RESUMO
To ensure genomic medicine is delivered safely and effectively, it is crucial that healthcare professionals are able to understand and communicate genomic results. This Education Innovation describes a nationally agreed, cross-professional competency framework outlining the knowledge, skills and behaviors required to communicate genomic results. Using principles of the nominal group technique, consensus meetings with clinical, scientific and educational experts identified six stages in the return of results process, drafted and iterated competencies. Competencies were then mapped across three levels to acknowledge different degrees of experiences and scopes of practice. The framework was open for consultation with healthcare professionals and patient communities before being published. The finalized framework includes six core competency statements required to communicate genomic results. This framework is designed to be a guide for best practice and a developmental tool to support individuals and organizations. It can be used by healthcare professionals, such as genetic counselors, to identify individual learning needs or to structure the development of training for other healthcare professionals who are increasingly involved in requesting and returning results for genomic tests.
Assuntos
Conselheiros , Genômica , Humanos , Escolaridade , Pessoal de Saúde , ConhecimentoRESUMO
PURPOSE: The study aimed to develop a nationally agreed, cross-professional competency framework outlining the knowledge, skills, and behaviors required to facilitate genomic tests. METHODS: Using principles of the nominal group technique, a consensus meeting with 25 experts mapped themes to an initial framework and voted on areas of inconsistency. A revised framework was open for consultation with health care professionals and patient communities before being published. An evaluation, using an online survey, was conducted to explore early use and factors to facilitate adoption of the framework. RESULTS: The framework identified 8 competencies required to facilitate genomic tests. The evaluation (239 survey responses from health care professionals) indicated that the framework addresses a timely need among users and identified ways to improve awareness and accessibility for different health care professional groups. CONCLUSION: This framework can be used as a guide for best practice by health care professionals who request genomic tests. It can also provide a foundation to identify learning needs and structure training such that conversations about genomic testing can be delivered in a consistent manner across specialties. These competencies can also be used as a reference to evaluate how consent is facilitated in different specialty areas to enhance the responsible delivery of genomic medicine.
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Pessoal de Saúde , Aprendizagem , Competência Clínica , Consenso , Testes Genéticos , Pessoal de Saúde/educação , Humanos , Inquéritos e QuestionáriosRESUMO
PURPOSE: Widespread, quality genomics education for health professionals is required to create a competent genomic workforce. A lack of standards for reporting genomics education and evaluation limits the evidence base for replication and comparison. We therefore undertook a consensus process to develop a recommended minimum set of information to support consistent reporting of design, development, delivery, and evaluation of genomics education interventions. METHODS: Draft standards were derived from literature (25 items from 21 publications). Thirty-six international experts were purposively recruited for three rounds of a modified Delphi process to reach consensus on relevance, clarity, comprehensiveness, utility, and design. RESULTS: The final standards include 18 items relating to development and delivery of genomics education interventions, 12 relating to evaluation, and 1 on stakeholder engagement. CONCLUSION: These Reporting Item Standards for Education and its Evaluation in Genomics (RISE2 Genomics) are intended to be widely applicable across settings and health professions. Their use by those involved in reporting genomics education interventions and evaluation, as well as adoption by journals and policy makers as the expected standard, will support greater transparency, consistency, and comprehensiveness of reporting. Consequently, the genomics education evidence base will be more robust, enabling high-quality education and evaluation across diverse settings.
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Genômica , Relatório de Pesquisa , Consenso , Técnica Delphi , Humanos , Participação dos InteressadosRESUMO
Many genetic counselors will, at some point in their career, work alongside policy makers either at a local, regional, or national level. This commentary reflects my personal experience of working with policy makers in the National Health Service (NHS) in England. It outlines the challenges I faced and the lessons that I learnt along the way. This article is not meant to be a 'how to guide', rather to provide some practical tips to those new to working in policy and strategy. Throughout this commentary, I have compared working with policy makers with other areas that I have worked in, including genetic counseling, and shown how I have drawn on different skills to support this new area of my work. I hope that others will be able to reflect on my experience and see how they can also use their own attributes in similar situations.
