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1.
Clin Endocrinol (Oxf) ; 89(4): 470-473, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29923212

RESUMO

OBJECTIVE: Case reports have suggested an increased risk of gynecomastia with HMG-CoA reductase inhibitors (ie, statins). A recent meta-analysis also found that statins decrease circulating testosterone levels in men. We investigated whether statin use was associated with an increased risk of gynecomastia. DESIGN: Case-control study. PATIENTS: A cohort of patients from a random sample of 9 053 240 US subjects from the PharMetrics Plus™ health claims database from 2006 to 2016 was created. MEASUREMENTS: New cases of gynecomastia requiring at least two ICD-9 codes were identified from the cohort and matched to 10 controls by follow-up time and age using density-based sampling. Rate ratios (RRs) for users of statins were computed using conditional logistic regression adjusting for alcoholic cirrhosis, hyperthyroidism, testicular cancer, Klinefelter syndrome, obesity, hypogonadism, hyperprolactinemia and use of spironolactone, ketoconazole, H2 receptor antagonists (H2 blockers), risperidone, testosterone and androgen deprivation therapy. RESULTS: Our cohort included 6147 cases of gynecomastia and 61 470 corresponding matched controls. The adjusted RR for current, recent and past statin use with respect to gynecomastia was 1.19 (1.04-1.36), 1.38 (1.15-1.65) and 1.20 (1.03-1.40), respectively. CONCLUSIONS: Statin use is associated with an increased risk of developing gynecomastia. Clinicians should be cognizant of this effect and educate patients accordingly.


Assuntos
Ginecomastia/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Adolescente , Adulto , Estudos de Casos e Controles , Ginecomastia/etiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
J Urol ; 197(5): 1309-1314, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27866006

RESUMO

PURPOSE: Randomized controlled trials suggest an increased risk of heart failure with dutasteride, which inhibits both the type 1 and type 2 isoforms of 5α-reductase. In contrast, no such association has been suggested for finasteride, which selectively inhibits the type 2 isoform. We investigated the risk of cardiovascular events among patients receiving dutasteride relative to finasteride. MATERIALS AND METHODS: We performed a population based cohort study of Ontario men 66 years old or older who commenced treatment with dutasteride or finasteride between October 1, 2005 and March 31, 2015. For each individual treated with dutasteride, we identified 1 treated with finasteride, matching on a propensity score and calendar quarter of treatment initiation to account for temporal changes in prescribing. The primary outcome was hospitalization for heart failure. Secondary analyses were done to examine acute myocardial infarction and stroke. Cox proportional hazards regression was used to adjust for differences between groups. RESULTS: We studied 36,311 men who commenced dutasteride and 36,311 treated with finasteride. In the primary analysis, we found no difference in the risk of heart failure among patients receiving dutasteride relative to those receiving finasteride (adjusted HR 0.98, 95% CI 0.88-1.08). Similarly, we found no difference in the risk of acute myocardial infarction (HR 0.94, 95% CI 0.82-1.08) or stroke (HR 1.03, 95% CI 0.88-1.20). CONCLUSIONS: In this population based cohort study of more than 72,000 older men, dutasteride was not associated with an increased risk of cardiovascular events relative to finasteride.


Assuntos
Inibidores de 5-alfa Redutase/efeitos adversos , Dutasterida/efeitos adversos , Finasterida/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Infarto do Miocárdio/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Idoso , Estudos de Coortes , Bases de Dados Factuais , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Infarto do Miocárdio/epidemiologia , Ontário , Hiperplasia Prostática/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia
3.
J Sex Med ; 14(12): 1597-1605, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29198514

