RESUMEN
Mesna and its dimer, dimesna, are coadministered for mitigation of ifosfamide- and cisplatin-induced toxicities, respectively. Dimesna is selectively reduced to mesna in the kidney, producing its protective effects. In vitro screens of uptake and efflux transporters revealed saturable uptake by renal organic anion transporters OAT1, OAT3, and OAT4. Efflux transporters breast cancer resistance protein; multidrug and toxin extrusion 1 (MATE1); multidrug resistance proteins MRP1, MRP2, MRP4, and MRP5; and P-glycoprotein (Pgp) significantly reduced dimesna accumulation. Further investigation demonstrated that renal apical efflux transporters MATE1, MRP2, and Pgp were also capable of mesna efflux. Administration of OAT inhibitor probenecid to healthy subjects significantly increased combined mesna and dimesna plasma exposure (91% ± 34%) while decreasing the renal clearance due to net secretion (67.0% ± 12.7%) and steady-state volume of distribution (45.2% ± 13.4%). Thus, the kidney represents a significant sink of total mesna, whereas function of renal drug transporters facilitates clearance in excess of glomerular filtration rate and likely the presence of active mesna in the urine. Loss of renal transporter function due to genetic variability or drug-drug interactions may decrease the efficacy of chemoprotectants, increasing the risk of ifosfamide- and cisplatin-induced toxicities.
Asunto(s)
Riñón/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Mesna/farmacocinética , Sustancias Protectoras/farmacocinética , Adulto , Femenino , Tasa de Filtración Glomerular , Células HeLa , Humanos , Masculino , Mesna/análogos & derivados , Persona de Mediana Edad , Transportadores de Anión Orgánico/metabolismo , Probenecid/farmacología , Distribución Tisular , Adulto JovenRESUMEN
Homeless adults are at high risk for hepatitis B virus (HBV) infection. In addition to culturally sensitive programmes designed to enhance vaccination compliance, accelerated HBV vaccination (three doses over 21 days) have also been suggested to improve compliance among high-risk groups. In this paper, we examined predictors of completers of two of three doses of a HAV/HBV vaccine series, normally delivered over a 6-month period, to simulate compliance with an accelerated series, dosed over 4 weeks. A convenience sample of 865 homeless adults was randomized into a nurse case-managed approach (NCMIT) vs standard programmes with (SIT) and without tracking (SI). Each group was assessed for completion of two of the three dose HAV/HBV vaccine series as well as the full three dose vaccine series. Sixty-eight percent of the NCMIT participants completed the three dose vaccination series at 6 months compared to 61% of SIT participants and 54% of SI participants. Eighty-one percent of the NCMIT participants completed two of the vaccinations compared to 78% of SIT participants and 73% of SI participants. The NCMIT approach resulted in greater numbers of completers of two of three doses and of the full three dose vaccine series. Predictors of completers of two doses and the full three dose vaccine series are provided. A greater number of homeless persons completed two doses across the three groups compared to the three dose vaccine series. The use of nurse case-management and tracking, coupled with an accelerated HAV/HBV vaccination schedule, may optimize vaccination compliance in homeless adults.