Assuntos
Conselheiros , Aconselhamento Genético , Pessoal Administrativo , Inglaterra , Humanos , Medicina EstatalRESUMO
Application of viruses as a carrier, though not safe, to deliver genes to eye tissue was successful. However, a safer, nonviral, biocompatible lipid-based nanoparticle has never been tested to treat blinding eye diseases. We created an artificial virus using a nanoparticle, liposome-protamine-DNA complex (LPD), modified with a cell permeable peptide and a nuclear localization signaling (NLS) peptide, to deliver a functional gene for eye disease treatment. In the eye, a photochemical, 11-cis-retinal, allows the visual pigment rhodopsin to absorb light in the visible range. Without the photochemical, we lose the ability to see light. Retinal pigment epithelium protein 65 (Rpe65) is the key enzyme in regulating the availability of photochemical; deficiency of this gene results in a blinding eye disease. Here we show for the first time that LPD promotes efficient delivery in a cell specific-manner, and a long-term expression of Rpe65 gene to mice lacking Rpe65 gene, leading to in vivo correction of blindness. Thus, LPD nanoparticles could provide a promising, efficient, nonviral method of gene delivery with clinical applications in eye disease treatment.
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Cegueira/terapia , Terapia Genética/métodos , Nanomedicina/métodos , Nanopartículas/química , Visão Ocular/fisiologia , cis-trans-Isomerases/genética , Animais , Materiais Biocompatíveis/química , DNA/química , Técnicas de Transferência de Genes , Proteínas de Fluorescência Verde/metabolismo , Lipídeos/química , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Sinais de Localização Nuclear , Peptídeos/química , Fotoquímica , Protaminas/química , Retina/metabolismo , Epitélio Pigmentado da Retina/metabolismoRESUMO
Hematopoietic stem cells can be procured from unrelated donors via either the bone marrow (BM) aspiration or peripheral blood stem cell (PBSC) collection methods. There is no evidence from prospective randomized trials in the unrelated donor setting about the relative health-related quality-of-life (HRQoL) benefits/costs to donors. The goals of this prospective longitudinal investigation were to describe and compare the donation-related HRQoL experiences of 332 BM and PBSC donors. Donors were interviewed before donation, 48 hours after donation, weekly until fully recovered, and at 6 and 12 months after donation. Before donation, BM donors had lower confusion, fewer concerns, and were more prepared for donation. Shortly after donation, BM donors reported more physical side effects. BM donors also reported more donation-related impact on their social activities. However, BM donors reported somewhat better psychological status and were more likely to indicate that the donation made their lives more meaningful. There were virtually no longer term differences in the experiences of the 2 donor groups, including no recovery time difference beginning 3 weeks after donation. Although BM donors may experience the process as more physically stressful and more psychologically beneficial in the short term, the longer term HRQoL consequences of BM and PBSC donors are similar.
Assuntos
Transplante de Medula Óssea , Doadores Vivos/psicologia , Transplante de Células-Tronco de Sangue Periférico , Qualidade de Vida/psicologia , Doadores não Relacionados/psicologia , Adulto , Medula Óssea/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Classe Social , Coleta de Tecidos e ÓrgãosRESUMO
PURPOSE: Information on complementary and alternative medicine (CAM) use in Australian radiotherapy patients is sparse. This study investigated the type and prevalence of CAM amongst an Australian regional radiotherapy patient cohort and the disclosure of information to the consultant radiation oncologist. METHODS: A single hardcopy questionnaire survey was provided to patients regarding the use of CAM and discussion with the treating medical practitioner. The National Centre for Complementary and Alternative Medicine (NCCAM) classification was used to group responses. The study was open for a period of 4 months, and all patients on treatment during this period were approached. RESULTS: A total of 170 questionnaires were distributed to eligible patients, and 152 patients returned a completed questionnaire (89.4 % response rate). Sixty-nine of the 152 patients (45.4 %) reported active CAM use. Of the 69 patients who used CAM, mind-body medicine (n = 54, 78.3 %) and biological-based therapies (n = 54, 78.3 %) were the commonest NCCAM group, whilst manipulative/body-based therapies (n = 44, 63.8 %), whole medical systems (n = 7, 10.1 %) and energy therapies (n = 5, 7.2 %) were the least common. The most common therapies were vitamins and mineral supplementation (n = 33, 47.8 %) and massage therapy (n = 18, 26.1 %). Of note, only 29 participants stated that they had discussed CAM therapies with their radiation oncologist. CONCLUSIONS: CAM use was prevalent amongst cancer patients undergoing radiotherapy, but frequently not discussed with the treating radiation oncologist. Considering the high prevalence of CAM, further resources could be justifiably directed at providing this service for cancer patients to foster a more holistic approach to their care.
