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1.
Psychol Serv ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436647

RESUMO

Transgender and gender diverse (TGD) veterans in the Veterans Health Administration experience health and health care disparities, and research with this population is needed to improve gender-affirming care in Veterans Health Administration. However, TGD veterans may experience hesitancy to participate in research. We must address barriers to participation through feasible and acceptable methods. Opt-out letters are an effective tool used to recruit veterans in mental health research. The present study examined the feasibility and acceptability of opt-out letters modified for TGD veterans. Opt-out letters were sent to 54 potential TGD participants at three sites. The letters stated the research team would begin contacting veterans by phone in 2 weeks if they did not opt out of being contacted. Feasibility was measured through response rate. Acceptability was assessed through qualitative template analysis of interview data. Of the 54 potential participants, two opted out, three letters were undeliverable, and eight veterans called to opt in. Veterans reported that they found the letters to be clear and useful. The responses to the opt-out letters resulted in completing recruitment for two of the three sites. The research team then called the veterans who received the letter at the third site (three veterans) and recruited one additional veteran, for a total of nine TGD veterans. Opt-out letters may be a helpful tool to recruit TGD veterans to participate in research. Although these letters were designed to opt out, 89% of participants called the research team to opt in. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
Front Health Serv ; 3: 1124290, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37560195

RESUMO

Introduction: Engaging service users or consumers in quality improvement or implementing a new service is important across settings and may reduce health inequities. Implementation strategies leveraging consumer engagement are neither commonly used nor robustly operationalized in implementation science. Implementers (e.g., middle managers, facilitators) want to involve consumers in implementation activities, but do not always feel confident in how to proceed. We developed a compendium of tools called Consumer Voice to guide others how to engage consumers in design/delivery of implementation strategies. Although generalizable to other settings, we developed Consumer Voice within the context of implementing suicide prevention treatments in healthcare to reach rural U.S. military veterans, as there are suicide inequities for people in rural areas. Methods: We developed Consumer Voice using a multistep process and human-centered design methods. In between steps, a design team met to generate insights from data, and decide which prototypes to create/refine. In preliminary work, we conducted a scan of examples in healthcare of patient engagement in implementation activities and interviewed two implementation experts about preferred learning styles. In Step 1, we interviewed 26 participants with experience in community engagement, implementation, or lived experience as a rural U.S. veteran with suicidal thoughts/behavior. In Step 2, 11 implementers beta tested prototypes then share feedback in focus groups. In Step 3, we reconvened participants from prior steps to review tools and, using nominal group technique, prioritized remaining recommendations. Results: Consumer Voice is online, modular, and nonlinear for self-guided learning tailored to beginner, intermediate, or advanced experience with consumer engagement. Tools consist of slides, audiovisual content with written text, and templates. Findings indicated there is not one "right" way to engage consumers in implementation activities, rather that implementers wanted tools showcasing core principles for consumer engagement and practical ideas. Discussion: Consumer Voice can be used by implementers to reflect and decide on how to apply consumer engagement implementation strategies to improve equitable dissemination and uptake of evidence-based practices. Most insights generated by user data were explicitly to build trust between consumers and professionals representing institutions, which may be one component to reducing healthcare inequities.