Asunto(s)
Vacunas contra la Hepatitis A/administración & dosificación , Hepatitis A/prevención & control , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B/prevención & control , Personas con Mala Vivienda , Cooperación del Paciente/estadística & datos numéricos , Vacunación/métodos , Adulto , Anciano , Simulación por Computador , Femenino , Humanos , Los Angeles , Masculino , Persona de Mediana Edad , Distribución Aleatoria , Factores de Tiempo , Adulto JovenRESUMEN
We showed previously that grapefruit and orange juices inhibited human enteric organic anion-transporting polypeptide (OATP)1A2 in vitro and lowered oral fexofenadine bioavailability clinically. Inhibition of OATP1A2 transport by flavonoids in grapefruit (naringin) and orange (hesperidin) was conducted in vitro. Two randomized, crossover, pharmacokinetic studies were performed clinically. In one study, 120 mg of fexofenadine was ingested with 300 ml grapefruit juice, an aqueous solution of naringin at the same juice concentration (1,200 microM), or water. In the other study, fexofenadine was administered with grapefruit juice, with or 2 h before aqueous suspension of the particulate fraction of juice containing known clinical inhibitors of enteric CYP3A4, but relatively low naringin concentration (34 microM), or with water. Naringin and hesperidin's half-maximal inhibitions were 3.6 and 2.7 microM, respectively. Fexofenadine area under the plasma drug concentration-time curves (AUCs) with grapefruit juice and naringin solution were 55% (P<0.001) and 75% (P<0.05) of that with water, respectively. Fexofenadine AUCs with grapefruit juice and particulate fractions were 57% (P<0.001), 96% (not significant (NS)), and 97% (NS) of that with water, respectively. Individuals tested in both studies (n=9 of 12) had highly reproducible fexofenadine AUC with water (r(2)=0.85, P<0.001) and extent of reduction of it with grapefruit juice (r(2)=0.72, P<0.01). Naringin most probably directly inhibited enteric OATP1A2 to decrease oral fexofenadine bioavailability. Inactivation of enteric CYP3A4 was probably not involved. Naringin appears to have sufficient safety, specificity, and sensitivity to be a clinical OATP1A2 inhibitor probe. Inherent OATP1A2 activity may be influenced by genetic factors. This appears to be the first report of a single dietary constituent clinically modulating drug transport.
Asunto(s)
Citrus paradisi/química , Flavanonas/química , Flavanonas/farmacología , Transportadores de Anión Orgánico/antagonistas & inhibidores , Adulto , Anticoagulantes/farmacología , Bebidas/análisis , Estudios Cruzados , Interpretación Estadística de Datos , Método Doble Ciego , Interacciones Farmacológicas , Femenino , Flavanonas/aislamiento & purificación , Furocumarinas/farmacocinética , Células HeLa , Hesperidina/farmacología , Antagonistas de los Receptores Histamínicos H1/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Terfenadina/análogos & derivados , Terfenadina/farmacocinéticaRESUMEN
The goals of this study were to assess the extent of human intestinal drug transporter expression, determine the subcellular localization of the drug uptake transporter OATP1A2, and then to assess the effect of grapefruit juice consumption on OATP1A2 expression relative to cytochrome P450 3A4 and MDR1. Expression of drug uptake and efflux transporters was assessed using human duodenal biopsy samples. Fexofenadine uptake by different transporters was measured in a transporter-transfected cell line. We investigated the influence of grapefruit juice on pharmacokinetics of orally administered fexofenadine. The effect of grapefruit juice on the expression of intestinal transporters was determined using real-time polymerase chain reaction and Western blot analysis. In the duodenum of healthy volunteers, an array of CYP enzymes as well as uptake and efflux transporters was expressed. Importantly, uptake transporters thought to be liver-specific, such as OATP1B1 and 1B3, as well as OATP2B1 and 1A2 were expressed in the intestine. However, among OATP transporters, only OATP1A2 was capable of fexofenadine uptake when assessed in vitro. OATP1A2 colocalized with MDR1 to the brush border domain of enterocytes. Consumption of grapefruit juice concomitantly or 2 h before fexofenadine administration was associated with reduced oral fexofenadine plasma exposure, whereas intestinal expression of either OATP1A2 or MDR1 remained unaffected. In conclusion, an array of drug uptake and efflux transporters are expressed in the human intestine. OATP1A2 is likely the key intestinal uptake transporter for fexofenadine absorption whose inhibition results in the grapefruit juice effect. Although short-term grapefruit juice ingestion was associated with reduced fexofenadine availability, OATP1A2 or MDR1 expression was unaffected.
