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1.
Prostate ; 84(11): 993-1015, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38682886

RESUMO

INTRODUCTION: The 2023 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, themed "Disrupting Prostate Cancer Research: Challenge Accepted," was convened at the University of California, Los Angeles, Luskin Conference Center, in Los Angeles, CA, from June 22 to 25, 2023. METHODS: The 2023 marked the 10th Annual CHPCA Meeting, a discussion-oriented scientific think-tank conference convened annually by the Prostate Cancer Foundation, which centers on innovative and emerging research topics deemed pivotal for advancing critical unmet needs in prostate cancer research and clinical care. The 2023 CHPCA Meeting was attended by 81 academic investigators and included 40 talks across 8 sessions. RESULTS: The central topic areas covered at the meeting included: targeting transcription factor neo-enhancesomes in cancer, AR as a pro-differentiation and oncogenic transcription factor, why few are cured with androgen deprivation therapy and how to change dogma to cure metastatic prostate cancer without castration, reducing prostate cancer morbidity and mortality with genetics, opportunities for radiation to enhance therapeutic benefit in oligometastatic prostate cancer, novel immunotherapeutic approaches, and the new era of artificial intelligence-driven precision medicine. DISCUSSION: This article provides an overview of the scientific presentations delivered at the 2023 CHPCA Meeting, such that this knowledge can help in facilitating the advancement of prostate cancer research worldwide.


Assuntos
Pesquisa Biomédica , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Pesquisa Biomédica/tendências
2.
Prostate ; 84(10): 954-958, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641986

RESUMO

BACKGROUND: Poly ADP-ribose polymerase (PARP) inhibitors are approved for the treatment of some men with advanced prostate cancer. Rare but serious side effects include myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The impact of PARP inhibitors on clonal hematopoiesis (CH), a potential precursor lesion associated with MDS and AML, is incompletely understood in prostate cancer. We hypothesized that PARP inhibitors would increase CH prevalence and abundance. METHODS: We prospectively enrolled participants with advanced prostate cancer treated with PARP inhibitors. The presence of CH was assessed from leukocytes using an ultra-deep error-corrected dual unique molecular identifiers sequencing method targeting 49 genes most commonly mutated in CH and myeloid malignancies. Variant allele frequencies (VAF) of ≥0.5% were considered clinically significant. Blood samples were collected before and after PARP inhibitor treatment. RESULTS: Ten men were enrolled; mean age of 67 years. Six patients had Gleason 7 disease, and four had Gleason ≥8 disease at diagnosis. Nine had localized disease at diagnosis, and eight had prior treatment with radiation. The mean time between pre- and post-treatment blood samples was 11 months (range 2.6-31 months). Six patients (60%) had CH identified prior to PARP inhibitor treatment, three with multiple clones. Of 11 CH clones identified in follow-up, 5 (45%) appeared or increased after treatment. DNMT3A, TET2, and PPM1D were the most common CH alterations observed. The largest post-treatment increase involved the PPM1D gene. CONCLUSION: CH alterations are frequently found after treatment with PARP inhibitors in patients with prostate cancer and this may be one mechanism by which PARP inhibitors lead to increased risk of MDS/AML.


Assuntos
Hematopoiese Clonal , Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Humanos , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Idoso , Pessoa de Meia-Idade , Hematopoiese Clonal/genética , Estudos Prospectivos , Progressão da Doença , Prevalência , Idoso de 80 Anos ou mais , Proteínas de Ligação a DNA , Dioxigenases
3.
Oncologist ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885246

RESUMO

BACKGROUND: The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate. RESULTS: Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected. CONCLUSION: Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice.

4.
Emerg Infect Dis ; 28(7): 1527-1530, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35483111

RESUMO

Epidemiologic and genomic investigation of SARS-CoV-2 infections associated with 2 repatriation flights from India to Australia in April 2021 indicated that 4 passengers transmitted SARS-CoV-2 to >11 other passengers. Results suggest transmission despite mandatory mask use and predeparture testing. For subsequent flights, predeparture quarantine and expanded predeparture testing were implemented.


Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/epidemiologia , Genoma Viral , Genômica , Humanos , Quarentena , SARS-CoV-2/genética
5.
Prostate ; 82(2): 260-268, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34783071

RESUMO

BACKGROUND: Inactivating missense mutations in the SPOP gene, encoding speckle-type poxvirus and zinc-finger protein, are one of the most common genetic alterations in prostate cancer. METHODS: We retrospectively identified 72 consecutive prostate cancer patients with somatic SPOP mutations, through next-generation sequencing analysis, who were treated at the Johns Hopkins Hospital. We evaluated clinical and genomic characteristics of this SPOP-mutant subset. RESULTS: SPOP alterations were clustered in the MATH domain, with hotspot mutations involving the F133 and F102 residues. The most frequent concurrent genetic alterations were in APC (16/72 [22%]), PTEN (13/72 [18%]), and TP53 (11/72 [15%]). SPOP-mutant cancers appeared to be mutually exclusive with tumors harboring the TMPRSS2-ERG fusion, and were significantly enriched for Wnt pathway (APC, CTNNB1) mutations and de-enriched for TP53/PTEN/RB1 alterations. Patients with mtSPOP had durable responses to androgen deprivation therapy (ADT) with a median time-to-castration-resistance of 42.0 (95% confidence interval [CI], 25.7-60.8) months. However, time-to-castration-resistance was significantly shorter in SPOP-mutant patients with concurrent TP53 mutations (hazard ratio [HR] 4.53; p = 0.002), HRD pathway (ATM, BRCA1/2, and CHEK2) mutations (HR 3.19; p = 0.003), and PI3K pathway (PTEN, PIK3CA, and AKT1) alterations (HR 2.69; p = 0.004). In the castration-resistant prostate cancer setting, median progression-free survival was 8.9 (95% CI, 6.7-NR) months on abiraterone and 7.3 (95% CI, 3.2-NR) months on enzalutamide. There were no responses to PARP inhibitor treatment. CONCLUSIONS: SPOP-mutant prostate cancers represent a unique subset with absent ERG fusions and frequent Wnt pathway alterations, with potentially greater dependency on androgen signaling and enhanced responsiveness to ADT. Outcomes are best for SPOP-altered patients without other concurrent mutations.


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Proteínas Nucleares/genética , Neoplasias da Próstata , Proteínas Repressoras/genética , Serina Endopeptidases/genética , Progressão da Doença , Fusão Gênica/fisiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Intervalo Livre de Progressão , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Regulador Transcricional ERG/genética , Resultado do Tratamento , Via de Sinalização Wnt/fisiologia
6.
Prostate ; 81(16): 1382-1389, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34516663

RESUMO

BACKGROUND: Among men with metastatic prostate cancer, about 10% have germline alterations in DNA damage response genes. Most studies have examined BRCA2 alone or an aggregate of BRCA1/2 and ATM. Emerging data suggest that ATM mutations may have distinct biology and warrant individual evaluation. The objective of this study is to determine whether response to prostate cancer systemic therapies differs between men with germline mutations in ATM (gATM) and BRCA2 (gBRCA2). METHODS: This is an international multicenter retrospective matched cohort study of men with prostate cancer harboring gATM or gBRCA2. PSA50 response (≥50% decline in prostate-specific antigen) was compared using Fisher's exact test. RESULTS AND LIMITATIONS: The study included 45 gATM and 45 gBRCA2 patients, matched on stage and year of germline testing. Patients with gATM and gBRCA2 had similar age, Gleason grade, and PSA at diagnosis. We did not observe differences in PSA50 responses to abiraterone, enzalutamide, or docetaxel in metastatic castration resistant prostate cancer between the two groups; however, 0/7 with gATM and 12/14 with gBRCA2 achieved PSA50 response to PARPi (p < .001). Median (95% confidence interval) overall survival from diagnosis to death was 10.9 years (9.5-not reached) versus 9.9 years (7.1-not reached, p = .07) for the gATM and gBRCA2 cohorts, respectively. Limitations include the retrospective design and lack of mutation zygosity data. CONCLUSIONS: Conventional therapies can be effective in gATM carriers and should be considered before PARPi, which shows limited efficacy in this group. Men with gATM mutations warrant prioritization for novel treatment strategies.


