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BACKGROUND: Recent cohort studies suggested that serum levels of soluble Receptor for Advanced Glycation End-products (sRAGE) are associated with the risk of cardiovascular disease. We hypothesized that sRAGE levels are associated with subclinical atherosclerosis in a racially and ethnically diverse population. METHODS AND RESULTS: 828 stroke-free participants from the Northern Manhattan Study (mean age 71.1±8.7yrs; 64% Hispanic, 19% black, and 17% white) underwent high-resolution carotid B-mode ultrasound to measure carotid plaque (present in 62% of subjects) and intima-media thickness (IMT) (mean Total=0.96±0.10 mm). Serum sRAGE was measured by ELISA and associations tested between sRAGE with IMT and plaque presence. Soluble RAGE levels were not associated with plaque presence or IMT after adjusting for sociodemographic, vascular risk factors and medication use. Stratification by race-ethnicity did not reveal any associations with carotid IMT or plaque. CONCLUSION: In the present study, sRAGE levels were not associated with carotid atherosclerosis.
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Doenças das Artérias Carótidas/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Negro ou Afro-Americano , Biomarcadores/sangue , Doenças das Artérias Carótidas/diagnóstico , Doenças das Artérias Carótidas/etnologia , Espessura Intima-Media Carotídea , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Hispânico ou Latino , Humanos , Masculino , Cidade de Nova Iorque/epidemiologia , Placa Aterosclerótica , Fatores de Risco , População BrancaRESUMO
A porcine deep partial-thickness wound model was used to evaluate the effects of a newly developed topical aqueous oxygen emulsion (TOE) on wound repair. The wounds were treated with TOE, which contains super-saturated oxygen or vehicle control. Semiquantitative immunofluorescent staining was performed to examine protein production for type I and type III collagen and vascular endothelial growth factor (VEGF). Immunofluorescent staining revealed higher protein levels of type I and type III collagen and VEGF in the TOE treatment group. Histological analysis also revealed improved angiogenesis and granulation tissue formation with topical TOE treatment and was consistent with the protein expression. In addition, the histology examination demonstrated faster epithelialization in wounds treated with TOE. The study suggests that sustained high levels of oxygen released by TOE may promote the process of wound repair through increasing collagen deposition and angiogenesis as well as stimulating epithelialization.
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Colágeno/metabolismo , Emulsões/farmacologia , Epitélio/efeitos dos fármacos , Tecido de Granulação/efeitos dos fármacos , Neovascularização Fisiológica , Oxigênio/administração & dosagem , Oxigênio/química , Cicatrização/efeitos dos fármacos , Animais , Movimento Celular , Proliferação de Células , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Tecido de Granulação/metabolismo , Microscopia de Fluorescência , Morfogênese , Espécies Reativas de Oxigênio/metabolismo , Suínos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: We sought to identify high-risk areas of pancreatic cancer incidence, and determine if clusters of persons diagnosed with pancreatic cancer were more likely to be located near arsenic-contaminated drinking water wells. METHODS: A total of 5,707 arsenic samples were collected from December 2000 to May 2008 by the Florida Department of Health, representing more than 5,000 individual privately owned wells. During that period, 0.010 ppm (10 ppb) or greater arsenic levels in private well water were considered as the threshold based on standard of United States Environmental Protection Agency (EPA). Spatial modeling was applied to pancreatic cancer cases diagnosed between 1998-2002 in Florida (n = 11,405). Multivariable logistic regression was used to determine if sociodemographic indicators, smoking history, and proximity to arsenic-contaminated well sites were associated with residence at the time of pancreatic cancer diagnosis occurring within versus outside a cluster. RESULTS: Spatial modeling identified 16 clusters in which 22.6% of all pancreatic cancer cases were located. Cases living within 1 mile of known arsenic-contaminated wells were significantly more likely to be diagnosed within a cluster of pancreatic cancers relative to cases living more than 3 miles from known sites (odds ratio = 2.1 [95% CI = 1.9, 2.4]). CONCLUSIONS: Exposure to arsenic-contaminated drinking water wells may be associated with an increased risk of pancreatic cancer. However, case-control studies are needed in order to confirm the findings of this ecological analysis. These cluster areas may be appropriate to evaluate pancreatic cancer risk factors, and to perform targeted screening and prevention studies.