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Terapias Complementares/estatística & dados numéricos , Neoplasias/terapia , Adulto , Idoso , Austrália , Revelação/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/radioterapia , Radioterapia (Especialidade)/métodos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Few studies have examined the factors that predict information seeking by cancer patients. This study investigated the influence of different styles of adjustment to cancer, information goals and information needs on the information seeking by lung cancer patients. METHOD: Lung cancer patients were recruited at their first appointment with their radiation oncologist and completed two questionnaires, one month apart, containing the Patient Information Needs Questionnaire, Mini-Mental Adjustment to Cancer Scale, the number of information sources accessed and a purpose-built measure of cancer-related personal goals. RESULTS: Fifty-nine participants completed two questionnaires. The average number of information sources accessed by participants increased over the 1-month period, from 7.2 to 9.1 sources (p = 0.026). Information goals at time 1 predicted information seeking at time 2 (p = 0.014). Information needs at time 1 did not predict information seeking at time 2 (Disease Orientated information need p = 0.084, Action Orientated information need p = 0.229). Cognitive Avoidance at time 1 was negatively associated with the number of information sources accessed at time 2 (p = 0.046). This relationship became a non-significant trend (p = 0.066) when baseline information seeking was controlled for. No other adjustment style (at time 1) exhibited a significant relationship with information seeking at time 2. CONCLUSIONS: These findings suggest that information seeking may vary as a function of adjustment to cancer. Consequently, information provision to patients could be more appropriately tailored by attending to how a patient is adjusting to their diagnosis of cancer.
Assuntos
Adaptação Psicológica , Comportamento de Busca de Informação , Neoplasias Pulmonares/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 and 16mg/kg. Rats were killed 3h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity.
Assuntos
Testes de Carcinogenicidade , Furanos/toxicidade , Testes de Mutagenicidade , Animais , Medula Óssea/efeitos dos fármacos , Dano ao DNA , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Micronúcleos com Defeito Cromossômico , Ratos , Ratos Endogâmicos F344RESUMO
Titanium dioxide nanoparticles (TiO2-NPs) are being used increasingly for various industrial and consumer products, including cosmetics and sunscreens because of their photoactive properties. Therefore, the toxicity of TiO2-NPs needs to be thoroughly understood. In the present study, the genotoxicity of 10nm uncoated sphere TiO2-NPs with an anatase crystalline structure, which has been well characterized in a previous study, was assessed using the Salmonella reverse mutation assay (Ames test) and the single-cell gel electrophoresis (Comet) assay. For the Ames test, Salmonella strains TA102, TA100, TA1537, TA98 and TA1535 were preincubated with eight different concentrations of the TiO2-NPs for 4 h at 37 °C, ranging from 0 to 4915.2 µg per plate. No mutation induction was found. Analyses with transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS) showed that the TiO2-NPs were not able to enter the bacterial cell. For the Comet assay, TK6 cells were treated with 0-200 µg ml(-1) TiO2-NPs for 24 h at 37 °C to detect DNA damage. Although the TK6 cells did take up TiO2-NPs, no significant induction of DNA breakage or oxidative DNA damage was observed in the treated cells using the standard alkaline Comet assay and the endonuclease III (EndoIII) and human 8-hydroxyguanine DNA-glycosylase (hOGG1)-modified Comet assay, respectively. These results suggest that TiO2-NPs are not genotoxic under the conditions of the Ames test and Comet assay.
