema Vasomotor/efectos de los fármacos , Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Ansiolíticos/uso terapéutico , Antidepresivos/uso terapéutico , Antineoplásicos/uso terapéutico , Antagonistas Colinérgicos/uso terapéutico , Terapia Cognitivo-Conductual , Estrógenos/efectos adversos , Estrógenos/uso terapéutico , Femenino , Enfermedades Urogenitales Femeninas/terapia , Terapia de Reemplazo de Hormonas/normas , Sofocos/etiología , Sofocos/terapia , Humanos , Masculino , Enfermedades Urogenitales Masculinas/terapia , Neoplasias/dietoterapia , Progesterona/efectos adversos , Progesterona/análogos & derivados , Progesterona/uso terapéutico , Disfunciones Sexuales Fisiológicas/terapia , Sobrevivientes , Sistema Vasomotor/fisiopatologíaRESUMEN
BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric disorder that begins in childhood. Atomoxetine is a selective inhibitor of the presynaptic norepinephrine transporter. Several studies have demonstrated the safety and efficacy of atomoxetine in the treatment of ADHD. OBJECTIVE: The objective of this analysis was to provide additional information on the frequency, time to onset and time to resolution of sexual and genitourinary (GU) treatment-emergent adverse events (TEAEs) reported during atomoxetine treatment in clinical trials. METHODS: Data from all adult atomoxetine placebo-controlled ADHD trials were pooled for this analysis, for a total of 3,314 patients (atomoxetine, n = 1,738; placebo, n = 1,576). Additionally, data from all adolescent patients (baseline age ≥13 to <18 years) within all ADHD placebo-controlled trials were pooled for analysis, for a total of 538 patients (atomoxetine, n = 329; placebo, n = 209). Rates of sexual and GU TEAEs were summarized by sex for each age group. Time to onset and resolution of sexual and GU TEAEs were summarized and compared using Kaplan-Meier methods. RESULTS: Overall, the baseline characteristics of randomized patients in the atomoxetine and placebo groups were similar. Profiles of sexual and GU TEAEs for atomoxetine appeared clinically similar to placebo in female patients and in adolescent male patients. Adult male patients reported relatively more sexual and GU TEAEs when taking atomoxetine compared with placebo, with libido decreased (4.6 vs. 3.0 %), dysuria (3.7 vs. 1.5 %), urinary hesitation (6.9 vs. 2.4 %), urine flow decreased (2.5 vs. 0.6 %), ejaculation disorder (2.8 vs. 1.1 %) and erectile dysfunction (8.0 vs. 1.9 %) being the most common. The time to onset of the most common TEAEs in adult male patients tended to occur relatively early in dosing: within the first 2 weeks for GU TEAEs, and during the second and third week of dosing for erectile and ejaculation issues. The median time to resolution for these events ranged from around 3-8 weeks after event onset, depending on the event. While the common sexual and GU TEAEs showed numerically higher percentages of discontinuations in atomoxetine-treated patients compared with placebo, most incidences of the sexual and GU TEAEs were not considered severe. CONCLUSIONS: The sexual and GU TEAE profiles of patients taking atomoxetine were generally similar to those of patients taking placebo in the female and adolescent male populations, with greater frequency of TEAEs reported in adult males taking atomoxetine compared with placebo. The time to onset of the TEAEs tended to be shorter, and time to resolution tended to be longer in adult male patients treated with atomoxetine compared with those receiving placebo. The conclusions must be interpreted with caution because the TEAEs were likely underreported.