RESUMO

BACKGROUND: Erectile dysfunction (ED) can be a sentinel marker for future cardiovascular disease and has been described as providing a "window of curability" for men to receive targeted cardiovascular risk assessment. AIM: To determine whether the prescription of phosphodiesterase type 5 inhibitors (PDE5is) for ED leads to the detection and treatment of previously undiagnosed cardiometabolic risk factors. METHODS: We performed a retrospective population-based cohort study of residents of British Columbia, Canada using linked health care databases from 2004 to 2011. An individual-level time series analysis with switching replications was used to determine changes in drug use for hypertension, hypercholesterolemia, and diabetes in men 40 to 59 years old. The observation window for each patient was 720 days before and 360 days after the index date. OUTCOMES: The primary outcome was changes in prescriptions for antihypertensive, statin, and oral antidiabetic drugs, with secondary outcomes being laboratory tests for plasma cholesterol and glucose. RESULTS: 5,858 men 40 to 59 years old newly prescribed a PDE5i were included in the analysis. We found a sudden increase in prescriptions for antihypertensive drugs (40 per 1,000; P < .001), statins (10 per 1,000; P = .001), and antidiabetic drugs (17 per 1,000; P = .002) in the 90 days after a new prescription for a PDE5i. For hypercholesterolemia and diabetes, most of this change was observed in men with relevant screening tests performed in the 30 days after their PDE5i prescription. Only 15% and 17% of men who did not have a screening test for cholesterol and glucose, respectively, in the year before their PDE5i prescription went on to have one in the subsequent 30 days. CLINICAL IMPLICATIONS: The paucity of screening tests observed in our study after PDE5i prescriptions suggests that physicians should be educated on the recommended screening guidelines for men newly diagnosed with ED. STRENGTHS AND LIMITATIONS: The number of men who were ordered a laboratory test or written a prescription but chose not to complete or fill it, respectively, is unknown. CONCLUSION: Treatment for ED with PDE5is can be a trigger or "gateway drug" for the early detection and treatment of cardiometabolic risk factors provided physicians perform the requisite screening investigations. Skeldon SC, Cheng L, Morgan SG, et al. Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study. J Sex Med 2017;14:1597-1605.


Assuntos
Anti-Hipertensivos/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Hipertensão/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Síndrome Metabólica/tratamento farmacológico , Inibidores da Fosfodiesterase 5/efeitos adversos , Adulto , Canadá/epidemiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
4.
J Gen Intern Med ; 30(4): 514-20, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25338730

RESUMO

BACKGROUND: Direct-to-consumer advertising (DTCA) remains a controversial issue, with concerns that it leads to unnecessary and inappropriate prescribing. Whether DTCA shifts prescribing from first-line (guideline-recommended) therapy to second-line drugs has not been studied. OBJECTIVE: The purpose of this study was to determine the impact of sequential DTCA campaigns for two drugs used to treat benign prostatic hyperplasia (BPH): one newer agent, dutasteride (Avodart(®)), and one older first-line agent, tamsulosin (Flomax(®)). DESIGN: Interrupted time series analysis was used to assess the impact of each DTCA campaign using data on consumer "response" from Google Trends and dispensed prescriptions from IMS Health. PARTICIPANTS: We analyzed data for the United States from January 2003 to December 2007. INTERVENTION: DTCA for dutasteride and tamsulosin commenced on July, 2005 and April, 2006, respectively. MAIN MEASURES: Monthly Internet search volume (scaled from 0 to 100) for the advertised trade name of each drug and monthly U.S. prescription rates per 1,000 population were analyzed. KEY RESULTS: The dutasteride campaign was associated with an increase in Internet searches for both "Avodart" (level change +31.3 %, 95 % CI: 27.2-35.4) and "Flomax" (level change +8.3 %, 95 % CI: 0.9-15.7), whereas the tamsulosin campaign was associated with increased "Flomax" searches (level change +25.3 %, 95 % CI: 18.7-31.8). The dutasteride campaign was associated with an increase in the prescription of dutasteride (trend = 0.45/month, 95 % CI: 0.33-0.56), but a larger impact was observed with tamsulosin prescriptions (trend = 0.76/month, 95 % CI: 0.02-1.50). Similarly, the tamsulosin campaign was associated with an immediate fourfold increase in the prescribing of tamsulosin (level change +5.76 units, 95 % CI: 1.79-9.72) compared to dutasteride (level change +1.47 units, 95 % CI: 0.79-2.14). CONCLUSIONS: DTCA was associated with the utilization of drugs to treat symptomatic BPH. However, both campaigns were associated with greater increases in the use of the guideline-recommended first-line agent. DTCA campaigns may increase the overall levels of guideline-recommended treatments to a greater extent than the specific advertised agents.