Assuntos
Androstenos/uso terapêutico , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA2/genética , Benzamidas/uso terapêutico , Docetaxel/uso terapêutico , Conduta do Tratamento Medicamentoso/normas , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Próstata Resistentes à Castração , Antineoplásicos/uso terapêutico , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Seleção de Pacientes , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Estudos Retrospectivos , Análise de Sobrevida
7.
Cancer ; 127(11): 1864-1870, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33561293

RESUMO

BACKGROUND: The relation between cardiorespiratory fitness (CRF) and prostate cancer is not well established. The objective of this study was to determine whether CRF is associated with prostate cancer screening, incidence, or mortality. METHODS: The Henry Ford Exercise Testing Project is a retrospective cohort study of men aged 40 to 70 years without cancer who underwent physician-referred exercise stress testing from 1995 to 2009. CRF was quantified in metabolic equivalents of task (METs) (<6 [reference], 6-9, 10-11, and ≥12 METs), estimated from the peak workload achieved during a symptom-limited, maximal exercise stress test. Prostate-specific antigen (PSA) testing, incident prostate cancer, and all-cause mortality were analyzed with multivariable adjusted Poisson regression and Cox proportional hazard models. RESULTS: In total, 22,827 men were included, of whom 739 developed prostate cancer, with a median follow-up of 7.5 years. Men who had high fitness (≥12 METs) had an 28% higher risk of PSA screening (95% CI, 1.2-1.3) compared with those who had low fitness (<6 METs. After adjusting for PSA screening, fitness was associated with higher prostate cancer incidence (men aged <55 years, P = .02; men aged >55 years, P ≤ .01), but not with advanced prostate cancer. Among the men who were diagnosed with prostate cancer, high fitness was associated with a 60% lower risk of all-cause mortality (95% CI, 0.2-0.9). CONCLUSIONS: Although men with high fitness are more likely to undergo PSA screening, this does not fully account for the increased incidence of prostate cancer seen among these individuals. However, men with high fitness have a lower risk of death after a prostate cancer diagnosis, suggesting that the cancers identified may be low-risk with little impact on long-term outcomes.


Assuntos
Aptidão Cardiorrespiratória , Neoplasias da Próstata , Adulto , Idoso , Detecção Precoce de Câncer/estatística & dados numéricos , Teste de Esforço , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos
8.
J Urol ; 206(3): 623-629, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34003011

RESUMO

PURPOSE: There were 3 recent U.S. Food and Drug Administration approvals for drugs to be used in nonmetastatic castration resistant prostate cancer, a state that arises from the unproven start of continuous androgen deprivation therapy (ADT) for biochemical recurrent prostate cancer (BCR), before metastatic disease is evident. This report examines the outcome of men with BCR who defer ADT until time of metastasis. MATERIALS AND METHODS: Retrospective review of men diagnosed with clinically localized prostate cancer who underwent radical prostatectomy at Johns Hopkins Hospital and Walter Reed National Military Medical Center and developed BCR with a prostate specific antigen doubling time of not more than 10 months (806 patients). The primary end points were metastasis-free survival and overall survival from time of local treatment among men who delayed ADT until time of metastasis. RESULTS: The median metastasis-free survival of men with BCR and a prostate specific antigen doubling time <6 months and 10 months who delay ADT until metastasis is 144 months (95% CI 48-not reached) and 192 months (95% CI 72-not reached), respectively, with a median overall survival of 168 months (95% CI 96-276 months) and 204 months (95% CI 120-276), respectively. CONCLUSIONS: Metastasis-free survival and overall survival of men with BCR who delay hormone therapy is long. This underscores the need to reevaluate when to start primary ADT in this patient population.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Calicreínas/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapia , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Quimioterapia Adjuvante/métodos , Tomada de Decisão Clínica , Progressão da Doença , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Guias de Prática Clínica como Assunto , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/normas
9.
BJU Int ; 128(3): 366-373, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33765326