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Arsênio/toxicidade , Água Potável/análise , Exposição Ambiental/efeitos adversos , Neoplasias Pancreáticas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arsênio/análise , Análise por Conglomerados , Feminino , Florida/epidemiologia , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/induzido quimicamente , Abastecimento de Água/análise , Adulto JovemRESUMO
Defective DNA repair may contribute to early age and late stage at time of diagnosis and mutations in critical tumor suppressor genes, such as TP53 in breast cancer. Using DNA samples from 436 breast cancer cases (374 Caucasians and 62 African-Americans), we tested these associations with 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways: (i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) double-strand break repair: NBS1 E185Q and XRCC3 T241M; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A and MSH6 G39E and (iv) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q. Younger age at diagnosis (<50) was associated with ERCC2 312 DN/NN genotypes [odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.10, 2.81] and NBS1 185 QQ genotype (OR = 3.09; 95% CI = 1.47, 6.49). The XPC 939 QQ genotype was associated with TP53 mutations (OR = 5.80; 95% CI = 2.23, 15.09). There was a significant trend associating younger age at diagnosis (<50) with increasing numbers of risk genotypes for ERCC2 312 DN/NN, MSH6 39 EE and NBS1 185 QQ (P(trend) < 0.001). A similar significant trend was also observed associating TP53 mutations with increasing numbers of risk genotypes for XRCC1 399 QQ, XPC 939 QQ, ERCC4 415 QQ and XPC 499 AA (P(trend) < 0.001). Our pilot data suggest that nsSNPs of multiple DNA repair pathways are associated with younger age at diagnosis and TP53 mutations in breast cancer and larger studies are warranted to further evaluate these associations.
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Neoplasias da Mama/genética , Reparo do DNA , Genes p53 , Mutação , Polimorfismo Genético , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Proteína 1 Complementadora Cruzada de Reparo de Raio-XRESUMO
Human lactoferrin (hLF), a glycoprotein of the transferrin family, has recently been shown to stimulate wound repair through its antimicrobial effect and inflammation modulation. A recent study with several non-skin cell lines indicated that hLF may also have a stimulatory effect on cell proliferation. To explore the role of hLF in wound healing, we used recombinant human lactoferrin (holo-rhLF), derived from transgenic rice, to examine the effects of holo-rhLF on cell proliferation, migration, attachment, and survival in a human primary skin fibroblast culture system. This study revealed that holo-rhLF not only significantly stimulates fibroblast proliferation but also has synergistic effects with fibroblast growth factor-2 and antagonistic effects with transforming growth factor-beta1 on cell proliferation. Furthermore, using a chamber migration assay, our results demonstrate that holo-rhLF promotes fibroblast migration in a dosage-dependent manner. More importantly, holo-rhLF significantly increased cell viability and protected cells from death when they were stressed by either serum depletion or 12-O-tetradecanoylphorbol-13-acetate exposure. No significant effect was observed on cell attachment. In conclusion, these findings reveal the multiple functions of holo-rhLF in human skin fibroblasts and indicate its potential application in wound therapy by enhancing cell proliferation and migration as well as protecting cells from apoptosis.