Asunto(s)
Bebidas/efectos adversos , Proteínas Portadoras/biosíntesis , Citrus paradisi/efectos adversos , Interacciones Alimento-Droga , Mucosa Intestinal/metabolismo , Preparaciones Farmacéuticas/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Adulto , Anciano , Anciano de 80 o más Años , Disponibilidad Biológica , Western Blotting , Citocromo P-450 CYP3A/biosíntesis , Citocromo P-450 CYP3A/genética , Sistema Enzimático del Citocromo P-450/biosíntesis , Sistema Enzimático del Citocromo P-450/genética , Femenino , Técnica del Anticuerpo Fluorescente , Antagonistas de los Receptores Histamínicos H1/sangre , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Transportadores de Anión Orgánico/biosíntesis , Transportadores de Anión Orgánico/genética , ARN/biosíntesis , ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Terfenadina/análogos & derivados , Terfenadina/sangreRESUMEN
SETTING: Few studies have examined strategies for optimizing adherence to latent tuberculosis infection (LTBI) treatment programs in homeless populations. OBJECTIVES: 1) To compare the effectiveness of an intervention program employing nurse case management and incentives (NCMI) vs. a control program with standard care and incentives on completion of LTBI treatment; and 2) to compare the impact of the two programs on tuberculosis (TB) knowledge among participants. DESIGN: A prospective, two-group site-randomized design conducted among 520 homeless adults residing in the Skid Row region of Los Angeles from 1998 to 2003, assessing completion rates of a 6-month isoniazid (INH) treatment program and change in TB knowledge. RESULTS: Using intent-to-treat analysis, 62% of participants in the intervention program, compared with 39% of controls, completed the full 6-month course of LTBI treatment with INH. Logistic regression modeling revealed that intervention participants had three times greater odds of completing INH treatment than controls. TB knowledge improved in both programs, but the increase was greater among the intervention participants (P < 0.001). CONCLUSIONS: Nurse case management combined with education, incentives, and tracking dramatically improves both adherence to LTBI treatment and TB knowledge in homeless persons compared to a standard approach of outreach and incentives.
Asunto(s)
Antituberculosos/uso terapéutico , Personas con Mala Vivienda , Isoniazida/uso terapéutico , Tuberculosis/tratamiento farmacológico , Adulto , Manejo de Caso , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tuberculosis/enfermeríaRESUMEN
The purpose of this study was to examine the psychosocial, behavioral, and environmental profiles of homeless women, both those with and without a history of victimization, and their intimate partners. Five hundred seven homeless women and their intimate partners participated in the study. Thirty-nine percent of the women reported being physically and/or sexually assaulted as adults. Controlling for potential confounders, victimized women were more likely than others to have a history of childhood sexual and physical abuse, lifetime substance use, greater mental health symptomatology, and current risky sexual activity. Thus, homeless women with mental health and substance abuse problems ought to be screened for violent experiences and encouraged to obtain treatment appropriate to their problems to reduce their ongoing risk of victimization.
Asunto(s)
Violencia Doméstica/psicología , Personas con Mala Vivienda/psicología , Asunción de Riesgos , Mujeres/psicología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicología , Parejas Sexuales , Salud de la MujerRESUMEN
Investigators examined the 6-month impact of three cognitive-behavioral HIV risk-reduction programs on behavioral factors (substance use and sexual risk behaviors) and cognitive and psychological resources of 325 women who resided in emergency or sober-living shelters and their 308 intimate sexual partners. Participants were randomized by shelter to a peer-mentored, a nurse case-managed, or a standard care HIV risk-reduction program. Significant improvements were observed in all groups in all behavioral factors and cognitive and psychological resources except for self-esteem. Participants in the peer-mentored and nurse case-managed groups did not differ significantly from the standard group in self-esteem, life satisfaction, psychological well-being, use of noninjection drugs, sex with multiple partners, and unprotected sex at 6 months (n = 633). It was concluded that a standard approach by health care professionals appears to effectively modify HIV risk behaviors for a majority of homeless participants and may have important economic and policy implications. Further, the impact of short-term programs that address psychological vulnerabilities of impoverished populations needs to be studied further.