3.
Front Public Health ; 11: 1251565, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38352130

RESUMO

Background: In the United States Department of Veterans Affairs (VA), veterans who are lesbian, gay, bisexual, transgender, queer, and similar gender and sexual minoritized people (LGBTQ+) experience health disparities compared to cisgender, heterosexual veterans. VA's LGBTQ+ Health Program created two healthcare policies on providing LGBTQ+ affirming care (healthcare that is inclusive, validating, and understanding of the LGBTQ+ population). The current project examines providers' barriers and facilitators to providing LGBTQ+ affirming care and LGBTQ+ veterans' barriers and facilitators to receiving LGBTQ+ affirming care. Methods: Data collection and analysis were informed by the Consolidated Framework for Implementation Research, which was adapted to include three health equity domains. Data collection involved telephone interviews conducted with 11 VA providers and 12 LGBTQ+ veterans at one rural and one urban VA medical center, and one rural VA community clinic. Qualitative data were rapidly analyzed using template analysis, a data reduction technique. Results: Providers described limited education, limited time, lack of experience with the population, and a lack of awareness of resources as barriers. Providers discussed comfort with consulting trusted peers, interest in learning more about providing LGBTQ+ affirming care, and openness and acceptance of the LGBTQ+ community as facilitators. LGBTQ+ veterans described a lack of provider awareness of their needs, concerns related to safety and discrimination, and structural discrimination as barriers. LGBTQ+ veterans described positive relationships with providers, knowledge of their own healthcare needs, and ability to advocate for their healthcare needs as facilitators. Although VA's LGBTQ+ affirming care policies are in place, providers and veterans noted a lack of awareness regarding specific healthcare processes. Conclusion: Allowing more time and capacity for education and engaging LGBTQ+ veterans in determining how to improve their healthcare may be the path forward to increase adherence to LGBTQ+ affirming care policies. Engaging patients, especially those from marginalized backgrounds, in strategies focused on the uptake of policy may be a path to improve policy implementation. It is possible that creating truly collaborative structures in which patients, staff, providers, leadership, and policymakers can work together towards policy implementation may be a useful strategy. In turn, improved policy implementation would result in increased physical and mental health for LGBTQ+ veterans.


Assuntos
Minorias Sexuais e de Gênero , Saúde dos Veteranos , Feminino , Humanos , Estados Unidos , Atenção à Saúde , Comportamento Sexual , Políticas
4.
BMC Health Serv Res ; 22(1): 731, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650573

RESUMO

BACKGROUND: A recent paradigm shift has led to an explicit focus on enhancing health equity through equity-oriented dissemination and implementation (D&I) research. However, the integration and bidirectional learning across these two fields is still in its infancy and siloed. This exploratory study aimed to examine participants' perceived capabilities, opportunities, and motivations to conduct equity-oriented D&I research. METHODS: We conducted an exploratory cross-sectional survey distributed online from December 2020 to April 2021. Participants were recruited at either D&I or health disparities-oriented conferences, meetings, through social media, or personal outreach via emails. Informed by the Capability, Opportunity, and Motivation Model (COM-B), the survey queried respondents about different aspects of engaging in and conducting equity-oriented D&I research. All analyses were conducted in SPSS Version 27.0. RESULTS: A total of 180 participants responded to the survey. Most participants were women (81.7%), white (66.1%), academics (78.9%), and faculty members (53.9%). Many reported they were advanced (36.7%) or advanced beginners (27.8%) in the D&I field, and a substantial proportion (37.8%) reported being novice in D&I research that focused on health equity. Participants reported high motivation (e.g., 62.8% were motivated to apply theories, models, frameworks for promoting health equity in D&I research), but low capability to conduct equity-oriented D&I research (e.g., 5% had the information needed for promoting health equity in D&I research). Most participants (62.2%) reported not having used measures to examine equity in their D&I projects, and for those who did use measures, they mainly used individual-level measures (vs. organizational- or structural-level measures). When asked about factors that could influence their ability to conduct equity-oriented D&I research, 44.4% reported not having the skills necessary, and 32.2% stated difficulties in receiving funding for equity-oriented D&I research. CONCLUSIONS: Study findings provide empirical insight into the perspectives of researchers from different backgrounds on what is needed to conduct equity-oriented D&I research. These data suggest the need for a multi-pronged approach to enhance the capability and opportunities for conducting equity-oriented D&I work, such as: training specifically in equity-oriented D&I, collaboration between D&I researchers with individuals with expertise and lived experience with health equity research, funding for equity-oriented D&I research, and recognition of the value of community engaged research in promotion packages.