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Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/fisiologia , Lactoferrina/farmacologia , Oryza/metabolismo , Proteínas Recombinantes/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Fator 2 de Crescimento de Fibroblastos/farmacologia , Flavonoides/farmacologia , Humanos , Marcação In Situ das Extremidades Cortadas , Lactoferrina/metabolismo , MAP Quinase Quinase Quinases/antagonistas & inibidores , Plantas Geneticamente Modificadas , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Non-Hodgkin's lymphoma (NHL) is a cancer closely associated with immune function, and the tumor necrosis factor (TNF) G-308A promoter polymorphism, which influences immune function and regulation, was recently reported by the InterLymph Consortium to be associated with NHL risk. TNF signaling activates the nuclear factor-kappaB (NF-kappaB) canonical pathway, leading to transcriptional activation of multiple genes that influence inflammation and immune response. We hypothesized that, in addition to TNF signaling, common genetic variation in genes from the NF-kappaB canonical pathway may affect risk of NHL. We genotyped 54 single nucleotide polymorphisms (SNP) within TNF, lymphotoxin A LTA, and nine NF-kappaB genes from the canonical pathway (TNFRSF1A, TRADD, TRAF2, TRAF5, RIPK1, CHUK, IKBKB, NFKB1, and REL) in a clinic-based study of 441 incident cases and 475 frequency-matched controls. Tagging SNPs were selected from HapMap supplemented by putative functional SNPs for LTA/TNF. We used principal components and haplo.stats to model gene-level associations and logistic regression to model SNP-level associations. Compared with the wild-type (GG), the AA genotype for the TNF promoter polymorphism G-308A (rs1800629) was associated with increased risk of NHL [odds ratio (OR), 2.14; 95% confidence interval (95% CI), 0.94-4.85], whereas the GA genotype was not (OR, 1.00; 95% CI, 0.74-1.34). This association was similar for follicular lymphoma and diffuse large B-cell lymphoma. A previously reported LTA/TNF haplotype was also associated with NHL risk. In gene-level analysis of the NF-kappaB pathway, only NFKB1 showed a statistically significant association with NHL (P = 0.049), and one NFKB1 tagSNP (rs4648022) was associated with NHL risk overall (ordinal OR, 0.59; 95% CI, 0.41-0.84; Ptrend = 0.0037) and for each of the common subtypes. In conclusion, we provide additional evidence for the role of genetic variation in TNF and LTA SNPs and haplotypes with risk of NHL and also provide some of the first preliminary evidence for an association of genetic variation in NFKB1, a downstream target of TNF signaling, with risk of NHL.
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Linfoma não Hodgkin/genética , Linfotoxina-alfa/genética , NF-kappa B/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Haplótipos , Humanos , Modelos Logísticos , Linfoma não Hodgkin/imunologia , Linfotoxina-alfa/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/imunologia , Risco , Transdução de Sinais , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Concerns regarding the safety of dietary trans-fatty acids (tFAs) have generated recent public interest, scientific discussion and legislative action. Although most widely recognized as a risk factor for cardiovascular disease, associations between tFA intake and incident cancer have also been proposed. With respect to colorectal cancer (CRC), existing observational data remain limited and inconclusive. Therefore, we conducted a prospective evaluation of tFA intake and CRC risk, overall and by anatomic subsite, among participants in the Iowa Women's Health Study (IWHS), a population-based cohort of older women (ages 55-69 years at enrollment). Exposure data were collected at baseline using a semiquantitative food-frequency questionnaire. Incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. CRC risks were estimated using Cox proportional hazards regression models. In total, 35,216 women met our inclusion criteria and 1,229 CRC cases (631 proximal, 571 distal, 27 site not specified) were observed through 18 years of follow-up. Adjusting for age and total energy consumption, tFA intake in the 4th versus 1st quartile was not significantly associated with overall CRC risk [relative risk (RR) = 1.12; 95% confidence interval (CI) = 0.96-1.32]. Similarly, risk estimates based on proximal (RR = 1.09; 95% CI = 0.87-1.37) and distal (RR = 1.18; 95% CI = 0.93-1.49) CRC subsites did not differ from unity. Multivariable adjustment yielded slightly attenuated risk estimates, but the observed associations were not meaningfully altered. Given these findings, tFA intake does not appear to be a major CRC risk factor, at least among older women.