Asunto(s)
Manejo de Caso , Infecciones por VIH/enfermería , Infecciones por VIH/prevención & control , Conductas Relacionadas con la Salud , Personas con Mala Vivienda/psicología , Grupo Paritario , Adolescente , Adulto , Femenino , Promoción de la Salud , Humanos , Los Angeles , Masculino , Persona de Mediana Edad , Autoimagen , Parejas Sexuales , Apoyo Social , Salud Urbana , Salud de la MujerRESUMEN
MDR1 (P-glycoprotein) is an important factor in the disposition of many drugs, and the involved processes often exhibit considerable interindividual variability that may be genetically determined. Single-strand conformational polymorphism analysis and direct sequencing of exonic MDR1 deoxyribonucleic acid from 37 healthy European American and 23 healthy African American subjects identified 10 single nucleotide polymorphisms (SNPs), including 6 nonsynonymous variants, occurring in various allelic combinations. Population frequencies of the 15 identified alleles varied according to racial background. Two synonymous SNPs (C1236T in exon 12 and C3435T in exon 26) and a nonsynonymous SNP (G2677T, Ala893Ser) in exon 21 were found to be linked (MDR1*2 ) and occurred in 62% of European Americans and 13% of African Americans. In vitro expression of MDR1 encoding Ala893 (MDR1*1 ) or a site-directed Ser893 mutation (MDR1*2 ) indicated enhanced efflux of digoxin by cells expressing the MDR1-Ser893 variant. In vivo functional relevance of this SNP was assessed with the known P-glycoprotein drug substrate fexofenadine as a probe of the transporter's activity. In humans, MDR1*1 and MDR1*2 variants were associated with differences in fexofenadine levels, consistent with the in vitro data, with the area under the plasma level-time curve being almost 40% greater in the *1/*1 genotype compared with the *2/*2 and the *1/*2 heterozygotes having an intermediate value, suggesting enhanced in vivo P-glycoprotein activity among subjects with the MDR1*2 allele. Thus allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P-glycoprotein function.
Asunto(s)
Población Negra/genética , Genes MDR/genética , Polimorfismo de Nucleótido Simple , Terfenadina/farmacocinética , Población Blanca/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , África/etnología , Alelos , Antialérgicos/farmacocinética , Área Bajo la Curva , Clonación Molecular , Cartilla de ADN , Digoxina/farmacocinética , Inhibidores Enzimáticos/farmacocinética , Europa (Continente)/etnología , Variación Genética , Genotipo , Haplotipos , Humanos , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Terfenadina/análogos & derivados , Factores de TiempoRESUMEN
Findings are presented for a cross-sectional study of serological markers of hepatitis B virus (HBV) infection in an underserved population-impoverished veterans of the US armed forces in a Veterans Administration (VA) residential program in the US. We examine the demographic, background, and risk factors associated with HBV infection in this high-risk population. This paper presents a secondary analysis of cross-sectional survey and clinical data for 370 male veterans who were residents of a domiciliary care program for homeless veterans in Los Angeles, using chi(2), Fisher's Exact, and logistic regression analysis. About one-third (30.8%) of the sample tested positive for current or past HBV infection (ie, seropositive for either the HBV core antibody or surface antigen). After multivariate analysis, rates of HBV were significantly higher among veterans who were older, non-white, or who had a history of regular heroin use (a proxy measure for injection drug use), drug overdose, or drug detoxification treatment. The rate of current or past HBV infection among veterans in this sample (30.8%) was high compared to an estimated 5% to 8% of the general US population. Also, 3% of the sample were currently infected with HBV. Strategies for intervention include broader screening, immunization, and treatment interventions with this high-risk group.
Asunto(s)
Hepatitis B/epidemiología , Personas con Mala Vivienda/estadística & datos numéricos , Instituciones Residenciales , Veteranos/estadística & datos numéricos , Adulto , Estudios Transversales , Humanos , Los Angeles/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
The human organic anion transporting polypeptide-C (OATP-C) (gene SLC21A6) is a liver-specific transporter importantly involved in the hepatocellular uptake of a variety of endogenous and foreign chemicals. In this study, we demonstrate the presence of multiple functionally relevant single-nucleotide polymorphisms (SNPs) in OATP-C in a population of African- and European-Americans. Moreover, examination of 14 nonsynonymous polymorphisms indicated that genotypic frequencies were dependent on race. Functional assessment of 16 OATP-C alleles in vitro revealed that several variants exhibited markedly reduced uptake of the OATP-C substrates estrone sulfate and estradiol 17beta-d-glucuronide. Specifically, alterations in transport were associated with SNPs that introduce amino acid changes within the transmembrane-spanning domains (T217C (Phe-73 --> Leu), T245C (Val-82 --> Ala), T521C (Val-174 --> Ala), and T1058C (Ile-353 --> Thr)) and also with those that modify extracellular loop 5 (A1294G (Asn-432 --> Asp), A1385G (Asp-462 --> Gly), and A1463C (Gly-488 --> Ala)). Cell surface biotinylation experiments indicated that the altered transport activity of some OATP-C variants was due, in part, to decreased plasma membrane expression. Given the relatively high genotypic frequency of the T521C (14%) transition in European-Americans and the G1463C (9%) transversion in African-Americans, SNPs in OATP-C may represent a heretofore unrecognized factor influencing drug disposition.