Assuntos
Equidade em Saúde , Motivação , Estudos Transversais , Atenção à Saúde , Feminino , Humanos , Masculino , Pesquisadores
5.
BMC Public Health ; 21(1): 1945, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702247

RESUMO

BACKGROUND: Informal caregiving is an integral part of post-stroke recovery with strenuous caregiving demands often resulting in caregiving burden, threatening sustainability of caregiving and potentially impacting stroke survivor's outcomes. Our study aimed to examine and quantify objective and subjective informal care burden after stroke; and to explore the factors associated with informal care burden in Singapore. METHODS: Stroke patients and their informal caregivers were recruited from all five tertiary hospitals in Singapore from December 2010 to September 2013. Informal care comprised of assistance provided by informal caregivers with any of the activities of daily living. Informal care burden was measured by patients' likelihood of requiring informal care, hours of informal care required, and informal caregivers' Zarit's Burden Score. We examined informal care burden at 3-months and 12-months post-stroke. Generalized linear regressions were applied with control variables including patients' and informal caregivers' demographic characteristics, arrangement of informal care, and patients' health status including stroke severity (measured using National Institute of Health Stroke Scale), functional status (measured using Modified Rankin Scale), self-reported depression, and common comorbidities. RESULTS: Three hundred and five patients and 263 patients were examined at 3-months and 12-months. Around 35% were female and 60% were Chinese. Sixty three percent and 49% of the patients required informal care at 3-months and 12-months point, respectively. Among those who required informal care, average hours required per week were 64.3 h at 3-months and 76.6 h at 12-months point. Patients with higher functional dependency were more likely to require informal care at both time points, and required more hours of informal care at 3-months point. Female informal caregivers and those caring for patients with higher functional dependency reported higher Zarit's Burden. While informal caregivers who worked full-time reported higher burden, those caring for married stroke patients reported lower burden at 3-months point. Informal caregivers who co-cared with foreign domestic workers, i.e.: stay-in migrant female waged domestic workers, reported lower burden. CONCLUSIONS: Informal care burden remains high up to 12-months post-stroke. Factors such as functional dependency, stroke severity, informal caregiver gender and co-caring with foreign domestic workers were associated with informal care burden.


Assuntos
Atividades Cotidianas , Acidente Vascular Cerebral , Cuidadores , Efeitos Psicossociais da Doença , Feminino , Humanos , Assistência ao Paciente , Qualidade de Vida , Acidente Vascular Cerebral/terapia , Sobreviventes
6.
Implement Sci Commun ; 2(1): 61, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090524

RESUMO

BACKGROUND: Due to striking disparities in the implementation of healthcare innovations, it is imperative that researchers and practitioners can meaningfully use implementation determinant frameworks to understand why disparities exist in access, receipt, use, quality, or outcomes of healthcare. Our prior work documented and piloted the first published adaptation of an existing implementation determinant framework with health equity domains to create the Health Equity Implementation Framework. We recommended integrating these three health equity domains to existing implementation determinant frameworks: (1) culturally relevant factors of recipients, (2) clinical encounter or patient-provider interaction, and (3) societal context (including but not limited to social determinants of health). This framework was developed for healthcare and clinical practice settings. Some implementation teams have begun using the Health Equity Implementation Framework in their evaluations and asked for more guidance. METHODS: We completed a consensus process with our authorship team to clarify steps to incorporate a health equity lens into an implementation determinant framework. RESULTS: We describe steps to integrate health equity domains into implementation determinant frameworks for implementation research and practice. For each step, we compiled examples or practical tools to assist implementation researchers and practitioners in applying those steps. For each domain, we compiled definitions with supporting literature, showcased an illustrative example, and suggested sample quantitative and qualitative measures. CONCLUSION: Incorporating health equity domains within implementation determinant frameworks may optimize the scientific yield and equity of implementation efforts by assessing and ideally addressing implementation and equity barriers simultaneously. These practical guidance and tools provided can assist implementation researchers and practitioners to concretely capture and understand barriers and facilitators to implementation disparities.