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Neoplasias Colorretais/epidemiologia , Inquéritos Epidemiológicos , Ácidos Graxos trans/administração & dosagem , Ácidos Graxos trans/farmacologia , Idoso , Feminino , Humanos , Iowa/epidemiologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de RiscoRESUMO
Genetic variations in DNA repair may impact repair functions, DNA damage and breast cancer risk. Using data/samples collected from the first 752 Caucasians and 141 African-Americans in an ongoing case-control study, we examined the association between breast cancer risk and 18 non-synonymous single-nucleotide polymorphisms (nsSNPs) in four DNA repair pathways-(i) base excision repair: ADPRT V762A, APE1 D148E, XRCC1 R194W/R280H/R399Q and POLD1 R119H; (ii) nucleotide excision repair: ERCC2 D312N/K751Q, ERCC4 R415Q, ERCC5 D1104H and XPC A499V/K939Q; (iii) mismatch repair: MLH1 I219V, MSH3 R940Q/T1036A and MSH6 G39E and (iv) double-strand break repair: NBS1 E185Q and XRCC3 T241M. In Caucasians, breast cancer risk was significantly associated with ADPRT 762VV [odds ratio (OR) = 1.45; 95% confidence interval (CI) = 1.03, 2.03], APE1 148DD (OR = 1.44; 95% CI = 1.03, 2.00), MLH1 219II/IV (OR = 1.87; 95% CI = 1.11, 3.16) and ERCC4 415QQ (OR = 8.64; 95% CI = 1.04, 72.02) genotypes. With a limited sample size, we did not observe any significant association in African-Americans. However, there were significant trends in breast cancer risk with increasing numbers of risk genotypes for ADPRT 762VV, APE1 148DD, ERCC4 415RQ/QQ and MLH1 219II/IV (P(trend) < 0.001) in Caucasians and ADPRT 762VA, ERCC2 751KQ/QQ and NBS1 185EQ/QQ in African-Americans (P(trend) = 0.006), respectively. Our results suggest that combined nsSNPs in multiple DNA repair pathways may contribute to breast cancer risk and larger studies are warranted to further evaluate polygenic models of DNA repair in breast cancer risk.
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Neoplasias da Mama/genética , Reparo do DNA/genética , Modelos Genéticos , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Aberrant Wnt/beta-catenin signaling leading to nuclear accumulation of the oncogene product beta-catenin is observed in a wide spectrum of human malignancies. The destruction complex in the Wnt/beta-catenin pathway is critical for regulating the level of beta-catenin in the cytoplasm and in the nucleus. Here, we report a comprehensive study of the contribution of genetic variation in six genes encoding the beta-catenin destruction complex (APC, AXIN1, AXIN2, CSNK1D, CSNK1E, and GSK3B) to breast cancer using a Mayo Clinic Breast Cancer Case-Control Study. A total of 79 candidate functional and tagging single nucleotide polymorphisms (SNP) were genotyped in 798 invasive cases and 843 unaffected controls. Of these, rs454886 in the APC tumor suppressor gene was associated with increased breast cancer risk (per allele odds ratio, 1.23; 95% confidence intervals, 1.05-1.43; P(trend) = 0.01). In addition, five SNPs in AXIN2 were associated with increased risk of breast cancer (P(trend) < 0.05). Haplotype-based tests identified significant associations between specific haplotypes in APC and AXIN2 (P < or = 0.03) and breast cancer risk. Further characterization of the APC and AXIN2 variants suggested that AXIN2 rs4791171 was significantly associated with risk in premenopausal (P(trend) = 0.0002) but not in postmenopausal women. The combination of our findings and numerous genetic and functional studies showing that APC and AXIN2 perform crucial tumor suppressor functions suggest that further investigation of the contribution of AXIN2 and APC SNPs to breast cancer risk are needed.
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Neoplasias da Mama/genética , Variação Genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas/genética , beta Catenina/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Genótipo , Haplótipos , Humanos , Invasividade Neoplásica , RiscoRESUMO
Here we summarize the contributions to Group 13 of the Genetic Analysis Workshop 15 held in St. Pete Beach, Florida, on November 12-14, 2006. The focus of this group was to identify candidate genes associated with rheumatoid arthritis or surrogate outcomes. The association methods proposed in this group were diverse, from better known approaches, such as logistic regression for single nucleotide polymorphism (SNP) analysis and haplotype sharing tests to methods less familiar to genetic epidemiologists, such as machine learning and visualization methods. The majority of papers analyzed Genetic Analysis Workshop 15 Problems 2 (rheumatoid arthritis data) and 3 (simulated data). The highlighted points of this group analyses were: (1) haplotype-based statistics can be more powerful than single SNP analysis for risk-locus localization; (2) considering linkage disequilibrium block structure in haplotype analysis may reduce the likelihood of false-positive results; and (3) visual representation of genetic models for continuous covariates may help identify SNPs associated with the underlying quantitative trait loci.