RESUMO

OBJECTIVE: To investigate whether bipolar androgen therapy (BAT), involving rapid cyclic administration of high-dose testosterone, as a novel treatment for metastatic castration-resistant prostate cancer (mCRPC) promotes improvements in body composition and associated improvements in lipid profiles and quality of life. PATIENTS AND METHODS: Men from two completed trials with computed tomography imaging at baseline and after three cycles of BAT were included. Cross-sectional areas of psoas muscle, visceral and subcutaneous fat were measured at the L3 vertebral level. Functional Assessment of Chronic Illness Therapy - Fatigue questionnaire and 36-item short-form health survey were used to assess quality of life. RESULTS: The 60 included patients lost a mean (sd) of 7.8 (8.2)% of subcutaneous fat, 9.8 (18.2)% of visceral fat, and gained 12.2 (6.7)% muscle mass. Changes in subcutaneous and visceral fat were positively correlated with each other (Spearman's correlation coefficient 0.58, 95% confidence interval 0.35-0.71) independent of the effects of age, body mass index, and duration of androgen-deprivation therapy. Energy, physical function, and measures of limitations due to physical health were all significantly improved at 3 months. The improvements in body composition were not correlated with decreases in lipid levels or observed improvements in quality of life. CONCLUSIONS: In the present study, BAT was associated with significant improvements in body composition, lipid parameters, and quality of life. This has promising implications for the long-term health of men with mCRPC.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Androgênios/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Testosterona/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Composição Corporal , Humanos , Metabolismo dos Lipídeos , Masculino , Pessoa de Meia-Idade , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/fisiopatologia , Qualidade de Vida
10.
BMC Infect Dis ; 21(1): 584, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134657

RESUMO

BACKGROUND: The demographic of Northern Territory prison population differs than elsewhere in Australia and the prevalence of hepatitis B and hepatitis C may therefore be somewhat different from other jurisdictions. There has been no study which has specifically described the serological results of a large proportion of prisoners in Northern Territory correctional facilities over an extended period of time. METHODS: This retrospective longitudinal study reviewed serological results and testing rates for hepatitis B, and hepatitis C performed in correctional facilities in the Northern Territory of Australia between July 1st, 2003 and June 30th, 2017. RESULTS: The proportion of positive records over 14 years for hepatitis B surface antigen (HBsAg) was 641/12,066 (5.3, 95% CI 4.9-5.7), for hepatitis B core antibody (anti-HBc) 4937/12,138 (40.1, 95%CI 39.8-41.6), for hepatitis B surface antibody (anti-HBs) 6966/13,303 (52.4, 95% CI 51.5-53.2), and for hepatitis C antibody 569/12,153 (4.7, 95% CI 4.3-5.1). The proportion of prisoners tested for hepatitis B and hepatitis C has decreased since 2015, while a high proportion of prisoners remain non-immune to hepatitis B. CONCLUSION: There is a relatively high proportion of positive serological markers of hepatitis B, and a lower proportion of positive hepatitis C serology in the Northern Territory's correctional facilities compared to overall Australian rates. As the proportion of prisoners tested for hepatitis B and C has decreased recently, and a high proportion of prisoners remain non-immune to hepatitis B, there are opportunities to increase testing and vaccination rates in this population.


Assuntos
Hepatite B/diagnóstico , Hepatite C/diagnóstico , Adulto , Biomarcadores/sangue , Estabelecimentos Correcionais/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Northern Territory/epidemiologia , Prevalência , Estudos Retrospectivos , Adulto Jovem
11.
J Cancer Educ ; 36(2): 431-434, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32500454

RESUMO

The author describes her impetus and journey in developing Un Abrazo Para La Familia™ [Embracing the Family] (Abrazo), 3 hours of cancer information presented in an educational and modular format and designed for low-income informal caregivers who are co-survivors of cancer. A rehabilitation-informed preventive intervention, Abrazo reflects the importance of family, culture, and socioeconomic background in its approach.


