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1.
Eur Urol ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31537406

RESUMO

BACKGROUND: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. OBJECTIVE: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. DESIGN, SETTING, AND PARTICIPANTS: Men aged 40-69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. RESULTS AND LIMITATIONS: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

2.
Eur Urol ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31495749

RESUMO

BACKGROUND: BRCA1 and BRCA2 mutations have been associated with prostate cancer (PCa) risk but a wide range of risk estimates have been reported that are based on retrospective studies. OBJECTIVE: To estimate relative and absolute PCa risks associated with BRCA1/2 mutations and to assess risk modification by age, family history, and mutation location. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study of male BRCA1 (n = 376) and BRCA2 carriers (n = 447) identified in clinical genetics centres in the UK and Ireland (median follow-up 5.9 and 5.3 yr, respectively). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Standardised incidence/mortality ratios (SIRs/SMRs) relative to population incidences or mortality rates, absolute risks, and hazard ratios (HRs) were estimated using cohort and survival analysis methods. RESULTS AND LIMITATIONS: Sixteen BRCA1 and 26 BRCA2 carriers were diagnosed with PCa during follow-up. BRCA2 carriers had an SIR of 4.45 (95% confidence interval [CI] 2.99-6.61) and absolute PCa risk of 27% (95% CI 17-41%) and 60% (95% CI 43-78%) by ages 75 and 85 yr, respectively. For BRCA1 carriers, the overall SIR was 2.35 (95% CI 1.43-3.88); the corresponding SIR at age <65 yr was 3.57 (95% CI 1.68-7.58). However, the BRCA1 SIR varied between 0.74 and 2.83 in sensitivity analyses to assess potential screening effects. PCa risk for BRCA2 carriers increased with family history (HR per affected relative 1.68, 95% CI 0.99-2.85). BRCA2 mutations in the region bounded by positions c.2831 and c.6401 were associated with an SIR of 2.46 (95% CI 1.07-5.64) compared to population incidences, corresponding to lower PCa risk (HR 0.37, 95% CI 0.14-0.96) than for mutations outside the region. BRCA2 carriers had a stronger association with Gleason score ≥7 (SIR 5.07, 95% CI 3.20-8.02) than Gleason score ≤6 PCa (SIR 3.03, 95% CI 1.24-7.44), and a higher risk of death from PCa (SMR 3.85, 95% CI 1.44-10.3). Limitations include potential screening effects for these known mutation carriers; however, the BRCA2 results were robust to multiple sensitivity analyses. CONCLUSIONS: The results substantiate PCa risk patterns indicated by retrospective analyses for BRCA2 carriers, including further evidence of association with aggressive PCa, and give some support for a weaker association in BRCA1 carriers. PATIENT SUMMARY: In this study we followed unaffected men known to carry mutations in the BRCA1 and BRCA2 genes to investigate whether they are at higher risk of developing prostate cancer compared to the general population. We found that carriers of BRCA2 mutations have a high risk of developing prostate cancer, particularly more aggressive prostate cancer, and that this risk varies by family history of prostate cancer and the location of the mutation within the gene.

3.
Eur Urol ; 75(5): 834-845, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30527799

RESUMO

BACKGROUND: The homeobox B13 (HOXB13) G84E mutation has been recommended for use in genetic counselling for prostate cancer (PCa), but the magnitude of PCa risk conferred by this mutation is uncertain. OBJECTIVE: To obtain precise risk estimates for mutation carriers and information on how these vary by family history and other factors. DESIGN, SETTING, AND PARTICIPANTS: Two-fold: a systematic review and meta-analysis of published risk estimates, and a kin-cohort study comprising pedigree data on 11983 PCa patients enrolled during 1993-2014 from 189 UK hospitals and who had been genotyped for HOXB13 G84E. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relative and absolute PCa risks. Complex segregation analysis with ascertainment adjustment to derive age-specific risks applicable to the population, and to investigate how these vary by family history and birth cohort. RESULTS AND LIMITATIONS: A meta-analysis of case-control studies revealed significant heterogeneity between reported relative risks (RRs; range: 0.95-33.0, p<0.001) and differences by case selection (p=0.007). Based on case-control studies unselected for PCa family history, the pooled RR estimate was 3.43 (95% confidence interval [CI] 2.78-4.23). In the kin-cohort study, PCa risk for mutation carriers varied by family history (p<0.001). There was a suggestion that RRs decrease with age, but this was not significant (p=0.068). We found higher RR estimates for men from more recent birth cohorts (p=0.004): 3.09 (95% CI 2.03-4.71) for men born in 1929 or earlier and 5.96 (95% CI 4.01-8.88) for men born in 1930 or later. The absolute PCa risk by age 85 for a male HOXB13 G84E carrier varied from 60% for those with no PCa family history to 98% for those with two relatives diagnosed at young ages, compared with an average risk of 15% for noncarriers. Limitations include the reliance on self-reported cancer family history. CONCLUSIONS: PCa risks for HOXB13 G84E mutation carriers are heterogeneous. Counselling should not be based on average risk estimates but on age-specific absolute risk estimates tailored to individual mutation carriers' family history and birth cohort. PATIENT SUMMARY: Men who carry a hereditary mutation in the homeobox B13 (HOXB13) gene have a higher than average risk for developing prostate cancer. In our study, we examined a large number of families of men with prostate cancer recruited across UK hospitals, to assess what other factors may contribute to this risk and to assess whether we could create a precise model to help in predicting a man's prostate cancer risk. We found that the risk of developing prostate cancer in men who carry this genetic mutation is also affected by a family history of prostate cancer and their year of birth. This information can be used to assess more personalised prostate cancer risks to men who carry HOXB13 mutations and hence better counsel them on more personalised risk management options, such as tailoring prostate cancer screening frequency.