Assuntos
Publicidade Direta ao Consumidor/métodos , Análise de Séries Temporais Interrompida/métodos , Hiperplasia Prostática/tratamento farmacológico , Publicidade Direta ao Consumidor/tendências , Dutasterida/uso terapêutico , Humanos , Prescrição Inadequada/prevenção & controle , Prescrição Inadequada/tendências , Análise de Séries Temporais Interrompida/tendências , Masculino , Hiperplasia Prostática/epidemiologia , Sulfonamidas/uso terapêutico , Tansulosina , Estados Unidos , Agentes Urológicos/uso terapêutico
5.
Ann Fam Med ; 13(4): 331-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26195677

RESUMO

PURPOSE: We investigated whether erectile dysfunction, a marker for future cardiovascular disease, is associated with undiagnosed cardiometabolic risk factors among US men. Identifying the presence of these risk factors could lead to earlier initiation of treatment for primary prevention of cardiovascular disease. METHODS: We analyzed cross-sectional data from men aged 20 years and older who participated in the National Health and Nutrition Examination Survey during 2001-2004. Erectile dysfunction was determined by a single, validated survey question. We used logistic regression analyses to investigate the relationship between erectile dysfunction and undiagnosed hypertension, hypercholesterolemia, and diabetes. RESULTS: After multivariate adjustment, men with erectile dysfunction had more than double the odds of having undiagnosed diabetes (odds ratio = 2.20; 95% CI, 1.10-4.37), whereas no association was seen for undiagnosed hypertension or undiagnosed hypercholesterolemia. For the average man aged 40 to 59 years, the predicted probability of having undiagnosed diabetes increased from 1 in 50 in the absence of erectile dysfunction to 1 in 10 in the presence of erectile dysfunction. CONCLUSIONS: Our results underscore the importance of erectile dysfunction as a marker of undiagnosed diabetes. Erectile dysfunction should be a trigger to initiate diabetes screening, particularly among middle-aged men.


Assuntos
Complicações do Diabetes , Diabetes Mellitus/diagnóstico , Disfunção Erétil/complicações , Hipercolesterolemia/diagnóstico , Hipertensão/diagnóstico , Adulto , Fatores Etários , Estudos Transversais , Humanos , Hipercolesterolemia/complicações , Hipertensão/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Fatores de Risco , Estados Unidos , Adulto Jovem
6.
Can Urol Assoc J ; 11(12): 396-403, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29106358

RESUMO

INTRODUCTION: In 2014, the Canadian Task Force on Preventive Health Care (CTFPHC) recommended against routine prostate cancer screening with the prostate-specific antigen (PSA) blood test. We surveyed Canadian primary care physicians (PCPs) to understand their opinions and attitudes towards prostate cancer screening in 2016. METHODS: Twenty PCPs piloted the survey to assess its accessibility. We distributed a flyer to 19 633 PCPs as an insert in a large mailed package inviting them to attend a national meeting, and later promoted the survey at the meeting. Multinomial logistic regression models examined factors associated with agreement of key guideline statements and the overall benefit of PSA screening. RESULTS: A total of 1254 PCPs responded (rate of 6.4%); 54.7% of physicians aware of the CTFPHC recommendations report screening less often as a result. Overall, 55.6% of PCPs feel that the risks of PSA screening outweigh the benefits. On multivariable analysis, physicians who did not read the guidelines, did not have an academic appointment, or were in practice for over 20 years were significantly more likely to disagree with the statement that men 55-69 years old should not be screened for prostate cancer with PSA. CONCLUSIONS: Our national survey found that the prostate cancer screening practices of Canadian PCPs varies widely across physician demographic groups, with almost equal numbers for or against. This has significant ethical, medical, and legal implications. The poor response rate to highly incentivized survey request may suggest a reluctance or general apathy towards this subject because of the Task Force recommendations. Future efforts should provide physicians with objective guidance around PSA screening, incorporating input from all stakeholders, including PCPs, urologists, and patients.