Assuntos
Ensaio Cometa/métodos , Dano ao DNA , Linfócitos/efeitos dos fármacos , Testes de Mutagenicidade , Nanopartículas/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Titânio/toxicidade , Linhagem Celular , Humanos , Microscopia Eletrônica de Transmissão , Espectrometria por Raios XRESUMO
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. Repeated dose inhalation toxicity data on NNK, particularly relevant to cigarette smoking, however, is surprisingly limited. Hence, there is a lack of direct information available on the carcinogenic and potential non-carcinogenic effects of NNK via inhalational route exposure. In the present study, the subchronic inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 23 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.2, 0.8, 3.2, or 7.8 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.0066, 0.026, 0.11, or 0.26 mg/L air) for 1 h/day for 90 consecutive days. Toxicity was evaluated by assessing body weights; food consumption; clinical pathology; histopathology; organ weights; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); tissue levels of the DNA adduct O6-methylguanine; blood and bone marrow micronucleus (MN) frequency; and bone marrow DNA strand breaks (comet assay). The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic lesions in the nose. Although the genotoxic biomarker O6-methylguanine was detected, genotoxicity from NNK exposure was negative in the MN and comet assays. The Lowest-Observed-Adverse-Effect-Level (LOAEL) was 0.8 mg/kg BW/day or 0.026 mg/L air of NNK for 1 h/day for both sexes. The No-Observed-Adverse-Effect-Level (NOAEL) was 0.2 mg/kg BW/day or 0.0066 mg/L air of NNK for 1 h/day for both sexes. The results of this study provide new information relevant to assessing the human exposure hazard of NNK.
Assuntos
Exposição por Inalação/efeitos adversos , Nicotiana/toxicidade , Nitrosaminas/toxicidade , Animais , Fumar Cigarros/efeitos adversos , Adutos de DNA/genética , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Masculino , Testes para Micronúcleos , Nível de Efeito Adverso não Observado , Nariz/efeitos dos fármacos , Nariz/patologia , Ratos , Ratos Sprague-Dawley , Fumaça/efeitos adversos , Nicotiana/químicaRESUMO
OBJECTIVE: This qualitative follow up of long-term (>5 years) cancer survivor and spouse participants from a large, previous study of quality of life after blood and marrow transplantation (BMT) was designed to gain a deeper understanding of lasting life changes they experienced. METHODS: Thirty spouse-survivor pairs, an average of 13 years post-BMT, were individually interviewed to identify lasting life changes. Participants were asked about their most significant long-lasting change since cancer/BMT, most significant positive change and negative change, and whether the experience had affected them and their spouse differently. RESULTS: Spouses and survivors spontaneously identified both positive and negative changes. Spouses reported a higher proportion of negative changes (24%) than did survivors (15%), and survivors a higher proportion of positive changes (85%) than spouses (76%). For both groups, the most frequent positive change was in 'perspective/outlook on life' and negative change was 'lingering health effects,' although survivors mentioned the latter twice as often as did spouses. Spouses were more likely to talk about changes in the first-person plural (we, us) that were largely emotional or in relation to the survivor, whereas survivors spoke of changes in the first-person singular (I, me) that occurred to them directly and were largely physical. CONCLUSIONS: Although both spouses and survivors described similar negative and positive long-lasting changes that continued an average of 13 years post-BMT, they reported differences in the ways they were impacted by the experience, which was reflected in the language they used. Implications for future studies, family education, and couples-based interventions are discussed.