4.
BJU Int ; 2018 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-29802810

RESUMO

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening.

5.
Nat Genet ; 50(5): 682-692, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29662167

RESUMO

Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials.

7.
Br J Cancer ; 118(2): 266-276, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29301143

RESUMO

BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

8.
MMWR Morb Mortal Wkly Rep ; 67(1): 29-32, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29329280

RESUMO

In 2016, an estimated 1.5 million females aged 15-24 years were living with human immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the prevalence of HIV infection among adolescent girls and young women (3.4%) is more than double that for males in the same age range (1.6%) (1). Progress was assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020 targets for adolescent girls and young women in sub-Saharan Africa (90% of those with HIV infection aware of their status, 90% of HIV-infected persons aware of their status on antiretroviral treatment [ART], and 90% of those on treatment virally suppressed [HIV viral load <1,000 HIV RNA copies/mL]) (2) using data from recent Population-based HIV Impact Assessment (PHIA) surveys in seven countries. The national prevalence of HIV infection in adolescent girls and young women aged 15-24 years, the percentage who were aware of their status, and among those persons who were aware, the percentage who had achieved viral suppression were calculated. The target for viral suppression among all persons with HIV infection is 73% (the product of 90% x 90% x 90%). Among all seven countries, the prevalence of HIV infection among adolescent girls and young women was 3.6%; among those in this group, 46.3% reported being aware of their HIV-positive status, and 45.0% were virally suppressed. Sustained efforts by national HIV and public health programs to diagnose HIV infection in adolescent girls and young women as early as possible to ensure rapid initiation of ART should help achieve epidemic control among adolescent girls and young women.


Assuntos
Epidemias/prevenção & controle , Infecções por HIV/prevenção & controle , Adolescente , África/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Prevalência , Avaliação de Programas e Projetos de Saúde , Carga Viral/estatística & dados numéricos , Adulto Jovem
9.
Emerg Infect Dis ; 23(3): 396-404, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28220749

RESUMO

We describe the epidemiology of invasive Haemophilus influenzae disease during 2007-2014 in 12 European countries and assess overall H. influenzae disease trends by serotype and patient age. Mean annual notification rate was 0.6 cases/100,000 population, with an increasing annual trend of 3.3% (95% CI 2.3% to 4.3%). The notification rate was highest for patients <1 month of age (23.4 cases/100,000 population). Nontypeable H. influenzae (NTHi) caused 78% of all cases and showed increasing trends among persons <1 month and >20 years of age. Serotype f cases showed an increasing trend among persons >60 years of age. Serotype b cases showed decreasing trends among persons 1-5 months, 1-4 years, and >40 years of age. Sustained success of routine H. influenzae serotype b vaccination is evident. Surveillance systems must adopt a broad focus for invasive H. influenzae disease. Increasing reports of NTHi, particularly among neonates, highlight the potential benefit of a vaccine against NTHi.