Asunto(s)
Inhibidores de Captación Adrenérgica/efectos adversos , Enfermedades Urogenitales Femeninas/inducido químicamente , Propilaminas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Disfunciones Sexuales Fisiológicas/inducido químicamente , Disfunciones Sexuales Psicológicas/inducido químicamente , Adolescente , Adulto , Anciano , Clorhidrato de Atomoxetina , Femenino , Enfermedades Urogenitales Femeninas/diagnóstico , Humanos , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Enfermedades Urogenitales Masculinas/diagnóstico , Persona de Mediana Edad , Disfunciones Sexuales Fisiológicas/diagnóstico , Disfunciones Sexuales Psicológicas/diagnóstico , Factores de TiempoRESUMEN
The present study is trying to produce a transdermal microemulsion drug delivery system (TMDDS) for Tripterygium Wilfordii Hook f. (TWHF) and attempting to solve male reproductive toxicity problem of TWHF. The formulation was optimized by the central composite design with response surface methodology and was decided as 12% oleic acid, 19.7% Labrasol S, 19.7% ethanol and 19.7% Pharmasolve, and 29% water. TMDDS for TWHF had stronger transdermal ability than free TWHF, and TWHF microemulsion significantly inhibited the adjuvant-induced arthritis and at the same time, had preferable anti-inflammatory effect with the long-time administration. Various pharmacodynamics parameters proved that TWHF microemulsion can reduce the male reproductive toxicity and hepatotoxicity of rats. All these suggested that TMDDS could be a suitable delivery system for TWHF.
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Antiinflamatorios/administración & dosificación , Artritis/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Sistemas de Liberación de Medicamentos , Enfermedades Urogenitales Masculinas/prevención & control , Extractos Vegetales/administración & dosificación , Tripterygium/toxicidad , Administración Cutánea , Animales , Antiinflamatorios/uso terapéutico , Antiinflamatorios/toxicidad , Artritis/inducido químicamente , Emulsiones , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Ratas , Agua/químicaRESUMEN
OBJECTIVE: This article provides a comprehensive review of the role of MDCT and MRI in the diagnosis of drug-induced complications in the abdomen and pelvis in adults. A systematic organ-based review of these complications is presented, including but not limited to hepatic changes after chemotherapy, renal complications such as tumor lysis syndrome and lithium nephropathy, gastrointestinal manifestations, various opportunistic infections and secondary neoplasms, mycotic aortic aneurysm from intravesical bacille Calmette-Guérin, complications of anticoagulant therapy, and oral contraceptives. CONCLUSION: Advancements in imaging have led to recognition of radiologic features of previously unsuspected diseases. Occasionally, imaging may also identify effects of treatments instituted for these diseases. Consequently, imaging plays a critical role in the accurate diagnosis of a broad spectrum of drug-induced complications in the abdomen, both in emergent and nonemergent settings. Knowledge of the natural history, clinical manifestations, and salient imaging features of these entities is crucial to facilitate accurate clinical diagnosis in a timely fashion.
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Enfermedades del Sistema Digestivo/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades Urogenitales Femeninas/inducido químicamente , Enfermedades Urogenitales Femeninas/diagnóstico , Imagen por Resonancia Magnética/métodos , Enfermedades Urogenitales Masculinas/inducido químicamente , Enfermedades Urogenitales Masculinas/diagnóstico , Tomografía Computarizada por Rayos X/métodos , Enfermedades Vasculares/inducido químicamente , Enfermedades Vasculares/diagnóstico , Medios de Contraste , Enfermedades del Sistema Digestivo/diagnóstico por imagen , Femenino , Enfermedades Urogenitales Femeninas/diagnóstico por imagen , Humanos , Masculino , Enfermedades Urogenitales Masculinas/diagnóstico por imagen , Enfermedades Vasculares/diagnóstico por imagenRESUMEN
INTRODUCTION: Radiotherapy and androgen deprivation are an established treatment option for locally advanced prostate cancer. We evaluate outcomes in efficacy and toxicity for patients treated with this combined therapy at our institution. METHODS: A retrospective study of 80 patients with locally advanced prostate cancer treated with radiotherapy combined with neo-adjuvant (2 months) and adjuvant (24 months) androgen deprivation. We studied the clinical variables and side effects. We evaluated treatment outcomes using PSA nadir and biochemical failure, and recorded acute and late gastrointestinal and urinary toxicity. We assessed the correlation between clinical variables and urinary toxicity by means of univariate and multivariate analyses (multiple logistic regression). RESULTS: The mean patient age was 68 ± 5.81 years; the initial PSA was 20.05 ± 16.27 ng/ ml and the mean prostate volume 43.7 ± 27.57 cc. The clinical stage was T3a in 33% and T3b in 66%. The Gleason score was <7 in 39%, 7 in 46% and ≥8 in 15%. The mean follow-up was 44.4 months and biochemical failure was observed in 3 cases. Acute urinary toxicity was recorded in 90% of the patients (chronic in 35%) and acute gastrointestinal toxicity in 75% (late in 32%). In a univariate analysis, prostate volume and urinary symptoms were statistically correlated to acute and late urinary toxicity. Both prostate volume and urinary symptoms were independently associated with an increase in urinary toxicity in the logistic regression analysis. CONCLUSIONS: Hormone-radiotherapy is a valid option to locally treat advanced prostate cancer with optimal short-term outcomes, although it is not devoid of side effects. Prostate volume and urinary symptoms before treatment can predict genitourinary toxicity.
Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Anciano , Antagonistas de Andrógenos/efectos adversos , Terapia Combinada , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Estadificación de Neoplasias , Neoplasias de la Próstata/patología , Estudios RetrospectivosRESUMEN
Cancer chemotherapy has evolved from cytotoxic agents and now includes several new agents that target specific molecules responsible for the regulation of cell growth, nutrient supply, and differentiation. These molecularly targeted therapies have a different mechanism of action than do classic cytotoxic agents, which predominantly attack rapidly proliferating cells. Not surprisingly, therefore, the toxicity of targeted and cytotoxic agents may differ in both clinical and radiologic presentation. Many of the toxicities of targeted therapies are not cumulative or dose dependent, some are asymptomatic, and others may first manifest radiologically. It is imperative that radiologists be aware of these toxicities and that they learn to recognize the relevant findings so that they can provide a complete differential diagnosis and thus play an important role in patient care.
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Antineoplásicos/efectos adversos , Terapia Molecular Dirigida/efectos adversos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Tomografía Computarizada por Rayos X , Femenino , Enfermedades Urogenitales Femeninas/inducido químicamente , Enfermedades Urogenitales Femeninas/diagnóstico por imagen , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/diagnóstico por imagen , Humanos , Hepatopatías/diagnóstico por imagen , Hepatopatías/etiología , Enfermedades Pulmonares/inducido químicamente , Enfermedades Pulmonares/diagnóstico por imagen , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Enfermedades Urogenitales Masculinas/diagnóstico por imagen , Enfermedades Pancreáticas/inducido químicamente , Enfermedades Pancreáticas/diagnóstico por imagen , Enfermedades Vasculares/inducido químicamente , Enfermedades Vasculares/diagnóstico por imagenRESUMEN
BACKGROUND: The upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor. OBJECTIVE: We investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero. METHODS: In this cohort study of sons born to women accidentally exposed to PBBs during 1973-1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth. RESULTS: Of 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [< or =1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8-5.1]. This risk was increased when we excluded sons born after the exposure but before the mother's serum PBB measurement (OR = 3.1; 95% CI, 1.0-9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure. CONCLUSIONS: Although cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.
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Retardadores de Llama/efectos adversos , Exposición Materna , Bifenilos Polibrominados/sangre , Sistema Urogenital/efectos de los fármacos , Adolescente , Adulto , Niño , Preescolar , Criptorquidismo/inducido químicamente , Criptorquidismo/epidemiología , Femenino , Hernia/inducido químicamente , Hernia/epidemiología , Humanos , Hipospadias/inducido químicamente , Hipospadias/epidemiología , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Enfermedades Urogenitales Masculinas/epidemiología , Bifenilos Polibrominados/antagonistas & inhibidores , Embarazo , Efectos Tardíos de la Exposición Prenatal , Hidrocele Testicular/inducido químicamente , Hidrocele Testicular/epidemiología , Sistema Urogenital/patología , Adulto JovenRESUMEN
INTRODUCTION: To date, little information exists regarding urogenital diseases in those who have been exposed to sulfur mustard (SM). We report the self-reported history of urologic conditions and findings on physical examination in a group of male veterans 19 to 26 years after exposed to high-dose sulfur mustard. MATERIALS AND METHODS: Data on urologic health conditions of a nationwide health survey were used in this study. This survey included all 289 Iranian male veterans who had been exposed to high doses of SM between 1983 and 1989. Demographic data, exposure-related data, health status, and also self-reported lifetime history of urologic conditions were analyzed. History of benign prostatic hyperplasia, recurrent urinary tract infections, pyelonephritis, urinary calculi, kidney failure, and urogenital neoplasms were specifically concerned. RESULTS: The mean age of the veterans was 45.0 ? 7.5 years (range, 30 to 75 years). An interval of 19 to 26 years had passed from exposure to SM. Fifty veterans (17.3%) had a positive history of urinary calculi, 25 (8.7%) had recurrent urinary tract infections, 5 (1.7%) had BPH, and 2 (0.7%) had kidney failure. None of them had experienced urogenital malignancies. Neither recurrent urinary tract infections nor urinary calculi were significantly associated with age, medications and their doses, or SM-induced late complications in other organs. CONCLUSION: This study adds the prevalence of self-reported urologic conditions to our limited knowledge on SM-exposed veterans' health condition, without finding any link neither to demographic, nor to the severity of health complications related to the SM exposure.