Asunto(s)
Alelos , Población Negra/genética , Proteínas Portadoras/genética , Variación Genética , Polimorfismo Genético , Población Blanca/genética , Secuencia de Aminoácidos , Proteínas de Transporte de Anión , Secuencia de Bases , Cartilla de ADN , Europa (Continente) , Haplotipos , Células HeLa , Humanos , Transporte Iónico/genética , Datos de Secuencia Molecular , Mutagénesis Sitio-DirigidaRESUMEN
Lifetime contraceptive use as reported by a representative sample of 764 homeless women in Los Angeles was examined overall and for different age and ethnic subgroups and contrasted with expressed willingness to use specific methods. Over 80% of the women reported condom use. However, less than 5% had ever used female condoms, although 38% of the overall sample and 73% of the teenagers said they were willing to try them. Similar gaps between reported use and endorsement were found for other particular methods. Native Americans had relatively low use of virtually all contraceptive methods, and over 80% of African-Americans rejected implants. Our findings suggest that age-related factors and ethno-cultural perceptions may deter some homeless women from using contraception. In any case, gaps between realized use and willingness to use may represent missed opportunities to prevent the high rates of unintended pregnancies and sexually transmitted infections found among homeless women.
Asunto(s)
Conducta Anticonceptiva/psicología , Anticoncepción/métodos , Personas con Mala Vivienda/psicología , Embarazo no Deseado/psicología , Enfermedades de Transmisión Sexual/prevención & control , Adolescente , Adulto , Factores de Edad , California/etnología , Características Culturales , Etnicidad/psicología , Femenino , Humanos , Aceptación de la Atención de Salud/psicología , EmbarazoRESUMEN
BACKGROUND: To assess the concordance of homeless women's self-reported drug use with objective data. OBJECTIVE: To determine whether objective data (e.g., hair assays) are necessary supplements to self reports in assessing homeless women's cocaine use. METHOD: Self reports of cocaine use by 1,037 homeless women were compared to objective data based on radioimmunoassay of hair; independent correlates of cocaine use and underreporting were assessed using logistic regression. RESULTS: Forty-two percent of the women self-reported cocaine use in the past 6 months, whereas 49% had positive hair assays. Over 25% underreported cocaine use; however, underreporting decreased as hair cocaine levels increased. Predictors of underreporting included being Latino, younger and living primarily in shelters. Nevertheless, independent predictors of self-reported cocaine use and positive hair assays were identical. CONCLUSION: Homeless women's self-reports of cocaine use are fairly accurate. Objective data are particularly critical for assessing cocaine use among subgroups who are fearful of sanctions or use cocaine relatively infrequently or in smaller amounts.
Asunto(s)
Trastornos Relacionados con Cocaína/epidemiología , Cabello/química , Personas con Mala Vivienda , Autorrevelación , Adulto , Escolaridad , Femenino , Humanos , Modelos Logísticos , Los Angeles/epidemiología , Radioinmunoensayo , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: The goal of this study was to develop a diabetes-specific scale of patient desire to participate in medical decision making (DPMD) and examine its internal consistency reliability, stability, and validity (content, discriminant, convergent, and construct). METHODS: In a cross-sectional study, 65 patients with type 2 diabetes from a teaching hospital's general medical clinic were interviewed at baseline and 2 weeks later to measure their DPMD scores. Data were collected on demographic/clinical features, health value, social support, desire to make a final decision, and value of patient autonomy. RESULTS: Of the 11 DPMD items, 2 distinct factors emerged representing desire for discussion and desire for information. The DPMD scale had high internal consistency reliability, was stable over 2 weeks and demonstrated good content validity. DPMD scale items were more correlated with each other than with health value or social support. Overall, patients who obtained diabetes education reported greater desire to participate in decisions. Younger patients had a greater overall desire for discussion. The DPMD desire for discussion subscale correlated with patients' desire to make the final treatment decision but not with patients' value of autonomy. CONCLUSIONS: The DPMD is a brief, reliable, valid measure for assessing patient desire to participate in diabetes medical decision making.