Assuntos
Infecções por Haemophilus/epidemiologia , Infecções por Haemophilus/microbiologia , Haemophilus influenzae/isolamento & purificação , Adolescente , Adulto , Criança , Pré-Escolar , Europa (Continente)/epidemiologia , Haemophilus influenzae/classificação , Humanos , Lactente , Pessoa de Meia-Idade , Estudos Retrospectivos , Sorogrupo , Adulto Jovem
10.
Fam Cancer ; 16(3): 433-440, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28091804

RESUMO

In the United Kingdom, current screening guidelines for TP53 germline mutation carriers solely recommends annual breast MRI, despite the wide spectrum of malignancies typically seen in this group. This study sought to investigate the role of one-off non-contrast whole-body MRI (WB MRI) in the screening of asymptomatic TP53 mutation carriers. 44 TP53 mutation carriers and 44 population controls were recruited. Scans were read by radiologists blinded to participant carrier status. The incidence of malignancies diagnosed in TP53 mutation carriers against general population controls was calculated. The incidences of non-malignant relevant disease and irrelevant disease were measured, as well as the number of investigations required to determine relevance of findings. In TP53 mutation carriers, 6 of 44 (13.6, 95% CI 5.2-27.4%) participants were diagnosed with cancer during the study, all of which would be considered life threatening if untreated. Two were found to have two primary cancers. Two participants with cancer had abnormalities on the MRI which were initially thought to be benign (a pericardial cyst and a uterine fibroid) but transpired to be sarcomas. No controls were diagnosed with cancer. Fifteen carriers (34.1, 95% CI 20.5-49.9%) and seven controls (15.9, 95% CI 6.7-30.1%) underwent further investigations following the WB MRI for abnormalities that transpired to be benign (p = 0.049). The cancer detection rate in this group justifies a minimum baseline non-contrast WB MRI in germline TP53 mutation carriers. This should be adopted into national guidelines for management of adult TP53 mutation carriers in addition to the current practice of contrast enhanced breast MRI imaging.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Adulto , Feminino , Predisposição Genética para Doença/genética , Heterozigoto , Humanos , Incidência , Imagem por Ressonância Magnética , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Mutação , Neoplasias/epidemiologia , Reino Unido , Imagem Corporal Total/métodos , Adulto Jovem
11.
JAMA Oncol ; 2(11): 1434-1440, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27367496

RESUMO

Importance: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. Objective: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. Design, Setting, and Participants: This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. Main Outcomes and Measures: Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. Results: Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. Conclusions and Relevance: Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.


Assuntos
Genes BRCA1 , Genes BRCA2 , Salpingectomia , Neoplasias Uterinas/genética , Neoplasias Uterinas/prevenção & controle , Adulto , Feminino , Seguimentos , Humanos , Histerectomia , Perda de Heterozigosidade , Pessoa de Meia-Idade , Mutação , Ovariectomia , Estudos Prospectivos , Risco , Neoplasias Uterinas/epidemiologia
12.
Oncologist ; 21(6): 716-22, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27151655

RESUMO

BACKGROUND: A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. PATIENTS AND METHODS: A total of 100 men aged 40-69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. RESULTS: Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). CONCLUSION: The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress. IMPLICATIONS FOR PRACTICE: Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.


Assuntos
Biópsia , Detecção Precoce de Câncer , Polimorfismo de Nucleotídeo Único , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Adulto , Idoso , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Estudos de Viabilidade , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico por imagem
13.
J Am Podiatr Med Assoc ; 105(3): 264-72, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26146975

RESUMO

Unsafe practices are an underestimated contributor to the disease burden of bloodborne viruses. Outbreaks associated with failures in basic infection prevention have been identified in nonhospital settings with increased frequency in the United States during the past 15 years, representing an alarming trend and indicating that the challenge of providing consistently safe care is not always met. As has been the case with most medical specialties, public health investigations by state and local health departments, and the Centers for Disease Control and Prevention, have identified some instances of unsafe practices that have placed podiatric medical patients at risk for viral, bacterial, and fungal infections. All health-care providers, including podiatric physicians, must make infection prevention a priority in any setting in which care is delivered.


Assuntos
Controle de Infecções/organização & administração , Podiatria/métodos , Saúde Pública , Infecção da Ferida Cirúrgica/prevenção & controle , Humanos , Estados Unidos
14.
Emerg Infect Dis ; 21(8): 1317-21, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26196293

RESUMO

Health care services are increasingly delivered in outpatient settings. However, infection control oversight in outpatient settings to ensure patient safety has not improved and literature quantifying reported health care-associated infection outbreaks in outpatient settings is scarce. The objective of this analysis was to characterize investigations of suspected and confirmed outbreaks in outpatient settings in Los Angeles County, California, USA, reported during 2000-2012, by using internal logs; publications; records; and correspondence of outbreak investigations by characteristics of the setting, number, and type of infection control breaches found during investigations, outcomes of cases, and public health responses. Twenty-eight investigations met the inclusion criteria. Investigations occurred frequently, in diverse settings, and required substantial public health resources. Most outpatient settings investigated had >1 infection control breach. Lapses in infection control were suspected to be the outbreak source for 16 of the reviewed investigations.