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Sustancias para la Guerra Química/efectos adversos , Exposición por Inhalación/efectos adversos , Enfermedades Urogenitales Masculinas/inducido químicamente , Enfermedades Urogenitales Masculinas/epidemiología , Anamnesis/estadística & datos numéricos , Gas Mostaza/efectos adversos , Veteranos/estadística & datos numéricos , Adulto , Distribución por Edad , Anciano , Distribución de Chi-Cuadrado , Enfermedad Crónica , Encuestas Epidemiológicas , Humanos , Incidencia , Masculino , Enfermedades Urogenitales Masculinas/fisiopatología , Persona de Mediana Edad , Probabilidad , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/epidemiología , Hiperplasia Prostática/fisiopatología , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/epidemiología , Insuficiencia Renal/fisiopatología , Medición de Riesgo , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Encuestas y Cuestionarios , Factores de Tiempo , Cálculos Urinarios/inducido químicamente , Cálculos Urinarios/epidemiología , Cálculos Urinarios/fisiopatología , Infecciones Urinarias/inducido químicamente , Infecciones Urinarias/epidemiología , Infecciones Urinarias/fisiopatologíaRESUMEN
PURPOSE: Zinc is a common dietary supplement that is widely believed to have beneficial health effects. To assess the impact of high dose supplemental zinc on genitourinary diseases we analyzed a recent randomized trial comparing zinc, antioxidants and their combination to placebo for complications related to the genitourinary tract. MATERIALS AND METHODS: In a further analysis of the recent Age-related Eye Disease Study we examined the data pool for primary International Classification of Diseases, 9th revision codes given for hospital admissions related to urological problems. The Age-Related Eye Disease Study randomized 3,640 patients with age related macular degeneration to 1 of 4 study arms, including placebo, antioxidants (500 mg vitamin C, 400 IU vitamin E and 15 mg beta-carotene), 80 mg zinc and antioxidant plus zinc. Statistical analyses using Fisher's exact test were performed. RESULTS: We found a significant increase in hospital admissions due to genitourinary causes in patients on zinc vs nonzinc formulations (11.1% vs 7.6%, p = 0.0003). The risk was greatest in male patients (RR 1.26, 95% CI 1.07-1.50, p = 0.008). In the study group of 343 patients requiring hospital admission the most common primary International Classification of Diseases, 9th revision codes included benign prostatic hyperplasia/urinary retention (benign prostatic hyperplasia), urinary tract infection, urinary lithiasis and renal failure. When comparing zinc to placebo, significant increases in urinary tract infections were found (p = 0.004), especially in females (2.3% vs 0.4%, RR 5.77, 95% CI 1.30-25.66, p = 0.013). Admissions for urinary lithiasis approached significance in men on zinc compared to placebo (2.0% vs 0.5%, RR = 4.08, 95% CI 0.87-19.10). There was no increase in prostate or other cancers with zinc supplementation. A significant decrease in prostate cancer diagnoses was seen in patients receiving antioxidants vs placebo (RR = 0.6, 95% CI 0.49-0.86, p = 0.049). Subgroup analysis revealed that this finding was significant in men who smoked but not in nonsmokers. CONCLUSIONS: Zinc supplementation at high levels results in increased hospitalizations for urinary complications compared to placebo. These data support the hypothesis that high dose zinc supplementation has a negative effect on select aspects of urinary physiology.