Assuntos
Neoplasias , Pais , Cuidadores , Feminino , Humanos , Pobreza , Sobreviventes
12.
J Cancer Educ ; 36(2): 294-298, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-31776893

RESUMO

This exploratory pilot study aims to provide preliminary data describing the experiences of university student cancer survivors, quantify their connection to the campus Disability Resource Center, and assess the feasibility of conducting research with this population. In this descriptive study of cancer survivor students at one large university in the southwestern U.S., online survey respondents with a history of cancer (N = 19) reported cognitive, emotional, and physical limitations that affected their educational experience. The majority (78.9%) of our participants were children, adolescents, or young adults (up to age 39) when diagnosed with cancer; all others were diagnosed between 40 and 60 years old. We found that students living with cancer have short- and long-term impairments, including memory issues that made academic performance difficult. These effects led some students to cope individually while others sought support from institutional entities or instructors. Here we document survivor experiences and propose next steps in research, which includes an intervention that builds on our preliminary findings and uses the positive deviance model.


Assuntos
Sobreviventes de Câncer , Neoplasias , Adolescente , Adulto , Criança , Humanos , Projetos Piloto , Estudantes , Inquéritos e Questionários , Universidades , Adulto Jovem
13.
J Cancer Educ ; 36(5): 1075-1080, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32239477

RESUMO

Un Abrazo Para La Familia™ (Abrazo) is a 3-h modular preventive intervention designed for low-income caregivers who are co-survivors of cancer. Here we (1) consider the benefit to survivors of cancer, that is, the care recipients who participate in Abrazo; (2) summarize the literature specific to research outreach to low-income, underserved populations when they are faced with cancer; and (3) describe current steps being taken in Southern Arizona to reach these populations via Abrazo. Specific to considering the benefit to care recipients, we analyzed care recipient data derived from three existing cohorts of Abrazo participants. Analyses of the combined cohorts of these data demonstrate that Abrazo is effective with care recipients given statistically significant higher cancer knowledge and self-efficacy scores, pre- vs. post-intervention. We can now report benefit to care recipients who participate in Abrazo. This allows us, with confidence, to expand research recruitment efforts to include care recipients as part of the Abrazo intervention in our efforts to serve low-income, underserved populations when faced with cancer.


Assuntos
Neoplasias , Sobreviventes , Cuidadores , Humanos , Pobreza , Populações Vulneráveis
14.
Curr Opin Oncol ; 32(3): 216-222, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32168038

RESUMO

PURPOSE OF REVIEW: The present article highlights the most common DNA repair gene mutations, using specific examples of individual genes or gene classes, and reviews the epidemiology and treatment implications for each one [with particular emphasis on poly-ADP-ribose polymerase (PARP) inhibition and PD-1 blockade]. RECENT FINDINGS: Genetic and genomic testing have an increasingly important role in the oncology clinic. For patients with prostate cancer, germline genetic testing is now recommended for all men with high-risk and metastatic disease, and somatic multigene tumor testing is recommended for men with metastatic castration-resistant disease. The most common mutations that are present in men with advanced prostate cancer are in genes coordinating DNA repair and the DNA damage response. SUMMARY: Although much of what is discussed currently remains investigational, it is clear that genomically-targeted treatments will become increasingly important for patients with prostate cancer in the near future and beyond.


Assuntos
Dano ao DNA , Reparo do DNA , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Antineoplásicos Hormonais/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Testes Genéticos , Humanos , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Ann Intern Med ; 171(10): 756-764, 2019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31569235

RESUMO

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Description: Dietary guideline recommendations require consideration of the certainty in the evidence, the magnitude of potential benefits and harms, and explicit consideration of people's values and preferences. A set of recommendations on red meat and processed meat consumption was developed on the basis of 5 de novo systematic reviews that considered all of these issues. Methods: The recommendations were developed by using the Nutritional Recommendations (NutriRECS) guideline development process, which includes rigorous systematic review methodology, and GRADE methods to rate the certainty of evidence for each outcome and to move from evidence to recommendations. A panel of 14 members, including 3 community members, from 7 countries voted on the final recommendations. Strict criteria limited the conflicts of interest among panel members. Considerations of environmental impact or animal welfare did not bear on the recommendations. Four systematic reviews addressed the health effects associated with red meat and processed meat consumption, and 1 systematic review addressed people's health-related values and preferences regarding meat consumption. Recommendations: The panel suggests that adults continue current unprocessed red meat consumption (weak recommendation, low-certainty evidence). Similarly, the panel suggests adults continue current processed meat consumption (weak recommendation, low-certainty evidence). Primary Funding Source: None. (PROSPERO 2017: CRD42017074074; PROSPERO 2018: CRD42018088854).