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Artrite Reumatoide/genética , Epistasia Genética , Haplótipos , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Smaller-scale evaluations suggest that common genetic variation in candidate genes related to immune function may predispose to the development of non-Hodgkin lymphoma (NHL). We report an analysis of variants within genes associated with immunity and inflammation and risk of NHL using a panel of 9412 single-nucleotide polymorphisms (SNPs) from 1253 genes in a study of 458 patients with NHL and 484 frequency-matched controls. We modeled haplotypes and risk of NHL, as well as the main effects for all independent SNPs from a gene in multivariate logistic regression models; we separately report results for nonsynonymous (ns) SNPs. In gene-level analyses, the strongest findings (P < or = .001) were for CREB1, FGG, MAP3K5, RIPK3, LSP1, TRAF1, DUSP2, and ITGB3. In nsSNP analyses, the strongest findings (P < or = .01) were for ITGB3 L59P (odds ratio [OR] = 0.66; 95% confidence interval [CI] 0.52-0.85), TLR6 V427A (OR = 5.20; CI 1.77-15.3), SELPLG M264V (OR = 3.20; CI 1.48-6.91), UNC84B G671S (OR = 1.50; CI 1.12-2.00), B3GNT3 H328R (OR = 0.74; CI 0.59-0.93), and BAT2 V1883L (OR = 0.64; CI 0.45-0.90). Our results suggest that genetic variation in genes associated with immune response (TRAF1, RIPK3, BAT2, and TLR6), mitogen-activated protein kinase (MAPK) signaling (MAP3K5, DUSP2, and CREB1), lymphocyte trafficking and migration (B3GNT3, SELPLG, and LSP1), and coagulation pathways (FGG and ITGB3) may be important in the etiology of NHL, and should be prioritized in replication studies.
Assuntos
Variação Genética/genética , Imunidade/genética , Inflamação/genética , Linfoma não Hodgkin/genética , Estudos de Casos e Controles , Genes Neoplásicos , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Modelos Logísticos , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/etiologia , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
The nuclear factor-kappaB (NF-kappaB) family of transcription factors regulates the expression of a variety of genes involved in apoptosis and immune response. We examined relationships between genotypes at five NF-kappaB subunits (NFKB1, NFKB2, REL, RELA, and RELB) and variable expression levels of 15 NF-kappaB regulated proteins with heritability greater than 0.40: BCL2A1, BIRC2, CD40, CD44, CD80, CFLAR, CR2, FAS, ICAM1, IL15, IRF1, JUNB, MYC, SLC2A5, and VCAM1. SNP genotypes and expression phenotypes from pedigrees of Utah residents with ancestry from northern and western Europe were provided by Genetic Analysis Workshop 15 and supplemented with additional genotype data from the International HapMap Consortium. We conducted association, linkage, and family-based association analyses between each candidate gene and the 15 heritable expression phenotypes. We observed consistent results in association and linkage analyses of the NFKB1 region (encoding p50) and levels of FAS and IRF1 expression. FAS is a cell surface protein that also belongs to the TNF-receptor family; signals through FAS are able to induce apoptosis. IRF1 is a member of the interferon regulatory transcription factor family, which has been shown to regulate apoptosis and tumor-suppression. Analyses in the REL region (encoding c-Rel) revealed linkage and association with CD40 phenotype. CD40 proteins belong to the tumor necrosis factor (TNF)-receptor family, which mediates a broad variety of immune and inflammatory responses. We conclude that variation in the genes encoding p50 and c-Rel may play a role in NF-kappaB-related transcription of FAS, IRF1, and CD40.
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The goal of this paper is to investigate the effects of normalization procedures for expression data on linkage results. We selected the two most commonly used expression data extraction and normalization methods, Affymetrix global scaling and dChip invariant. After applying these two methods in 3554 expression phenotypes, we identified 45 phenotypes that were more likely to be genetic for either normalization procedure. A genome-wide linkage scan was performed on these expression values (45 phenotypes x 2 normalizations) using 2272 SNPs. Our results showed that: 1) the dChip normalization might inflate the LOD scores because the dChip normalization yielded LOD scores > 3.0 30% more frequently than the Affy normalization, and 2) the difference in LODs between the normalizations were not correlated with their heritabilities. In summary, we conclude, as have other published reports, that normalization methods play an important role in the linkage results, and that some significant linkage signals might be due to a specific normalization method.
