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BACKGROUND: Dementia affects 55 million people worldwide and low muscle mass may be associated with cognitive decline. Mid-arm muscle circumference (MAMC) correlates with dual-energy Xray absorptiometry and bioelectrical impedance analyses, yet are not routinely available. Therefore, we examined the association between MAMC and cognitive performance in older adults. METHODS: We included community-dwelling adults ≥55 years from the China Health and Nutrition Survey. Cognitive function was estimated based on a subset of the modified Telephone Interview for Cognitive Status (0-27, low-high) during years (1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, 2015, 2018). A multivariable linear mixed-effects model was used to test whether MAMC was associated with rate of cognitive decline across age groups and cognitive function overall. RESULTS: Of 3702 adults (53% female, 63.2 ± 7.3 years), mean MAMC was 21.4 cm ± 3.0 and baseline cognitive score was 13.6 points ±6.6. We found no evidence that the age-related rate of cognitive decline differed by MAMC (P = .77). Declines between 5-year age groups ranged from -.80 [SE (standard error) .18] to -1.09 [.22] for those at a mean MAMC, as compared to -.86 [.25] to -1.24 [.31] for those at a 1 MAMC 1 standard deviation above the mean. Higher MAMC was associated with better cognitive function with .13 [.06] higher scores for each corresponding 1 standard deviation increase in MAMC across all ages. CONCLUSION: Higher MAMC at any age was associated with better cognitive performance in older adults. Understanding the relationship between muscle mass and cognition may identify at-risk subgroups needing targeted interventions to preserve cognition.
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BACKGROUND: There is a close relationship between weight status and cognitive impairment in older adults. This study examined the association between weight status and the trajectory of cognitive decline over time in a population-based cohort of older adults in China. METHODS: We used data from adults aged ≥55 years participating in the China health and nutrition survey (1997-2018). Underweight (body mass index [BMI] ≤ 18.5 kg/m2), normal weight (18.5-23 kg/m2), overweight (23-27.5 kg/m2), and obesity (BMI ≥ 27.5 kg/m2) were defined using the World Health Organization Asian cutpoints. Global cognition was estimated every 2-4 years through a face-to-face interview using a modified telephone interview for cognitive status (scores 0-27). The association between BMI and the rate of global cognitive decline, using a restricted cubic spline for age and age category, was examined with linear mixed-effects models accounting for correlation within communities and individuals. RESULTS: We included 5 992 adults (53% female participants, mean age of 62 at baseline). We found differences in the adjusted rate of global cognitive decline by weight status (p = .01 in the cubic spline model). Models were adjusted for sex, marital status, current employment status, income, region, urbanization, education status, birth cohort, leisure activity, smoking status, and self-reported diagnosis of hypertension, diabetes, or Myocardial Infarction (MI)/stroke. In addition, significant declines by age in global cognitive function were found for all weight status categories except individuals with obesity. CONCLUSIONS: In a cohort of adults in China, cognitive decline trajectory differed by weight status. A slower rate of change was observed in participants classified as having obesity.
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Disfunción Cognitiva , Obesidad , Humanos , Femenino , Anciano , Masculino , Obesidad/complicaciones , Obesidad/epidemiología , Sobrepeso , Índice de Masa Corporal , Disfunción Cognitiva/epidemiología , Encuestas Nutricionales , China/epidemiologíaRESUMEN
Metabolic syndrome and its associated conditions, such as obesity and type 2 diabetes mellitus (T2DM), are a major public health issue in modern societies. Dietary interventions, including microbiota-directed foods which effectively modulate the gut microbiome, may influence the regulation of obesity and associated comorbidities. Although research on probiotics and prebiotics has been conducted extensively in recent years, diets with the use of synbiotics remain relatively unexplored. Here, we investigated the effects of a novel synbiotic intervention, consisting of an adlay seed extrusion cooked (ASEC)-based prebiotic and probiotic (Lactobacillus paracasei and Bacillus coagulans) on metabolic disorders and microbial dysbiosis in high-fat diet (HFD)-induced obese mice. The ASEC-based synbiotic intervention helped improve HFD-induced body weight gain, hyperlipidemia, impaired glucose tolerance, insulin resistance, and inflammation of the adipose and liver tissues. In addition, data from fecal metagenomics indicated that the ASEC-based synbiotic intervention fostered reconstitution of gut bacterial diversity and composition in HFD-induced obese mice. In particular, the ASEC-based synbiotic intervention increased the relative abundance of families Ruminococcaceae and Muribaculaceae and order Bacteroidales and reduced that of families Lactobacillaceae, Erysipelotrichaceae, and Streptococcaceae in HFD-induced obese mice. Collectively, our results suggest that delayed dietary intervention with the novel ASEC-based synbiotic ameliorates HFD-induced obesity, metabolic disorders, and dysbiosis.