Assuntos
Instituições de Assistência Ambulatorial/estatística & dados numéricos , Serviços de Saúde Comunitária/estatística & dados numéricos , Infecção Hospitalar/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Transmissão de Doença Infecciosa do Paciente para o Profissional/estatística & dados numéricos , Humanos , Controle de Infecções/estatística & dados numéricos , Los Angeles/epidemiologia
16.
Psychooncology ; 24(11): 1492-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25872100

RESUMO

BACKGROUND: The ability to identify men at genetically high-risk of prostate cancer (PrCa) would enable screening to be targeted at those most in need. This study explored the psychological impact (in terms of general and PrCa-specific worry and risk perceptions) on men with a family history of PrCa, undergoing prostate screening and genetic-risk profiling, within a research study. METHODS: A prospective exploratory approach was adopted, incorporating a sequential mixed-method design. Questionnaires were completed at two time points to measure the impact of undergoing screening and genetic-risk profiling. In-depth interviews were completed in a subgroup after all study procedures were completed and analysed using a framework approach. RESULTS: Ninety-five men completed both questionnaires, and 26 were interviewed. No measurable psychological distress was detectable in the group as a whole. The interview findings fell into two categories: 'feeling at risk' and 'living with risk'. The feeling of being at risk of PrCa is a part of men's lives, shaped by assumptions and information gathered over many years. Men used this information to communicate about PrCa risk to their peers. Men overestimate their risk of PrCa and have an innate assumption that they will develop PrCa. The interviews revealed that men experienced acute anxiety when waiting for screening results. CONCLUSIONS: Personalised genetic-risk assessments do not prevent men from overestimating their risk of PrCa. Screening anxiety is common, and timeframes for receiving results should be kept to a minimum. Methods of risk communication in men at risk of PrCa should be the subject of future research.


Assuntos
Detecção Precoce de Câncer/psicologia , Predisposição Genética para Doença/psicologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/psicologia , Adulto , Idoso , Ansiedade/psicologia , Seguimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pesquisa Qualitativa , Medição de Risco , Inquéritos e Questionários
17.
Urol Oncol ; 33(5): 202.e19-28, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25746941

RESUMO

OBJECTIVE: To evaluate the additive value of the prostate cancer gene 3 (PCA3) urine test to serum prostate-specific antigen (PSA) in prostate cancer (PC) screening among breast cancer, early-onset gene (BRCA) mutation carriers. This study was performed among the Dutch participants of IMPACT, a large international study on the effectiveness of PSA screening among BRCA mutation carriers. MATERIALS AND METHODS: Urinary PCA3 was measured in 191 BRCA1 mutation carriers, 75 BRCA2 mutation carriers, and 308 noncarriers. The physicians and participants were blinded for the results. Serum PSA level ≥ 3.0 ng/ml was used to indicate prostate biopsies. PCA3 was evaluated (1) as an independent indicator for prostate b iopsies and (2) as an indicator for prostate biopsies among men with an elevated PSA level. PC detected up to the 2-year screening was used as gold standard as end-of-study biopsies were not performed. RESULTS: Overall, 23 PCs were diagnosed, 20 of which were in men who had an elevated PSA level in the initial screening round. (1) PCA3, successfully determined in 552 participants, was elevated in 188 (cutoff ≥ 25; 34%) or 134 (cutoff ≥ 35; 24%) participants, including 2 of the 3 PCs missed by PSA. PCA3 would have added 157 (≥ 25; 28%) or 109 (≥ 35; 20%) biopsy sessions to screening with PSA only. (2) Elevated PCA3 as a requirement for biopsies in addition to PSA would have saved 37 (cutoff ≥ 25) or 43 (cutoff ≥ 35) of the 68 biopsy sessions, and 7 or 11 PCs would have been missed, respectively, including multiple high-risk PCs. So far, PCA3 performed best among BRCA2 mutation carriers, but the numbers are still small. Because PCA3 was not used to indicate prostate biopsies, its true diagnostic value cannot be calculated. CONCLUSIONS: The results do not provide evidence for PCA3 as a useful additional indicator of prostate biopsies in BRCA mutation carriers, as many participants had an elevated PCA3 in the absence of PC. This must be interpreted with caution because PCA3 was not used to indicate biopsies. Many participants diagnosed with PC had low PCA3, making it invalid as a restrictive marker for prostate biopsies in men with elevated PSA levels.