Assuntos
Transplante de Medula Óssea/psicologia , Acontecimentos que Mudam a Vida , Neoplasias/psicologia , Cônjuges/psicologia , Sobreviventes/psicologia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
Nutritional manipulations early in life have been shown to influence growth rate and elicit long lasting effects which in turn has been found to impact lifespan. Therefore, we studied the long-term effects of pre-weaning dietary restriction implemented by litter expansion (4, 6, 8, 10, and 12 pups per dam: LS4, LS6, LS8, LS10, LS12) on male and female C57BL/6J mice. After weaning, these mice were fed ad libitum a commercial lab chow for the 15-month duration of the study. The male mice from large litter size (LS12) were significantly leaner and had reduced total fat mass compared to the normal size litters (LS 6) starting from weaning through to 15 months of age. Male LS10 & 12 mice also showed significant reduction in their fat depot masses at 15 months of age: gonadal, subcutaneous, and brown fat whereas the females did not mimic these findings. At 9 months of age, only male LS12 mice showed improved glucose tolerance and male LS12 mice also showed improved insulin tolerance starting at 5 months of age. In addition, we found that the male LS8, 10 & 12 mice at 15 months of age showed significantly reduced IGF-1 levels in the serum and various other organs (liver, gastrocnemius and brain cortex). Interestingly, the female LS8, 10, 12 mice showed a different pattern with reduced IGF-1 levels in serum, liver and gastrocnemius but not in the brain cortex. Similarly, the litter expanded mice showed sex specific response to levels of FGF21 and adiponectin with only the male mice showing increased FGF21 and adiponectin levels at 15 months of age. In summary, our data show that, litter expansion results in long-lasting metabolic changes that are age and sex dependent with the male mice showing an early and robust response compared to female mice.
Assuntos
Homeostase , Tamanho da Ninhada de Vivíparos , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , DesmameRESUMO
Dietary restriction (DR) was reported to either have no effect or reduce the lifespan of the majority of the 41-recombinant inbred (RI) lines studied by Liao et al. (Aging Cell, 2010, 9, 92). In an appropriately power longevity study (n > 30 mice/group), we measured the lifespan of the four RI lines (115-RI, 97-RI, 98-RI, and 107-RI) that were reported to have the greatest decrease in lifespan when fed 40% DR. DR increased the median lifespan of female RI-115, 97-RI, and 107-RI mice and male 115-RI mice. DR had little effect (<4%) on the median lifespan of female and male 98-RI mice and male 97-RI mice and reduced the lifespan of male 107-RI mice over 20%. While our study was unable to replicate the effect of DR on the lifespan of the RI mice (except male 107-RI mice) reported by Liao et al. (Aging Cell, 2010, 9, 92), we found that the genotype of a mouse had a major impact on the effect of DR on lifespan, with the effect of DR ranging from a 50% increase to a 22% decrease in median lifespan. No correlation was observed between the changes in either body composition or glucose tolerance induced by DR and the changes observed in lifespan of the four RI lines of male and female mice. These four RI lines of mice give the research community a unique resource where investigators for the first time can study the anti-aging mechanism of DR by comparing mice in which DR increases lifespan to mice where DR has either no effect or reduces lifespan.
Assuntos
Envelhecimento/genética , Dietoterapia/métodos , Genótipo , Longevidade/genética , Recombinação Genética , Animais , Composição Corporal , Feminino , Teste de Tolerância a Glucose , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos EndogâmicosRESUMO
The tobacco-specific nitrosamine NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] is found in tobacco products and tobacco smoke. NNK is a potent genotoxin and human lung carcinogen; however, there are limited inhalation data for the toxicokinetics (TK) and genotoxicity of NNK in vivo. In the present study, a single dose of 5 × 10-5, 5 × 10-3, 0.1, or 50 mg/kg body weight (BW) of NNK, 75% propylene glycol (vehicle control), or air (sham control) was administered to male Sprague-Dawley (SD) rats (9-10 weeks age) via nose-only inhalation (INH) exposure for 1 h. For comparison, the same doses of NNK were administered to male SD rats via intraperitoneal injection (IP) and oral gavage (PO). Plasma, urine, and tissue specimens were collected at designated time points and analyzed for levels of NNK and its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and tissue levels of DNA adduct O6-methylguanine by LC/MS/MS. TK data analysis was performed using a non-linear regression program. For the genotoxicity subgroup, tissues were collected at 3 h post-dosing for comet assay analysis. Overall, the TK data indicated that NNK was rapidly absorbed and metabolized extensively to NNAL after NNK administration via the three routes. The IP route had the greatest systemic exposure to NNK. NNK metabolism to NNAL appeared to be more efficient via INH than IP or PO. NNK induced significant increases in DNA damage in multiple tissues via the three routes. The results of this study provide new information and understanding of the TK and genotoxicity of NNK.