7.
BMC Health Serv Res ; 18(1): 881, 2018 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-30466417

RESUMO

BACKGROUND: It is essential to study post-stroke healthcare utilization trajectories from a stroke patient caregiver dyadic perspective to improve healthcare delivery, practices and eventually improve long-term outcomes for stroke patients. However, literature addressing this area is currently limited. Addressing this gap, our study described the trajectory of healthcare service utilization by stroke patients and associated costs over 1-year post-stroke and examined the association with caregiver identity and clinical stroke factors. METHODS: Patient and caregiver variables were obtained from a prospective cohort, while healthcare data was obtained from the national claims database. Generalized estimating equation approach was used to get the population average estimates of healthcare utilization and cost trend across 4 quarters post-stroke. RESULTS: Five hundred ninety-two stroke patient and caregiver dyads were available for current analysis. The highest utilization occurred in the first quarter post-stroke across all service types and decreased with time. The incidence rate ratio (IRR) of hospitalization decreased by 51, 40, 11 and 1% for patients having spouse, sibling, child and others as caregivers respectively when compared with not having a caregiver (p = 0.017). Disability level modified the specialist outpatient clinic usage trajectory with increasing difference between mildly and severely disabled sub-groups across quarters. Stroke type and severity modified the primary care cost trajectory with expected cost estimates differing across second to fourth quarters for moderately-severe ischemic (IRR: 1.67, 1.74, 1.64; p = 0.003), moderately-severe non-ischemic (IRR: 1.61, 3.15, 2.44; p = 0.001) and severe non-ischemic (IRR: 2.18, 4.92, 4.77; p = 0.032) subgroups respectively, compared to first quarter. CONCLUSION: Highlighting the quarterly variations, we reported distinct utilization trajectories across subgroups based on clinical characteristics. Caregiver availability reducing hospitalization supports revisiting caregiver's role as potential hidden workforce, incentivizing their efforts by designing socially inclusive bundled payment models for post-acute stroke care and adopting family-centered clinical care practices.


Assuntos
Cuidadores/economia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Instituições de Assistência Ambulatorial/economia , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Cuidadores/estatística & dados numéricos , Bases de Dados Factuais , Pessoas com Deficiência/estatística & dados numéricos , Utilização de Instalações e Serviços , Medicina de Família e Comunidade/economia , Medicina de Família e Comunidade/estatística & dados numéricos , Feminino , Gastos em Saúde , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde/economia , Atenção Primária à Saúde/estatística & dados numéricos , Estudos Prospectivos , Cônjuges/estatística & dados numéricos , Acidente Vascular Cerebral/economia , Cuidados Semi-Intensivos/economia , Cuidados Semi-Intensivos/estatística & dados numéricos
8.
Perit Dial Int ; 37(3): 307-313, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27935536

RESUMO

♦ BACKGROUND: Peritoneal dialysis (PD) is challenging for patients with functional limitations, and assisted PD can support these patients, but previous reports of assisted PD have not examined the role of temporary assisted PD and had difficulty identifying adequate comparator cohorts. ♦ METHODS: Peritoneal Dialysis Assist (PDA), a 12-month pilot of long-term and temporary assisted PD was completed in multiple PD centers in British Columbia, Canada. Continuous cycler PD (CCPD) patients were identified for PDA by standardized criteria, and service could be long-term or temporary/respite. The PDA program provided daily assistance with cycler dismantle and setup, but patients remained responsible for cycler connections and treatment decisions. Outcomes were compared against both the general CCPD population and patients who met PDA criteria but were not enrolled (PDA-eligible). ♦ RESULTS: Fifty-three PDA patients had an 88% 1-year death- and transplant-censored technique survival that was similar to the general CCPD cohort (84%) and PDA-eligible cohort (86%). The PDA cohort had lower peritonitis rates (0.18 episodes/patient-year vs 0.22 and 0.36, respectively), but higher hospitalization (55% vs 34% and 35%, respectively). Long-term PDA cost approximately CDN$15,000/year in addition to existing dialysis costs. A total of 8/11 respite PDA patients (73%) returned to self-care PD after a median PDA use of 29 days, which costs $1,250/patient. ♦ CONCLUSIONS: Peritoneal Dialysis Assist provides effective support to functionally-limited CCPD patients and yields acceptable clinical outcomes. The program costs less than transfer to HD or long-term care, which represents cost minimization for failing self-care PD patients. Respite PDA provides effective temporary support; most patients returned to self-care PD and service was cost-effective compared with alternatives of hospitalization or transfer to HD.