Asunto(s)
Actitud Frente a la Salud , Diabetes Mellitus Tipo 2/psicología , Participación del Paciente , Relaciones Médico-Paciente , Comunicación , Estudios Transversales , Etnicidad , Humanos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estados UnidosRESUMEN
BACKGROUND: Information about whether specific types of support are associated with poor psychosocial profiles, health behaviors, and positive use of medical care is critical for identifying homeless women at highest risk for negative outcomes. OBJECTIVES: This study aimed to examine the impact that various levels of support from substance users and nonusers have on homeless women's psychosocial profiles, health and health behaviors, and use of health services. METHODS: This cross-sectional survey used a sample of 1,302 sheltered homeless women. Using controls for potential confounders, outcomes were compared across four mutually exclusive subgroups of women reporting support from substance users only (n = 58), substance nonusers only (n = 439), both users and nonusers (n = 136), and no one (n = 669). Structured and psychometrically sound instruments measured social support, substance use, self-esteem, coping, and psychological symptoms. Additional instruments measured sociodemographic characteristics, sexual risk behavior, health status, and use of health services. RESULTS: As compared with those who have little or no support, women whose support included substance nonusers reported better psychosocial profiles and somewhat greater use of health services. Support from substance nonusers only was associated with better health behaviors and greater use of health services. Support from substance users only was essentially equivalent to not having support. CONCLUSION: Modifying the social networks of homeless women appears to be associated with improved mental health outcomes, less risky health behaviors, and greater use of health services.
Asunto(s)
Conductas Relacionadas con la Salud , Personas con Mala Vivienda , Apoyo Social , Adaptación Psicológica , Adulto , Análisis de Varianza , Estudios Transversales , Escolaridad , Femenino , Servicios de Salud/estadística & datos numéricos , Humanos , Los Angeles/epidemiología , Estado Civil , Autoimagen , Aislamiento Social , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
OBJECTIVE: To contrast sociodemographic characteristics, physical and mental health status, substance use, sexual behaviors, victimization, and utilization of health services between homeless women residing in sheltered and non-sheltered environments. DESIGN: Cross-sectional survey. A structured scale was used to measure mental health status. Physical health status, substance use, sexual behavior, history of adult victimization, and health services utilization were measured by content-specific items. SETTING: Shelters (N = 47) and outdoor locations in Los Angeles. PARTICIPANTS: One thousand fifty-one homeless women. RESULTS: Homeless women living on the streets were more likely than sheltered women to be white and longer-term homeless. Controlling for sociodemographic characteristics, multiple logistic regression analyses revealed that unsheltered women had over 3 times greater odds of fair or poor physical health, and over 12 times greater odds of poor mental health than sheltered homeless women. They were also more likely than sheltered women to report using alcohol or noninjection drugs, to have multiple sexual partners, and to have a history of physical assault. About half of the overall sample reported utilization of a variety of health services; however, unsheltered homeless women were less likely to utilize all of the health services that were assessed, including drug treatment. CONCLUSIONS: There is a critical need for aggressive outreach programs that provide mental health services and substance abuse treatment for homeless women on the streets. Comprehensive services that also include medical care, family planning, violence prevention, and behavioral risk reduction may be particularly valuable for homeless women, especially those living in unsheltered environments.