Asunto(s)
Enfermedades Urogenitales Femeninas/inducido químicamente , Enfermedades Urogenitales Femeninas/epidemiología , Enfermedades Urogenitales Masculinas/inducido químicamente , Enfermedades Urogenitales Masculinas/epidemiología , Admisión del Paciente/estadística & datos numéricos , Zinc/administración & dosificación , Zinc/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To assess the feasibility and tolerance of neoadjuvant and concomitant estramustine phosphate and vinblastine (EV) with high-dose three-dimensional conformal radiotherapy (3D-CRT) for patients with unfavorable-risk prostate cancer. PATIENTS AND METHODS: Twenty-seven patients with unfavorable-risk prostate cancer were enrolled onto a prospective study to determine the feasibility of combining EV with 3D-CRT. Patients were eligible if any of the following requirements were satisfied: (1) Gleason score > or =8 and prostate-specific antigen (PSA) > 10 ng/mL; (2) Gleason score of 7 and PSA > 20 ng/mL; (3) clinical stage T3N0M0 disease with PSA > 20 ng/mL; (4) any patient with T4N0M0 disease; or (5) patients with TXN1MO disease. Therapy consisted of three 8-week cycles of EV and 8 weeks of 3D-CRT. Estramustine phosphate was given orally beginning on week 1 and continued until the completion of 3D-CRT. Each 8-week cycle of vinblastine consisted of 6 weekly intravenous injections followed by a 2-week rest period. Radiation therapy was administered using a three-dimensional conformal approach to a prescription dose of 75.6 Gy. The median follow-up was 26 months (range, 6 to 40 months). RESULTS: Twenty-three (85%) of 27 patients completed the entire course of therapy and were assessable for toxicities and biochemical outcome. Two patients (7%) developed grade 3 hematologic toxicity that resolved, and two patients (7%) developed grade 3 hepatoxicity, manifesting as persistent elevation of serum transaminase levels, necessitating discontinuation of the chemotherapy and withdrawal from the treatment program. The most prominent adverse effects from this regimen were mild to moderate (grade 1 to 2) nausea and fatigue related to estramustine. Mild peripheral edema was seen in 15% of patients and was treated with diuresis. 3D-CRT was tolerated well in these patients. Medications were required for relief of acute grade 2 rectal (gastrointestinal [GI]) and urinary (genitourinary [GU]) symptoms in 35% and 48% of patients, respectively. Three patients developed acute grade 3 GU toxicities. The 2-year actuarial likelihood of late grade 2 GI toxicity was 20%. No late grade 3 or 4 GI toxicities were observed. The 2-year actuarial likelihoods of late grade 2 and 3 GU toxicities were 25% and 12%, respectively. No grade 4 GU toxicity was observed. CONCLUSION: Neoadjuvant and concomitant EV with high-dose 3D-CRT is well tolerated in patients with unfavorable-risk prostate cancer. Although the incidence of modest (grade 2) late GI and GU toxicities seem to be increased compared with 3D-CRT alone or in combination with androgen ablation therapy, no severe toxicities were encountered with this regimen.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Radioterapia Conformacional , Administración Oral , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Estramustina/administración & dosificación , Etopósido/administración & dosificación , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Inyecciones Intravenosas , Masculino , Enfermedades Urogenitales Masculinas/inducido químicamente , Terapia Neoadyuvante , Estudios Prospectivos , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/patología , Dosificación Radioterapéutica , Radioterapia Conformacional/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vindesina/administración & dosificaciónRESUMEN
A 56-year old man was hospitalized for spasmodic paraparesis with sphincter disorders. After exclusion of spinal cord compression and all other inflammatory, infectious or neoplastic causes, the possibility of a connexion with an hepatitis B vaccination performed with a recumbent vaccine three weeks before the neurological disorders appeared was considered. The pathogenesis of such a myelitis remains uncertain. It is based on the possible reactivation of a dormant virus or a crossed antigenic reaction between a protein of the vaccine and the nervous system. The course of the disease is usually favourable. The frequency of this complication would be more accurately determined if all neurological manifestations occurring after hepatitis B vaccination were reported.