7.
Urol Oncol ; 33(1): 40-44, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24745663

RESUMO

Bladder cancer is the fourth most common cancer among men in the United States, with a 3-fold higher incidence than women. Globally, tobacco smoking remains significantly more common in men, contributing to half of all cases of bladder cancer. To prevent bladder cancer, urologists should promote smoking cessation to patients presenting at earlier ages with concerns such as sexual dysfunction, infertility, pelvic pain, or vasectomy. Bladder cancer also provides an entry point for men into the healthcare system, at which time, urologists can discuss and coordinate attention to other male health issues such as cardiovascular illness, depression, or addiction. By assuming the role of men's health physicians, urologists can have a significant benefit on men's urologic and overall health by targeting risk factors and behaviors.


Assuntos
Neoplasias da Bexiga Urinária/terapia , Feminino , Humanos , Masculino , Saúde do Homem/tendências , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/prevenção & controle
8.
Pharmacotherapy ; 35(1): 72-8, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25582846

RESUMO

BACKGROUND: Recent studies have provided conflicting and controversial results about the risk of cardiovascular events, including myocardial infarction (MI), with testosterone replacement therapy (TRT). The potential adverse effects of different TRT formulations and duration of therapy on MI risk are unknown. METHODS: We performed a case-control study within a cohort of 934,283 men aged 45-80 from the IMS LifeLink Health Plan Claims Database. For each case of MI, four controls were identified using density-based sampling. Rate ratios (RRs) were computed for current and past TRT users. As a sensitivity analysis, the risk of MI before and after the start of a first-time TRT prescription in the same patient was also computed. RESULTS: We identified 30,066 MI cases and 120,264 corresponding controls. Current use of TRT was not associated with an increased risk of MI (RR 1.01, 95% confidence interval [CI] 0.89-1.16); first-time users did show an increased risk (RR 1.41, 95% CI 1.06-1.87; number needed to harm 305). There was no association between MI and past TRT users and no differences among the different formulations. The RRs for current use and first-time use of TRT in men with a previous history of coronary artery disease were 1.05 (95% CI 0.79-1.41) and 1.78 (95% CI 0.93-3.40), respectively. CONCLUSION: In this large observational study, an association between MI and past or current TRT use was not found. However, a statistically significant association was observed between first-time TRT exposure and MI, although the absolute risk was low.


Assuntos
Terapia de Reposição Hormonal , Infarto do Miocárdio/epidemiologia , Farmacoepidemiologia , Testosterona/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica/epidemiologia , Estudos de Casos e Controles , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , Terapia de Reposição Hormonal/efeitos adversos , Terapia de Reposição Hormonal/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Estudos Retrospectivos , Risco , Testosterona/administração & dosagem
9.
Nat Rev Urol ; 11(3): 169-77, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24535583

RESUMO

Illicit drug use is prevalent worldwide; over 24 million people are estimated to have used recreational drugs during the past month in the UK and USA alone. Illicit drug use can result in a wide spectrum of potential medical complications that include many urological manifestations. To ensure optimal care and treatment, urologists need to be cognizant of these complications in their patients, particularly among youths. Ketamine uropathy is thought to affect over one-quarter of ketamine users and can lead to severe lower urinary tract symptoms, as well as upper tract obstruction. Cannabis use has been associated with an increased risk of bladder cancer, prostate cancer and nonseminomatous germ cell tumours in case-control studies. Fournier's gangrene has been reported following injection of heroin and cocaine into the penis. Excessive use of cough medicines can lead to the development of radiolucent stones composed of ephedrine, pseudoephedrine and guaifenesin. As the current evidence is mostly limited to case reports and case series, future epidemiological studies are needed to fully address this issue.


Assuntos
Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/complicações , Doenças Urológicas/induzido quimicamente , Gangrena de Fournier/induzido quimicamente , Gangrena de Fournier/diagnóstico , Gangrena de Fournier/terapia , Humanos , Sintomas do Trato Urinário Inferior/induzido quimicamente , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/terapia , Masculino , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/terapia , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/terapia , Doenças Urológicas/diagnóstico , Doenças Urológicas/terapia
10.
Urology ; 83(5): 1099-103, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24767524