Asunto(s)
Servicios de Salud/estadística & datos numéricos , Personas con Mala Vivienda/estadística & datos numéricos , Adulto , Mujeres Maltratadas , Estudios Transversales , Atención a la Salud , Femenino , Vivienda , Humanos , Modelos Logísticos , Los Angeles/epidemiología , Factores de Riesgo , Conducta Sexual/estadística & datos numéricos , Factores Socioeconómicos , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
CONTEXT: Patients with rheumatoid arthritis are at risk for substantial morbidity because of their arthritis and premature mortality due to comorbid diseases. However, little is known about the quality of the health care that these patients receive. OBJECTIVE: To assess the quality of the health care that rheumatoid arthritis patients receive for their arthritis, comorbid diseases, and health care maintenance and to determine the effect of patterns of specialty care on quality. DESIGN, SETTING, AND PARTICIPANTS: Historical cohort study of 1355 adult rheumatoid arthritis patients enrolled in the fee-for-service or discounted fee-for-service plans of a nationwide US insurance company. Patients were identified and followed up through administrative data between 1991 and 1995. MAIN OUTCOME MEASURES: Quality scores for arthritis, comorbid disease, and health care maintenance were developed from performance on explicit process measures that related to each of these domains and described the percentage of indicated health care processes performed within each domain during each person-year of the study. RESULTS: During 4598 person-years of follow-up, quality scores were 62% (95% confidence interval [CI], 61%-64%) for arthritis care, 52% (95% CI, 49%-55%) for comorbid disease care, and 42% (95% CI, 40%-43%) for health care maintenance. Across domains, care patterns including relevant specialists yielded performance scores 30% to 187% higher than those that did not (P<.001) and 45% to 67% of person-years were associated with patterns of care that did not include a relevant specialist. Presence of primary care without specialty care yielded health care maintenance scores that were 43% higher than those for patterns that included neither primary nor relevant specialty care (P<.001). CONCLUSIONS: In this population, health care quality appears to be suboptimal for arthritis, comorbid disease, and health care maintenance. Patterns of care that included relevant specialists were associated with substantially higher quality across all domains. Patterns that included generalists were associated with substantially higher quality health care maintenance than patterns that included neither a generalist nor a relevant specialist. The optimal roles of primary care physicians and specialists in the care of patients with complex conditions should be reassessed. JAMA. 2000;284:984-992
Asunto(s)
Artritis Reumatoide/terapia , Calidad de la Atención de Salud , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/economía , Artritis Reumatoide/epidemiología , Estudios de Cohortes , Comorbilidad , Medicina Familiar y Comunitaria , Planes de Aranceles por Servicios , Femenino , Humanos , Modelos Logísticos , Masculino , Medicina , Persona de Mediana Edad , Calidad de la Atención de Salud/economía , Especialización , Estados UnidosRESUMEN
HIV protease inhibitors have proven remarkably effective in treating HIV-1 infection. However, some tissues such as the brain and testes (sanctuary sites) are possibly protected from exposure to HIV protease inhibitors due to drug entry being limited by the membrane efflux transporter P-glycoprotein, located in the capillary endothelium. Intravenous administration of the novel and potent P-glycoprotein inhibitor LY-335979 to mice (1-50 mg/kg) increased brain and testes concentration of [(14)C]nelfinavir, up to 37- and 4-fold, respectively, in a dose-dependent fashion. Similar effects in brain levels were also observed with (14)C-labeled amprenavir, indinavir, and saquinavir. Because [(14)C]nelfinavir plasma drug levels were only modestly increased by LY-335979, the increase in brain/plasma and testes/plasma ratios of 14- to 17- and 2- to 5-fold, respectively, was due to increased tissue penetration. Less potent P-glycoprotein inhibitors like valspodar (PSC-833), cyclosporin A, and ketoconazole, as well as quinidine and verapamil, had modest or little effect on brain/plasma ratios but increased plasma nelfinavir concentrations due to inhibition of CYP3A-mediated metabolism. Collectively, these findings provide "proof-of-concept" for increasing HIV protease inhibitor distribution into pharmacologic sanctuary sites by targeted inhibition of P-glycoprotein using selective and potent agents and suggest a new therapeutic strategy to reduce HIV-1 viral replication.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/antagonistas & inhibidores , Encéfalo/metabolismo , Dibenzocicloheptenos/farmacología , Inhibidores de la Proteasa del VIH/farmacocinética , Quinolinas/farmacología , Testículo/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Células CACO-2 , Humanos , Concentración 50 Inhibidora , Masculino , RatonesRESUMEN
There is limited understanding of the physical health, mental health, and substance use or abuse correlates of sexual violence against homeless women. This study documents the association of rape with health and substance use or abuse characteristics reported by a probability sample of 974 homeless women in Los Angeles. Controlling for potential confounders, women who reported rape fared worse than those who did not on every physical and mental health measure and were also more likely to have used and abused drugs other than alcohol. Results should serve to alert clinicians about groups of homeless women who may benefit from rape screening and treatment interventions.