Assuntos
Nitrosaminas , Espectrometria de Massas em Tandem , Animais , Carcinógenos , Cromatografia Líquida de Alta Pressão , Dano ao DNA , Exposição por Inalação , Injeções Intraperitoneais , Masculino , Nitrosaminas/toxicidade , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , ToxicocinéticaRESUMO
4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. However, repeated inhalation toxicity data on NNK, which is more directly relevant to cigarette smoking, are currently limited. In the present study, the subacute inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 16 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.8, 3.2, 12.5, or 50 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.03, 0.11, 0.41, or 1.65 mg/L air) for 1 h/day for 14 consecutive days. Toxicity was evaluated by assessing body and organ weights; food consumption; clinical pathology; histopathology observations; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); O6-methylguanine DNA adduct formation; and blood and bone marrow micronucleus frequency. Whether the subacute inhalation toxicity of NNK followed Haber's Rule was also determined using additional animals exposed 4 h/day. The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic histopathological lesions in the nose. The lowest-observed-adverse-effect level (LOAEL) was 0.8 mg/kg BW/day or 0.03 mg/L air for 1 h/day for both sexes. An assessment of Haber's Rule indicated that 14-day inhalation exposure to the same dose at a lower concentration of NNK aerosol for a longer time (4 h daily) resulted in greater adverse effects than exposure to a higher concentration of NNK aerosol for a shorter time (1 h daily).
Assuntos
Nitrosaminas , Animais , Carcinógenos/toxicidade , Cromatografia Líquida de Alta Pressão , Feminino , Pulmão , Masculino , Nitrosaminas/toxicidade , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-DawleyRESUMO
Little is known about the health promotion, prevention, and disease screening behaviors of cancer survivors treated with hematopoietic cell transplantation (HCT), who undergo arduous treatment and may be at particular risk for late effects and secondary malignancies. The purposes of this study were to examine the current health and secondary prevention behaviors of long-term HCT survivors compared with matched controls without cancer, and to identify sociodemographic and clinical factors associated with appropriate preventive practices. HCT survivors (n = 662) were drawn from 40 North American transplantation centers. Peer-nominated acquaintances of survivors matched on sex, age, education, and marital status served as controls (n = 158). Data were collected a mean of 6.7 years post-HCT (range, 1.8-22.6 years). Despite a greater frequency of physical exams, the HCT survivors had similar health and screening behaviors as the matched controls. Sociodemographic factors were associated with health prevention behaviors in expected ways. Some differences between disease group and type of transplant were found, with survivors of acute leukemia less likely to report regular exercise, autologous transplant survivors more likely than allogeneic transplant survivors to report screenings for breast and cervical cancer, and allogeneic transplant survivors more likely than autologous transplant survivors to report undergoing a skin exam in the previous year. Despite higher levels of engagement with health care providers, HCT survivors had similar health behaviors as matched controls and comparable to those reported by cancer survivors who did not undergo HCT. There remains considerable room for improvement. These findings support the need for further education of both HCT survivors and health practitioners.