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The goal of this paper is to investigate the effect of using principal components as a data reduction method for expression data in linkage analysis. We used 45 probes normalized using the Affymetrix Global Scaling that had evidence of high heritability to estimate the first 10 principal components (PC). A genome-wide linkage scan was performed on the 45 expression values and the 10 PCs using 2272 single-nucleotide polymorphisms. Our conclusions were: 1) PC analyses under-performed the single-probe analysis for known signals; 2) the PC that best reproduced the single-probe analysis was primarily composed of that probe; 3) no new signals were detected in the PC analysis; 4) no new pleiotropic effects were detected in the PC analysis.
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CONTEXT: Although olanzapine has been widely adopted as a treatment of choice for schizophrenia, its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a standard antipsychotic drug. OBJECTIVE: To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia. DESIGN AND SETTING: Double-blind, randomized controlled trial with randomization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers. PARTICIPANTS: Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia or schizoaffective disorder, serious symptoms, and serious dysfunction for the previous 2 years. Fifty-nine percent fully completed and 36% partially completed follow-up assessments. INTERVENTIONS: Patients were randomly assigned to receive flexibly dosed olanzapine, 5 to 20 mg/d, with prophylactic benztropine, 1 to 4 mg/d (n = 159); or haloperidol, 5 to 20 mg/d (n = 150), for 12 months. MAIN OUTCOME MEASURES: Standardized measures of symptoms, quality of life, neurocognitive status, and adverse effects of medication. Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole (ie, consumption of all resources on behalf of these patients). RESULTS: There were no significant differences between groups in study retention; positive, negative, or total symptoms of schizophrenia; quality of life; or extrapyramidal symptoms. Olanzapine was associated with reduced akathisia in the intention-to-treat analysis (P<.001) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug. Small but significant advantages were also observed on measures of memory and motor function. Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs, ranging from 3000 dollars to 9000 dollars annually. Differences in societal costs were somewhat smaller and were not significant. CONCLUSION: Olanzapine does not demonstrate advantages compared with haloperidol (in combination with prophylactic benztropine) in compliance, symptoms, extrapyramidal symptoms, or overall quality of life, and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost.
Assuntos
Antipsicóticos/economia , Antipsicóticos/uso terapêutico , Haloperidol/economia , Haloperidol/uso terapêutico , Pirenzepina/análogos & derivados , Pirenzepina/economia , Pirenzepina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/economia , Adulto , Acatisia Induzida por Medicamentos , Antipsicóticos/efeitos adversos , Benzodiazepinas , Benzotropina/uso terapêutico , Método Duplo-Cego , Feminino , Haloperidol/efeitos adversos , Custos de Cuidados de Saúde , Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/uso terapêutico , Testes Neuropsicológicos , Olanzapina , Pirenzepina/efeitos adversos , Qualidade de Vida , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Supported housing, integrating clinical and housing services, is a widely advocated intervention for homeless people with mental illness. In 1992, the US Department of Housing and Urban Development (HUD) and the US Department of Veterans Affairs (VA) established the HUD-VA Supported Housing (HUD-VASH) program. METHODS: Homeless veterans with psychiatric and/or substance abuse disorders or both (N = 460) were randomly assigned to 1 of 3 groups: (1) HUD-VASH, with Section 8 vouchers (rent subsidies) and intensive case management (n = 182); (2) case management only, without special access to Section 8 vouchers (n = 90); and (3) standard VA care (n = 188) Primary outcomes were days housed and days homeless. Secondary outcomes were mental health status, community adjustment, and costs from 4 perspectives. RESULTS: During a 3-year follow-up, HUD-VASH veterans had 16% more days housed than the case management-only group and 25% more days housed than the standard care group (P<.001 for both). The case management-only group had only 7% more days housed than the standard care group (P =.29). The HUD-VASH group also experienced 35% and 36% fewer days homeless than each of the control groups (P<.005 for both). There were no significant differences on any measures of psychiatric or substance abuse status or community adjustment, although HUD-VASH clients had larger social networks. From the societal perspective, HUD-VASH was 6200 US dollars (15%) more costly than standard care. Incremental cost-effectiveness ratios suggest that HUD-VASH cost 45 US dollars more than standard care for each additional day housed (95% confidence interval, -19 US dollars to 108 US dollars). CONCLUSIONS: Supported housing for homeless people with mental illness results in superior housing outcomes than intensive case management alone or standard care and modestly increases societal costs.