Asunto(s)
Estado de Salud , Personas con Mala Vivienda , Violación , Adolescente , Adulto , Femenino , Humanos , Modelos Logísticos , Trastornos Relacionados con SustanciasRESUMEN
OBJECTIVES: (1) To present the Behavioral Model for Vulnerable Populations, a major revision of a leading model of access to care that is particularly applicable to vulnerable populations; and (2) to test the model in a prospective study designed to define and determine predictors of the course of health services utilization and physical health outcomes within one vulnerable population: homeless adults. We paid particular attention to the effects of mental health, substance use, residential history, competing needs, and victimization. METHODS: A community-based probability sample of 363 homeless individuals was interviewed and examined for four study conditions (high blood pressure, functional vision impairment, skin/leg/foot problems, and tuberculosis skin test positivity). Persons with at least one study condition were followed longitudinally for up to eight months. PRINCIPAL FINDINGS: Homeless adults had high rates of functional vision impairment (37 percent), skin/leg/foot problems (36 percent), and TB skin test positivity (31 percent), but a rate of high blood pressure similar to that of the general population (14 percent). Utilization was high for high blood pressure (81 percent) and TB skin test positivity (78 percent), but lower for vision impairment (33 percent) and skin/leg/foot problems (44 percent). Health status for high blood pressure, vision impairment, and skin/leg/foot problems improved over time. In general, more severe homeless status, mental health problems, and substance abuse did not deter homeless individuals from obtaining care. Better health outcomes were predicted by a variety of variables, most notably having a community clinic or private physician as a regular source of care. Generally, use of currently available services did not affect health outcomes. CONCLUSIONS: Homeless persons are willing to obtain care if they believe it is important. Our findings suggest that case identification and referral for physical health care can be successfully accomplished among homeless persons and can occur concurrently with successful efforts to help them find permanent housing, alleviate their mental illness, and abstain from substance abuse.
Asunto(s)
Conductas Relacionadas con la Salud , Accesibilidad a los Servicios de Salud/normas , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Estado de Salud , Personas con Mala Vivienda/psicología , Modelos Psicológicos , Modelos Estadísticos , Evaluación de Resultado en la Atención de Salud/organización & administración , Aceptación de la Atención de Salud/psicología , Adolescente , Adulto , Anciano , Femenino , Necesidades y Demandas de Servicios de Salud/tendencias , Investigación sobre Servicios de Salud , Personas con Mala Vivienda/estadística & datos numéricos , Humanos , Modelos Lineales , Modelos Logísticos , Los Angeles , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Aceptación de la Atención de Salud/estadística & datos numéricos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Adequate bile flow, maintained in part by the efficient enterohepatic recirculation of bile acids, is critical for normal liver function. One important component of this process is the uptake of bile acids from the portal circulation into hepatocytes by the bile acid uptake transporter sodium taurocholate cotransporting polypeptide (NTCP). Thus, the expression and functional activity of this transporter may affect the rate of bile acid removal from the portal circulation. Accordingly, we assessed NTCP mRNA expression from human livers using a sensitive RNase protection assay. In addition, the ability of various bile acids and drugs to inhibit NTCP activity was determined using a recombinant vaccinia expression system. A 40-fold interindividual variability was found in NTCP mRNA levels determined in eight liver samples of disease-free donors. Expressed NTCP exhibited high-affinity, sodium-dependent uptake of taurocholate, and as expected, this was markedly inhibited by bile acids and organic anions. A number of drugs, including peptidomimetic renin inhibitors, propranolol, cyclosporin, and progesterone, were found to be potent inhibitors, whereas antiarrhythmic agents, including bupivicaine, lidocaine, and quinidine, were found to enhance NTCP activity. Accordingly, these results indicate that large interindividual variability exists in NTCP mRNA level and that a number of drugs currently in clinical use have the potential to interact with and alter NTCP activity, thereby affecting hepatic bile acid uptake.