Assuntos
Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Transplante de Células-Tronco Hematopoéticas , Neoplasias/terapia , Serviços Preventivos de Saúde/estatística & dados numéricos , Sobreviventes/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Neoplasias/prevenção & controle , Segunda Neoplasia Primária/prevenção & controle , Exame Físico/estatística & dados numéricos , Prevenção Secundária , Inquéritos e Questionários , Fatores de Tempo , Adulto JovemRESUMO
Hematopoietic cell transplantation (HCT) is an intensive treatment for hematologic malignancies that has the potential to cure disease or prolong life, but also to impair quality of life for survivors. Earlier studies have suggested that various factors are associated with physical and mental health after HCT. In this study, we evaluated demographic and clinical factors before and after HCT and selected psychosocial factors after HCT, exploring their association with self-reported physical and mental health. We studied a cohort of 662 survivors at a median of 6.6 years after HCT. Pre-HCT demographic and clinical factors accounted for only a small amount of the variance in physical and mental health post-HCT (3% and 1%, respectively). Adding post-HCT clinical variables to the pre-HCT factors accounted for 32% and 7% of physical and mental outcomes, respectively. When both clinical and psychosocial factors were considered, better physical health post-HCT was associated with younger age, race other than white, higher current family income, currently working or being a student, less severe transplantation experience (ie, not experiencing graft-versus-host disease), fewer current comorbidities, higher Karnofsky status, less social constraint, less social support, and less trait anxiety. This multivariate model accounted for 36% of the variance in physical health, with the psychosocial variables contributing very little. When both clinical and psychosocial factors were considered, better mental health after HCT was associated with more severe transplantation experience, less social constraint, greater spiritual well being, and less trait anxiety. This multivariate model accounted for 56% of the variance in mental health, with the psychosocial factors accounting for most of the variance. These data suggest that clinical factors are explanatory for much of the post-HCT physical health reported by HCT survivors, but very little of self-perceived mental health. These observations provide insight into the identification of factors that can allow recognition of at-risk patients, as well as factors amenable to intervention.
Assuntos
Transplante de Células-Tronco Hematopoéticas/psicologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco , Autorrelato , Sobreviventes , Resultado do Tratamento , Adulto JovemRESUMO
Religiosity and spirituality have been associated with better survival in large epidemiologic studies. This study examined the relationship between spiritual absence and 1-year all-cause mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Depression and problematic compliance were examined as possible mediators of a significant spiritual absence-mortality relationship. Eighty-five adults (mean = 46.85 years old, SD = 11.90 years) undergoing evaluation for allogeneic HSCT had routine psychologie evaluation prior to HSCT admission. The Millon Behavioral Medicine Diagnostic was used to assess spiritual absence, depression, and problematic compliance, the psychosocial predictors of interest. Patient status at 1 year and survival time in days were abstracted from medical records. Cox regression analysis was used to examine the relationship between the psychosocial factors of interest and mortality after adjusting for relevant biobehavioral factors. Twenty-nine percent (n = 25) of participants died within 1 year of HSCT. After covarying for disease type, individuals with the highest spiritual absence and problematic compliance scores were significantly more likely to die 1-year post-HSCT (hazard ratio [HR] = 2.49, P = .043 and HR = 3.74, P = .029, respectively), particularly secondary to infection, sepsis, or graft-versus-host disease (GVHD) (HR = 4.56, P = .01 and HR = 5.61, P = .014), relative to those without elevations on these scales. Depression was not associated with 1-year mortality, and problematic compliance did not mediate the relationship between spiritual absence and mortality. These preliminary results suggest that both spiritual absence and problematic compliance may be associated with poorer survival following HSCT. Future research should examine these relations in a larger sample using a more comprehensive assessment of spirituality.
Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Espiritualidade , Feminino , Comportamentos Relacionados com a Saúde , Transplante de Células-Tronco Hematopoéticas/psicologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Both obesity and low income are risk factors of asthma and their joint effect on the disease has not been studied previously. OBJECTIVE: To examine the influence of obesity and household income and their joint effect on asthma. METHODS: The authors conducted an analysis based on data from 115,722 subjects 18+ years of age who participated in a national survey in 2005. Logistic regression analysis was used to adjust for covariates. The joint effect of household income and body mass index (BMI) on asthma was assessed on an additive scale. RESULTS: Obesity associated with an increased risk of asthma was significant in all income categories in women but was only significant in the low-income group in men. A stronger association between obesity and asthma was observed in low- than in high-income families. For men and women combined, the adjusted odds ratio for those with a BMI value of 35 kg/m(2) or more versus those with a BMI less than 25 kg/m(2) was 2.01 in the low-household income group compared with only 1.47 in the high-income group. The corresponding adjusted relative excess risk of interaction was 1.50 (95% confidence interval [CI]: 0.88, 1.65) for men and women combined and was 2.73 (95% CI: 1.50, 5.39) for women. CONCLUSION: These data suggested an interactive effect of obesity and low-household income on the prevalence of asthma.