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Autocuidado/métodos , Idoso , Colúmbia Britânica/epidemiologia , Análise Custo-Benefício , Feminino , Seguimentos , Hospitalização/tendências , Humanos , Falência Renal Crônica/economia , Falência Renal Crônica/mortalidade , Masculino , Projetos Piloto , Taxa de Sobrevida/tendências , Fatores de Tempo
9.
Front Plant Sci ; 7: 771, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27446094

RESUMO

Oil palm (Elaeis guineensis) is the most productive oil bearing crop worldwide. It has three fruit forms, namely dura (thick-shelled), pisifera (shell-less) and tenera (thin-shelled), which are controlled by the SHELL gene. The fruit forms exhibit monogenic co-dominant inheritance, where tenera is a hybrid obtained by crossing maternal dura and paternal pisifera palms. Commercial palm oil production is based on planting thin-shelled tenera palms, which typically yield 30% more oil than dura palms, while pisifera palms are female-sterile and have little to no palm oil yield. It is clear that tenera hybrids produce more oil than either parent due to single gene heterosis. The unintentional planting of dura or pisifera palms reduces overall yield and impacts land utilization that would otherwise be devoted to more productive tenera palms. Here, we identify three additional novel mutant alleles of the SHELL gene, which encode a type II MADS-box transcription factor, and determine oil yield via control of shell fruit form phenotype in a manner similar to two previously identified mutant SHELL alleles. Assays encompassing all five mutations account for all dura and pisifera palms analyzed. By assaying for these variants in 10,224 mature palms or seedlings, we report the first large scale accurate genotype-based determination of the fruit forms in independent oil palm planting sites and in the nurseries that supply them throughout Malaysia. The measured non-tenera contamination rate (10.9% overall on a weighted average basis) underscores the importance of SHELL genetic testing of seedlings prior to planting in production fields. By eliminating non-tenera contamination, comprehensive SHELL genetic testing can improve sustainability by increasing yield on existing planted lands. In addition, economic modeling demonstrates that SHELL gene testing will confer substantial annual economic gains to the oil palm industry, to Malaysian gross national income and to Malaysian government tax receipts.

10.
Methods Mol Biol ; 682: 279-89, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21057935

RESUMO

The ability to non-invasively assess DNA oxidation and its repair, has significant utility in large-scale, population-based studies. Such studies could include the assessments of: the efficacy of antioxidant intervention strategies, pathological roles of DNA oxidation in various disease states and population or interindividual differences in antioxidant defence and DNA repair. The most popular method, to non-invasively assess oxidative insult to the genome is by the analysis of urine for 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), using chromatographic techniques or immunoassay procedures. The provenance of extracellular 8-oxodG remains a subject for debate. However, previous studies have shown that factors, such as diet and cell death, do not appear to contribute to extracellular 8-oxodG, leaving processes, such as the repair of DNA and/or the 2'-deoxyribonucleotide pool, as the sole source of endogenous 8-oxodG. The method in this chapter describes a non-invasive approach for assessing oxidative stress, via the efficient extraction of urinary 8-oxodG using a validated solid-phase extraction procedure. Subsequent analysis by liquid chromatography-tandem mass spectrometry provides the advantages of sensitivity, internal standardisation, and robust peak identification, and is widely considered to be the "gold standard".