Assuntos
Biomarcadores Tumorais/urina , Neoplasias da Mama Masculina/genética , Antígeno Prostático Específico/urina , Neoplasias da Próstata/genética , Idoso , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias da Próstata/patologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-25756382

RESUMO

Unsafe practices are an underestimated contributor to the disease burden of bloodborne viruses. Outbreaks associated with failures in basic infection prevention have been identified in nonhospital settings with increased frequency in the United States during the past 15 years, representing an alarming trend and indicating that the challenge of providing consistently safe care is not always met. As has been the case with most medical specialties, there have been public health investigations by state and local health departments, and the Centers for Disease Control and Prevention have identified some instances of unsafe practices that have placed podiatric medical patients at risk for viral, bacterial, and fungal infections. All health-care providers, including podiatric physicians, must make infection prevention a priority in any setting in which care is delivered.

19.
Eur Urol ; 68(2): 186-93, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25454609

RESUMO

BACKGROUND: Germline BRCA mutations are associated with worse prostate cancer (PCa) outcomes; however, the most appropriate management for mutation carriers has not yet been investigated. OBJECTIVE: To evaluate the response of BRCA carriers to conventional treatments for localised PCa by analysing metastasis-free survival (MFS) and cause-specific survival (CSS) following radical prostatectomy (RP) or external-beam radiation therapy (RT). DESIGN, SETTING, AND PARTICIPANTS: Tumour features and outcomes of 1302 patients with local/locally advanced PCa (including 67 BRCA mutation carriers) were analysed. RP was undergone by 535 patients (35 BRCA); 767 received RT (32 BRCA). Median follow-up was 64 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Median survival and 3-, 5-, and 10-yr survival rates were estimated using the Kaplan-Meier method. Generated survival curves were compared using the log-rank test. Cox regression analyses were used to assess the prognostic value of BRCA mutations. RESULTS AND LIMITATIONS: A total of 67 BRCA carriers and 1235 noncarriers were included. At 3, 5, and 10 yr after treatment, 97%, 94%, and 84% of noncarriers and 90%, 72%, and 50% of carriers were free from metastasis (p<0.001). The 3-, 5- and 10-yr CSS rates were significantly better in the noncarrier cohort (99%, 97%, and 85%, respectively) than in carriers (96%, 76%, and 61%, respectively; p<0.001). Multivariate analysis confirmed BRCA mutations as an independent prognostic factor for MFS (hazard ratio [HR]: 2.36; 95% confidence interval [CI], 1.38-4.03; p=0.002) and CSS (HR: 2.17; 95% CI, 1.16-4.07; p=0.016). CONCLUSIONS: BRCA carriers had worse outcomes than noncarriers when conventionally treated for local/locally advanced PCa. PATIENT SUMMARY: Prostate cancer patients with germline BRCA mutations had worse outcomes than noncarriers when conventionally treated with surgery or radiation therapy.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Mutação em Linhagem Germinativa , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Análise Mutacional de DNA , Intervalo Livre de Doença , Predisposição Genética para Doença , Humanos , Calicreínas/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Fenótipo , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Prostatectomia/mortalidade , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Reino Unido
20.
Fam Cancer ; 13(4): 625-35, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24980079

RESUMO

A family history of prostate cancer (PC) is one of the main risk factors for the disease. A number of common single nucleotide polymorphisms (SNPs) that confer small but cumulatively substantial risks of PC have been identified, opening the possibility for the use of SNPs in PC risk stratification for targeted screening and prevention in the future. The objective of this study was to explore the psychosocial impact of receiving information about genetic risk of PC. The participants were men who had a family history of PC and were enrolled in a screening study providing research genetic profiling alongside screening for PC. A combination of questionnaires and in-depth interviews were used. Questionnaires were completed by men at two time points: both before and after joining the study and going through the genetic profiling process. The interviews were completed after all study process were complete and were analysed using a framework analysis. In total 95 men completed both questionnaires and 26 men were interviewed. A number of issues facing men at risk of PC were identified. The results fell into two main categories: personal relevance and societal relevance. The strength of men's innate beliefs about their risk, shaped by genetic and environmental assumptions, outweigh the information provided by genetic testing. Men felt genetic profile results would have future use for accessing prostate screening, being aware of symptoms and in communicating with others. The findings reinforce the importance of providing contextual information alongside genetic profiling test results, and emphasises the importance of the counselling process in providing genetic risk information. This research raises some key issues to facilitate clinical practice and future research related to the use of genetic profiling to determine risk of PC and other diseases.


Assuntos
Predisposição Genética para Doença/genética , Predisposição Genética para Doença/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Neoplasias da Próstata/genética , Neoplasias da Próstata/psicologia , Adulto , Idoso , Perfilação da Expressão Gênica , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Inquéritos e Questionários
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