RESUMO

OBJECTIVE: To determine patients' knowledge regarding their nerve-sparing status (NSS) after radical prostatectomy (RP) and what factors during their clinical treatment are associated with this. METHODS: One hundred consecutive patients attending an erectile dysfunction clinic in Toronto, Canada, with a prior RP were surveyed from December 2010 to June 2011. Patients were questioned whether they had undergone a nerve-sparing procedure and, if so, whether it was unilateral or bilateral. Patients were assessed on both knowledge (known vs unknown) and accuracy (correct vs incorrect) regarding their NSS. Operative reports were used to determine the true NSS of each patient. RESULTS: Thirty-nine percent of patients had no knowledge of their NSS. Forty-five percent of patients were able to correctly identify their NSS, including only 19% of patients undergoing a non-nerve-sparing procedure. On univariate analysis, factors associated with patients correctly knowing their NSS were age, having a nerve-sparing strategy dictated in the preoperative clinic note, nerve sparing included in the surgical consent form, and type of nerve-sparing procedure performed. On multivariate analysis, planned nerve-sparing approach dictated in the preoperative note (odds ratio [OR], 4.86), nerve sparing included in surgical consent (OR, 3.76), time since surgery (OR, 0.99), and having a bilateral nerve-sparing procedure (OR, 5.91) were associated with correctly identifying one's NSS. CONCLUSION: After RP, a significant proportion of patients with erectile dysfunction have no knowledge of whether they underwent a nerve-sparing procedure. By discussing with patients the planned nerve-sparing technique preoperatively and counseling them on their NSS postoperatively, urologists may be able to improve on patient recollection of their NSS.


Assuntos
Tratamentos com Preservação do Órgão , Prostatectomia/métodos , Idoso , Disfunção Erétil , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Estudos Retrospectivos
11.
Urology ; 83(4): 888-92, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24680458

RESUMO

OBJECTIVE: To investigate whether the amount of striated muscle (SM) removed with the apical aspect of the prostate at prostatectomy can be predictive of postprostatectomy urinary incontinence (UI). METHODS: The records of 61 consecutive patients seen in follow-up after prostatectomy were reviewed. Complete clinical data were collected. Two uropathologists reviewed the hematoxylin and eosin sections of the apical margin to semiquantitatively assess the amount of SM according to the following scheme: 0 = no SM, 1 = 1%-10% SM (of total tissue), 2 = 11%-30% SM, and 3 = >30% SM. Continence status was determined based on the last clinical visit, with UI considered as any reported leakage. RESULTS: Patients had a median age of 62 years at surgery (interquartile range, 58-66 years) and had a median follow-up after surgery of 100 weeks (interquartile range, 50-176 weeks). Both prostate weight and SM score (P = .045 for both) were statistically significant predictors of incontinence on multivariate analysis. The odds of a patient with an average SM score of ≥2 being incontinent was 11.7 times that of a patient with an average score of <2. Using an SM score of ≥2 had a specificity of 98% and a sensitivity of 19% for detecting incontinence in patients after radical prostatectomy. CONCLUSION: The amount of SM seen in the pathology specimen after radical prostatectomy has a significant effect on postoperative UI.


Assuntos
Músculo Estriado/patologia , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Idoso , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Complicações Pós-Operatórias , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Incontinência Urinária/etiologia , Incontinência Urinária/prevenção & controle
12.
Urology ; 83(5): 992-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24674117

RESUMO

OBJECTIVE: To determine if lean methodology, an industrial engineering tool developed to optimize manufacturing efficiency, can successfully be applied to improve efficiencies and quality of care in a hospital-based high-volume uro-oncology clinic. METHODS: Before the lean initiative, baseline data were collected on patient volumes, wait times, cycle times (patient arrival to discharge), nursing assessment time, patient teaching, and physician ergonomics (via spaghetti diagram). Value stream analysis and a rapid improvement event were carried out, and significant changes were made to patient check-in, work areas, and nursing face time. Follow-up data were obtained at 30, 60, and 90 days. The Student t test was used for analysis to compare performance metrics with baseline. RESULTS: The median cycle time before the lean initiative was 46 minutes. This remained stable at 46 minutes at 30 days but improved to 35 minutes at 60 days and 41 minutes at 90 days. Shorter wait times allowed for increased nursing and physician face time. The average length of the physician assessment increased from 7.5 minutes at baseline to 10.6 minutes at 90 days. The average proportion of value-added time compared with the entire clinic visit increased from 30.6% at baseline to 66.3% at 90 days. CONCLUSION: Using lean methodology, we were able to shorten the patient cycle time and the time to initial assessment as well as integrate both an initial registered nurse assessment and registered nurse teaching to each visit. Lean methodology can effectively be applied to improve efficiency and patient care in an academic outpatient uro-oncology clinic setting.