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dano ao DNA , Desoxiguanosina/análogos & derivados , Estresse Oxidativo , Espectrometria de Massas em Tandem/métodos , 8-Hidroxi-2'-Desoxiguanosina , Creatinina/urina , Desoxiguanosina/química , Desoxiguanosina/isolamento & purificação , Desoxiguanosina/urina , Humanos , Espectrometria de Massas , Isótopos de Nitrogênio , Extração em Fase Sólida
11.
Rapid Commun Mass Spectrom ; 24(16): 2329-40, 2010 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-20658679

RESUMO

Human exposure to polycyclic aromatic hydrocarbons (PAHs) from sources such as industrial or urban air pollution, tobacco smoke and cooked food is not confined to a single compound, but instead to mixtures of different PAHs. The interaction of different PAHs may lead to additive, synergistic or antagonistic effects in terms of DNA adduct formation and carcinogenic activity resulting from changes in metabolic activation to reactive intermediates and DNA repair. The development of a targeted DNA adductomic approach using liquid chromatography/tandem mass spectrometry (LC/MS/MS) incorporating software-based peak picking and integration for the assessment of exposure to mixtures of PAHs is described. For method development PAH-modified DNA samples were obtained by reaction of the anti-dihydrodiol epoxide metabolites of benzo[a]pyrene, benzo[b]fluoranthene, dibenzo[a,l]pyrene (DB[a,l]P) and dibenz[a,h]anthracene with calf thymus DNA in vitro and enzymatically hydrolysed to 2'-deoxynucleosides. Positive LC/electrospray ionisation (ESI)-MS/MS collision-induced dissociation product ion spectra data showed that the majority of adducts displayed a common fragmentation for the neutral loss of 116 u (2'-deoxyribose) resulting in a major product ion derived from the adducted base. The exception was the DB[a,l]P dihydrodiol epoxide adduct of 2'-deoxyadenosine which resulted in major product ions derived from the PAH moiety being detected. Specific detection of mixtures of PAH-adducted 2'-deoxynucleosides was achieved using online column-switching LC/MS/MS in conjunction with selected reaction monitoring (SRM) of the [M+H](+) to [M+H-116](+) transition plus product ions derived from the PAH moiety for improved sensitivity of detection and a comparison was made to detection by constant neutral loss scanning. In conclusion, different PAH DNA adducts were detected by employing SRM [M+H-116](+) transitions or constant neutral loss scanning. However, for improved sensitivity of detection optimised SRM transitions relating to the PAH moiety product ions are required for certain PAH DNA adducts for the development of targeted DNA adductomic methods.


Assuntos
Cromatografia Líquida/métodos , Adutos de DNA/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Espectrometria de Massas em Tandem/métodos , Animais , Bovinos , Cromatografia Líquida/instrumentação , DNA/química , Espectrometria de Massas em Tandem/instrumentação
12.
Indian J Surg Oncol ; 1(4): 294-302, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22693381

RESUMO

To assess the quality of high dose rate (H,D,R.) interstitial implants in breast cancer by using different volumetric indices and correlating them with skin and subcutaneous tissue toxicity. Out of 15 patients who were selected for interstitial implants after undergoing breast conservation surgery, five were treated radically with 34 Gy in 10 fractions in 5 days @ 3.4 Gy # twice daily and 10 patients recieved boost dose of 12 Gy in 4 fractions @ 3 Gy /# twice daily. The median follow up was 15 months. During each follow up assessment of late skin and subcutaneous tissue toxicity as per RTOG criteria was done . Various dosimetric indices were analysed. Dose Volume Histogram for dose per unit volume of skin for 10cc,5cc,2cc,1cc,0.1cc and 0.01cc was calculated. Best estimates and correlation of toxicity was revealed by assessment of Dose Nonuniformity Ratio(DNR) which also correlated well with geometry defining indices like Uniformity Index (UI).Volumetric assessment of skin dose for less than 2 cc correlated most with toxicity. DNR and UI can help us to assess and correlate late skin and subcutaneous tissue toxicity and thus serve useful to determine the quality of implant.