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Dieta Alta en Grasa/efectos adversos , Disbiosis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Prebióticos , Probióticos , Simbióticos , Tejido Adiposo , Alimentación Animal/análisis , Animales , Bacterias/clasificación , Bacterias/genética , Peso Corporal , Dislipidemias , Resistencia a la Insulina , Masculino , Ratones , Obesidad/inducido químicamenteRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is common worldwide and closely associated with metabolic dysfunction. NAFLD leads to a higher risk of development of severe liver diseases, such as nonalcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma (HCC). To date, no pharmacotherapy targeting NAFLD has received general approval. Adlay is a plant that has been used as traditional herbal medicine in Asia and is a promising candidate to solve this global issue. We have established a mouse model of NAFLD by feeding a high-fat diet (HFD) for 10 weeks. Here, ethanolic or water extracts of adlay seed (ASE and ASW, respectively), mixed with HFD, were fed to the mice for 10 weeks. The ASE and ASW treatment ameliorated hyperglycemia and improved the glucose tolerance and insulin resistance in the HFD mice. Hyperlipidemia in HFD mice was prevented by the ASE and ASW diet. In addition, the ASE and ASW supplementation attenuated hepatic steatosis and inflammation, improved liver function, and caused no harm to the kidneys. Moreover, the mechanism of the effect of ASE and ASW on inhibiting hepatic lipogenesis and inducing fatty acid ß-oxidation was certified by the simulated human fatty liver cell model. Our study showed the regulatory potential of the extracts of adlay seeds for alleviating NAFLD, as well as related liver and metabolic diseases.
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BACKGROUND: Dietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear. METHODS: This study was conducted to examine the therapeutic effect of GBHT on fat-induced obesity, hepatic steatosis, and insulin resistance in mice. RESULTS: GBHT protected mice against HFD-induced body weight gain, hyperlipidemia, and hyperglycemia compared with mice that were not treated. GBHT inhibited the expansion of adipose tissue and adipocyte hypertrophy. No ectopic fat deposition was found in the livers of HFD mice treated with GBHT. In addition, glucose intolerance and insulin sensitivity in HFD mice was also improved by GBHT. CONCLUSION: GBHT prevents changes in lipid and carbohydrate metabolism in a HFD mouse model. Our findings provide evidence for the traditional use of GBHT as therapy for the management of metabolic syndrome.
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We used full-system-estimation instrumental-variables simultaneous equations modeling (IV-SEM) to examine physical activity relative to body mass index (BMI; weight (kg)/height (m)(2)) using 25 years of data (1985/1986 to 2010/2011) from the Coronary Artery Risk Development in Young Adults (CARDIA) Study (n = 5,115; ages 18-30 years at enrollment). Neighborhood environment and sociodemographic instruments were used to characterize physical activity, fast-food consumption, smoking, alcohol consumption, marriage, and childbearing (women) and to predict BMI using semiparametric full-information maximum likelihood estimation to control for unobserved time-invariant and time-varying residual confounding and differential measurement error through model-derived discrete random effects. Comparing robust-variance ordinary least squares, random-effects regression, fixed-effects regression, single-equation-estimation IV-SEM, and full-system-estimation IV-SEM, estimates from random- and fixed-effects models and the full-system-estimation IV-SEM were unexpectedly similar, despite the lack of control for residual confounding with the random-effects estimator. Ordinary least squares tended to overstate the significance of health behaviors in BMI, while results from single-equation-estimation IV-SEM were notably different, revealing the impact of weak instruments in standard instrumental-variable methods. Our robust findings for fixed effects (which does not require instruments but has a high cost in lost degrees of freedom) and full-system-estimation IV-SEM (vs. standard IV-SEM) demonstrate potential for a full-system-estimation IV-SEM method even with weak instruments.
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Índice de Masa Corporal , Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios/fisiopatología , Ejercicio Físico , Conductas Relacionadas con la Salud/fisiología , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Enfermedad de la Arteria Coronaria/prevención & control , Vasos Coronarios/patología , Comida Rápida/efectos adversos , Femenino , Humanos , Análisis de los Mínimos Cuadrados , Funciones de Verosimilitud , Estudios Longitudinales , Masculino , Estado Civil , Modelos Biológicos , Estudios Multicéntricos como Asunto , Factores Protectores , Historia Reproductiva , Características de la Residencia , Medición de Riesgo/métodos , Fumar/efectos adversos , Adulto JovenRESUMEN
In this chapter, we report on the analyses focusing on both quality thresholds and quality features. First, we address questions about quality thresholds, using two analytic approaches. The analyses ask whether there is evidence suggesting thresholds in the association between a specific quality measure and a specific child outcome. Second, we extend these analyses to ask whether each child outcome is more strongly related to global quality measures or to quality measures that measure teacher-child interactions or quality of instruction in a given content area. The research to date provides the basis for the articulation of two hypotheses related to quality thresholds and features: (1) the quality of ECE is a stronger predictor of residualized gains in child outcomes in classrooms with higher quality than in classrooms with lower quality and (2) more specific measures of quality are stronger predictors of residualized gains in child outcomes than are global measures. We turn now to analyses intended to address these hypotheses by using data from several data sets.