Assuntos
Instituições de Assistência Ambulatorial/organização & administração , Instituições de Assistência Ambulatorial/normas , Eficiência Organizacional , Serviço Hospitalar de Engenharia e Manutenção/métodos , Oncologia , Qualidade da Assistência à Saúde , Urologia , Humanos , Fatores de Tempo
13.
BMJ ; 347: f6320, 2013 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-24192967

RESUMO

OBJECTIVE: To characterize risk of hypotension requiring admission to hospital in middle aged and older men treated with tamsulosin for benign prostatic hyperplasia. DESIGN: Population based retrospective cohort study (between patient methodology) and self controlled case series (within patient methodology). SETTING: Healthcare claims data from the IMS Lifelink database in the United States. PARTICIPANTS: Men aged 40-85 years with private US healthcare insurance entering the cohort at their first dispensing for tamsulosin or for a 5α reductase inhibitor (5ARI) between January 2001 and June 2011 after a minimum of six months' enrolment. MAIN OUTCOMES MEASURES: Hypotension requiring admission to hospital. Cox proportional hazards models estimated rate ratios at time varying intervals during follow-up: weeks 1-4, 5-8, and 9-12 after tamsulosin initiation; weeks 1-4, 5-8, and 9-12 after restarting tamsulosin (after a four week gap); and maintenance tamsulosin treatment (remaining exposed person time). Covariates included age, calendar year, demographics, antihypertensive use, healthcare use, and a Charlson comorbidity score. A self controlled case series, having implicit control for time invariant covariates, was additionally conducted. RESULTS: Among 383,567 new users of study drugs (tamsulosin 297,596; 5ARI 85,971), 2562 admissions to hospital for severe hypotension were identified. The incidence for hypotension was higher for tamsulosin (42.4 events per 10,000 person years) than for 5ARIs (31.3 events per 10,000 person years) or all accrued person time (29.1 events per 10,000 person years). After tamsulosin initiation, the cohort analysis identified an increased rate of hypotension during weeks 1-4 (rate ratio 2.12 (95% confidence interval 1.29 to 3.04)) and 5-8 (1.51 (1.04 to 2.18)), and no significant increase at weeks 9-12. The rate ratio for hypotension also increased at weeks 1-4 (1.84 (1.46 to 2.33)) and 5-8 (1.85 (1.45 to 2.36)) after restarting tamsulosin, as did maintenance tamsulosin treatment (1.19 (1.07 to 1.32)). The self controlled case series gave similar results as the cohort analysis. CONCLUSIONS: We observed a temporal association between tamsulosin use for benign prostatic hyperplasia and severe hypotension during the first eight weeks after initiating treatment and the first eight weeks after restarting treatment. This association suggests that physicians should focus on improving counseling strategies to warn patients regarding the "first dose phenomenon" with tamsulosin.


Assuntos
Inibidores de 5-alfa Redutase/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Hospitalização/estatística & dados numéricos , Hipotensão/epidemiologia , Hiperplasia Prostática/tratamento farmacológico , Inibidores de 5-alfa Redutase/efeitos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Seguimentos , Humanos , Hipotensão/induzido quimicamente , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Tansulosina , Estados Unidos
14.
Eur Urol ; 63(2): 379-85, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22883484

RESUMO

BACKGROUND: Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse. OBJECTIVE: To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations. DESIGN, SETTING, AND PARTICIPANTS: Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors. RESULTS AND LIMITATIONS: Eleven of 177 patients with MSH2 mutations (6.21%, p<0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias. CONCLUSIONS: LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinoma de Células de Transição/genética , Reparo de Erro de Pareamento de DNA/genética , Neoplasias Renais/genética , Síndrome de Lynch II/genética , Proteína 2 Homóloga a MutS/genética , Proteínas Nucleares/genética , Neoplasias Ureterais/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/epidemiologia , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Renais/epidemiologia , Pelve Renal , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Ontário/epidemiologia , Sistema de Registros , Fatores de Risco , Neoplasias Ureterais/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia
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