13.
Eur Urol ; 46(1): 28-41; discussion 41, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15183545

RESUMO

Pathological nomograms have allowed urologists to make accurate predictions about the behaviour of localized prostate cancers. However, predicting overall outcome and survival is not solely dependent on tumour characteristics; comorbidity is also a vital determinant of outcome The majority of prostate cancers are diagnosed in men over 65 years of age and many will have significant competing comorbid disease that will need to be accounted when considering eligibility for radical treatment. Most urologists currently make an educated guess about the risk posed by comorbid disease. Such an approach has the potential to allow personal bias to influence what should be an objective measure. This review describes the available methods for objectively assessing comorbid risk and assesses their potential utility to men with localized prostate cancer being considered for radical treatment.


Assuntos
Neoplasias da Próstata/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Comorbidade , Humanos , Masculino , Neoplasias da Próstata/complicações , Medição de Risco
14.
Rapid Commun Mass Spectrom ; 17(2): 126-34, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12512091

RESUMO

The analysis of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) represents an important biomarker of oxidative stress. A sensitive method for the detection of 8-oxodG in DNA samples has been developed that utilizes immunoaffinity column purification of 8-oxodG followed by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS) multiple reaction monitoring (MRM) mode analysis. An internal standard of stable-isotopically labelled 8-oxodG containing [(15)N(5)] was added prior to the enzymatic digestion of DNA to deoxynucleosides, which was then subjected to immunoaffinity column purification followed by microbore positive ion LC/MS/MS MRM. The 8-oxo-7,8-dihydroguanine (8-oxoG) base product ion at m/z 168 was monitored following cleavage of the glycosidic bond of the 8-oxodG [M+H](+) ion at m/z 284. Similar determinations were made for [(15)N(5)]8-oxodG by monitoring the [(15)N(5)]8-oxoG base product ion at m/z 173 formed from the [M+H](+) ion at m/z 289. The introduction of the immunoaffinity column purification step into the method represents a significant improvement for the accurate determination of 8-oxodG since all artefactual peaks that are observed following the direct injection of digested DNA onto the LC/MS/MS system are removed. The identity of these artefactual peaks has been confirmed to be 2'-deoxyguanosine (dG), thymidine (dT) and 2'-deoxyadenosine (dA). The presence of these artefactual peaks in MRM mode analysis can be explained as a consequence of a concentration effect due to their considerably higher relative abundance in DNA compared to 8-oxodG. The highest signal intensity was observed for the artefactual peak for dA due to the fact that the adenine base formed an adduct with methanol, which is a constituent of the mobile phase. The resulting [M+H](+) ion at m/z 284 (dA m/z 252 + CH(3)OH m/z 32) gave rise to a product ion at m/z 168 following the loss of deoxyribose in MRM mode analysis. Control calf thymus DNA was digested to deoxynucleosides and unmodfied deoxynucleosides were removed by immunoaffinity column purification; the enriched 8-oxodG was determined by LC/MS/MS MRM. The level of 8-oxodG in control calf thymus DNA was determined to be 28.8 +/- 1.2 8-oxodG per 10(6) unmodified nucleotides (n = 5) using 5 microg of digested DNA. The limit of detection of the microbore LC/MS/MS MRM for 8-oxodG was determined to be 25 fmol on-column with a signal-to-noise ratio of 3.5.


Assuntos
Cromatografia de Afinidade/métodos , Cromatografia Líquida/métodos , DNA/química , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Espectrometria de Massas/métodos , 8-Hidroxi-2'-Desoxiguanosina , Calibragem , Desoxiguanosina/imunologia , Azul de Metileno , Estrutura Molecular , Padrões de Referência
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