Assuntos
Dieta/normas , Produtos da Carne , Política Nutricional , Carne Vermelha , Doenças Cardiovasculares/epidemiologia , Humanos , Neoplasias/epidemiologia
16.
Cancer ; 125(15): 2594-2601, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31056756

RESUMO

BACKGROUND: To the authors' knowledge, the relationship between cardiorespiratory fitness (CRF) and lung and colorectal cancer outcomes is not well established. METHODS: A retrospective cohort study was performed of 49,143 consecutive patients who underwent clinician-referred exercise stress testing from 1991 through 2009. The patients ranged in age from 40 to 70 years, were without cancer, and were treated within the Henry Ford Health System in Detroit, Michigan. CRF, measured in metabolic equivalents of task (METs), was categorized as <6 (reference), 6 to 9, 10 to 11, and ≥12. Incident cancer was obtained through linkage to the cancer registry and all-cause mortality from the National Death Index. RESULTS: Participants had a mean age of 54 ± 8 years. Approximately 46% were female, 64% were white, 29% were black, and 1% were Hispanic. The median follow-up was 7.7 years. Cox proportional hazard models, adjusted for age, race, sex, body mass index, smoking history, and diabetes, found that those in the highest fitness category (METs ≥12) had a 77% decreased risk of lung cancer (hazard ratio [HR], 0.23; 95% CI, 0.14-0.36) and a 61% decreased risk of incident colorectal cancer (HR, 0.39; 95% CI, 0.23-0.66; with additional adjustment for aspirin and statin use). Among those diagnosed with lung and colorectal cancer, those with high fitness had a decreased risk of subsequent death of 44% and 89%, respectively (HR, 0.56 [95% CI, 0.32-1.00] and HR, 0.11 [95% CI, 0.03-0.37], respectively). CONCLUSIONS: In what to the authors' knowledge is the largest study performed to date, higher CRF was associated with a lower risk of incident lung and colorectal cancer in men and women and a lower risk of all-cause mortality among those diagnosed with lung or colorectal cancer.


Assuntos
Aptidão Cardiorrespiratória/fisiologia , Neoplasias Colorretais/etiologia , Teste de Esforço/métodos , Neoplasias Pulmonares/etiologia , Idoso , Estudos de Coortes , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
18.
BMC Emerg Med ; 19(1): 74, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771517

RESUMO

BACKGROUND: The rapid identification of deterioration in the pediatric population is complex, particularly in the emergency department (ED). A comprehensive multi-faceted Pediatric Early Warning System (PEWS) might maximize early recognition of clinical deterioration and provide a structured process for the reassessment and escalation of care. The objective of the study was to evaluate the implementation fidelity, effectiveness, and utility of a 5-component PEWS implemented in the ED of an urban public general hospital in British Columbia, Canada, and to guide provincial scale up. METHODS: We used a before-and-after design to evaluate the implementation fidelity, effectiveness, and utility of a 5-component PEWS (pediatric assessment flowsheet, PEWS score, situational awareness, escalation aid, and communication framework). Sources of data included patient medical records, surveys of direct care staff, and key-informant interviews. Data were analyzed using mixed-methods approaches. RESULTS: The majority of medical records had documented PEWS scores at triage (80%) and first bedside assessment (81%), indicating that the intervention was implemented with high fidelity. The intervention was effective in increasing vital signs documentation, both at first beside assessment (84% increase) and throughout the ED stay (> 100% increase), in improving staff's self-perceived knowledge and confidence in providing pediatric care, and self-reported communication between staff. Satisfaction levels were high with the PEWS scoring system, flowsheet, escalation aid, and to a lesser extent with the situational awareness tool and communication framework. Reasons for dissatisfaction included increased paperwork and incidence of false-positives. Overall, the majority of providers indicated that implementation of PEWS and completing a PEWS score at triage alongside the Canadian Triage and Acuity Scale (CTAS) added value to pediatric care in the ED. Results also suggest that the intervention is aligned with current practice in the ED. CONCLUSION: Our study shows that high-fidelity implementation of PEWS in the ED is feasible. We also show that a multi-component PEWS can be effective in improving pediatric care and be well-accepted by staff. Results and lessons learned from this pilot study are being used to scale up implementation of PEWS in ED settings across the province of British Columbia.