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Administração de Caso/economia , Financiamento Governamental/economia , Pessoas Mal Alojadas/estatística & dados numéricos , Transtornos Mentais/economia , Transtornos Mentais/terapia , Avaliação de Programas e Projetos de Saúde , Habitação Popular/estatística & dados numéricos , Adulto , Administração de Caso/normas , Relações Comunidade-Instituição/economia , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Feminino , Financiamento Governamental/normas , Órgãos Governamentais/economia , Custos de Cuidados de Saúde , Nível de Saúde , Humanos , Masculino , Transtornos Mentais/reabilitação , Estudos Prospectivos , Ajustamento Social , Transtornos Relacionados ao Uso de Substâncias/economia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Estados Unidos , United States Department of Veterans Affairs , Veteranos/estatística & dados numéricosRESUMO
This study utilized data from the national ACCESS program (N = 7224) to investigate the prevalence of suicidal ideation and suicide attempts in a sample of homeless people with mental illness. The prevalence of suicidal ideation in this sample was high (66.2% lifetime prevalence). In addition, 51.3% of the sample reported that they had ever attempted suicide, 26.9% reported an attempt that resulted in a nonpsychiatric hospitalization, and 8% reported an attempt in the previous 30 days. Youth, substance abuse, and psychiatric symptoms were all significantly associated with suicide attempts. Those who reported a recent attempt also reported higher rates of mental health care utilization, particularly inpatient care. The authors conclude that homeless people with mental illness are at particularly high risk for suicidal behavior, however, only in part because of the high prevalence of traditional risk factors.
Assuntos
Pessoas Mal Alojadas/psicologia , Transtornos Mentais/epidemiologia , Suicídio/psicologia , Adolescente , Adulto , Assistência Ambulatorial/estatística & dados numéricos , Serviços Comunitários de Saúde Mental/estatística & dados numéricos , Prestação Integrada de Cuidados de Saúde , Feminino , Acessibilidade aos Serviços de Saúde , Pessoas Mal Alojadas/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Suicídio/estatística & dados numéricos , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Despite reports of high rates of suicidal behavior among mentally ill homeless persons, it remains unknown whether the well-established suicide risks of increased age and comorbid psychiatric and substance abuse disorders ("dual diagnosis") documented in the general population are also markers for increased suicide risk among homeless persons. METHODS: Data from a multi-site outreach program (ACCESS) (N = 7,224) were used to investigate whether rates of serious suicidal ideation and recent suicide attempts varied with the age and substance abuse diagnosis(es) (drug abuse and/or alcohol abuse disorders) among homeless mentally ill clients. RESULTS: The prevalence of 30-day suicidal ideation and suicide attempts (37.5 % and 7.9 %, respectively) was extremely high. Although the risk of serious suicidal ideation and suicide attempts was greater among the younger compared with the older homeless mentally ill clients, risks were not significantly increased by co-morbid alcohol and/or drug abuse. However, a significant interaction between age and co-morbid substance abuse was observed showing that among older clients but not younger clients, those with drug and alcohol abuse were at significantly greater risk of suicidal ideation than those without substance use problems, controlling for confounding factors. CONCLUSION: Efforts to prevent suicide should recognize that among homeless people with mental illness, young-middle-aged (30- to 39-year-old) clients are at greatest risk of suicidal behavior. Among older clients the presence of both drug and alcohol abuse significantly increases suicide risk. These patterns are of special importance because they are quite different from those that are well documented in non-homeless populations.
Assuntos
Pessoas Mal Alojadas/psicologia , Pessoas Mal Alojadas/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Tentativa de Suicídio/psicologia , Tentativa de Suicídio/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/psicologiaRESUMO
PURPOSE: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B). PATIENTS AND METHODS: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children's Cancer Group (CCG) 8881). After initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or regimen B (n = 26). RESULTS: For the entire cohort, the 5-year EFS estimate was 19% (SD = 6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD = 12%), 8% (SD = 5%), and 0%, respectively. Five-year EFS estimates were 20% (SD = 9%) and 19% (SD = 8%) for patients on regimens A and B, respectively (P =.78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for regimen B when compared with regimen A. Outcome was similar for either regimen within disease stages. Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy. CONCLUSION: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was uniformly poor for children with advanced-stage disease treated with either regimen. New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.