Assuntos
Deterioração Clínica , Serviço Hospitalar de Emergência/organização & administração , Adolescente , Colúmbia Britânica , Criança , Pré-Escolar , Competência Clínica/normas , Comunicação , Documentação/normas , Diagnóstico Precoce , Hospitais Públicos/organização & administração , Humanos , Lactente , Recém-Nascido , Gravidade do Paciente , Projetos Piloto , Curva ROC , Estudos Retrospectivos , Triagem/organização & administração , Sinais Vitais
19.
Psychooncology ; 27(10): 2405-2411, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30047167

RESUMO

OBJECTIVE: Our goal in this study was to determine if we could replicate initial findings when providing the intervention, Un Abrazo Para La Familia ("Abrazo"). Abrazo is a community-focused psychoeducational preventive intervention addressing the cancer information and coping needs of low-income, underserved family members of cancer survivors, developed and first implemented in Tucson, Arizona. METHODS: We used a preintervention and postintervention evaluation design to assess the effectiveness of replicating the Abrazo intervention with underserved Hispanic/Latino family members facing cancer as co-survivors. We describe lessons learned in an expansion of Abrazo from one region of the United States to another. RESULTS: Portland promotoras demonstrated that when the Abrazo intervention is provided via a culturally congruent, accessible format, the significant gains in cancer knowledge and self-efficacy reported by underserved co-survivors can be replicated. This is important because Oregon represents a US region different from Abrazo's origins in the Southwest. CONCLUSION: Our replication study provides a useful roadmap for others focusing on the psychosocial needs of Hispanic/Latino cosurviving family members of cancer. A manualized 12-hour training program based on the initial discovery and efficacy work was developed to train promotoras as a part of this study. The manual provides a clear protocol for others to replicate our intervention and evaluation procedures. Abrazo may be particularly important for family-centered care if the family does not have the cancer knowledge or self-confidence needed to fully participate.


Assuntos
Adaptação Psicológica , Sobreviventes de Câncer/psicologia , Família/psicologia , Hispânico ou Latino/psicologia , Área Carente de Assistência Médica , Neoplasias/psicologia , Populações Vulneráveis , Adolescente , Adulto , Criança , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Oregon , Pais , Pobreza , Autoeficácia , Estados Unidos
20.
BMC Med Res Methodol ; 18(1): 162, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518328

RESUMO

BACKGROUND: Recent systematic reviews and editorials suggest that many organizations that produce nutritional guideline recommendations do not adhere to internationally recognized standards set forth by the Institute of Medicine (IoM), Guidelines International Network (GIN), Appraisal of Guidelines Research and Evaluation (AGREE), and Grading Recommendations, Assessment, Development and Evaluation (GRADE). METHODS: The potential solution is an independent group with content expertise and skilled in the methodology of systematic reviews and practice guidelines to produce trustworthy guideline recommendations, recommendations that are supported by publication in a top tier journal. The BMJ Rapid Recommendations project has recently demonstrated the feasibility and utility of this approach. Here, we are proposing trustworthy nutritional guideline recommendations based on internationally accepted guideline development standards, recommendations that will be informed by rigorous and novel systematic reviews of the benefits and harms associated with nutritional exposures, as well as studies on the values and preferences related to dietary behaviors among members of the international community. DISCUSSION: Adhering to international guideline standards, conducting high quality systematic reviews, and actively assessing the values and preferences of key stakeholders is expected to improve the quality of nutritional guidelines and their relevance to end-users, particularly patients and community members. We will send our work for peer review, and if found acceptable, we will publish our nutritional recommendations in top-tier general medicine journals.


Assuntos
Medicina Baseada em Evidências/normas , Necessidades Nutricionais , Guias de Prática Clínica como Assunto/normas , Revisões Sistemáticas como Assunto , Medicina Baseada em Evidências/métodos , Humanos , Internacionalidade , Revisão por Pares/normas
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