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Cuidado del Niño/normas , Intervención Educativa Precoz/normas , Cuidado del Niño/métodos , Preescolar/educación , Intervención Educativa Precoz/métodos , Estudios de Evaluación como Asunto , Humanos , Metaanálisis como Asunto , Modelos PsicológicosRESUMEN
Prenatal cocaine exposure can alter the postnatal care received by rat pups. Such effects could be caused in part by alterations in pup-produced stimuli that elicit early postnatal maternal care. Pup ultrasonic vocalizations are thought to be a particularly salient stimulus, and when paired with other cues, may elicit maternal attention. Cocaine is known to acutely alter thermoregulatory and cardiac function, thus prenatal cocaine may affect vocalizations through altering these functions. The data presented here determine the impact of full term prenatal cocaine exposure, saline exposure, or no exposure on thermogenic capacity, cardiac function, and the resulting ultrasonic vocalizations across the early postnatal period (days 1-5). Results indicated that while sharing many similar characteristics with saline-exposed and untreated animals, prenatal cocaine exposure was associated with specific alterations in vocalization characteristics on postnatal day 1 (PND 1), including call amplitude. Furthermore, numerous spectral parameters of their vocalizations were found altered on PND 3, including rate, call duration, and frequency, while no alterations were found on PND 5. Additionally, cocaine-exposed pups also showed a reduced thermoregulatory capacity compared to saline animals and reduced cardiac mass compared to untreated animals on PND 5. Together, these findings indicate that prenatal cocaine may be altering the elicitation of maternal care through its impact on vocalizations and thermoregulation, and suggests a potential mechanism for these effects through cocaine's impact on developing stress systems.
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BACKGROUND: To assess factors associated with having a Trichomonas vaginalis (TV) infection among persons receiving care for human immunodeficiency virus (HIV) and estimate the number of transmitted HIV infections attributable to TV. METHODS: HIV clinic patients were recruited from 2 secondary prevention studies, screened by urine nucleic-acid amplification tests for sexually transmitted infections, and interviewed about risk factors (baseline, 6, and 12 months). We conducted mathematical modeling of the results to estimate the number of transmitted HIV infections attributable to TV among a cohort of HIV-infected patients receiving medical care in North Carolina. RESULTS: TV was prevalent in 7.4%, and incident in 2% to 3% of subjects at follow-up. Individuals with HIV RNA <400 copies/mL (odds ratio, 0.32; 95% CI: 0.14-0.73) and at least 13 years of education (odds ratio, 0.24; 95% CI: 0.08-0.70) were less likely to have TV. Mathematical modeling predicted that 0.062 HIV transmission events occur per 100 HIV-infected women in the absence of TV infection and 0.076 HIV infections per 100 HIV- and TV-infected women (estimate range: 0.070-0.079), indicating that 23% of the HIV transmission events from HIV-infected women may be attributable to TV infection when 22% of women are coinfected with TV. CONCLUSIONS: The data suggest the need for improved diagnosis of TV infection and suggest that HIV-infected women in medical care may be appropriate targets for enhanced testing and treatment.
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Seropositividad para VIH/epidemiología , Modelos Teóricos , Conducta Sexual/estadística & datos numéricos , Tricomoniasis/epidemiología , Trichomonas vaginalis/patogenicidad , Carga Viral/estadística & datos numéricos , Adulto , Estudios de Cohortes , Escolaridad , Femenino , Estudios de Seguimiento , Seropositividad para VIH/diagnóstico , Seropositividad para VIH/transmisión , Humanos , Activación de Linfocitos , Masculino , North Carolina/epidemiología , Prevalencia , Factores de Riesgo , Tricomoniasis/diagnóstico , Tricomoniasis/transmisión , Esparcimiento de VirusRESUMEN
AIM: Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians. MATERIALS & METHODS: CYP450 2B6, 2D6, 3A4 and 3A5, ABCB1 and constitutive androstane receptor and pregnane X receptor, were analyzed for polymorphisms in 26 subjects. RESULTS: Allele frequencies (variant) were: CYP2B6 514G>T (0.31) CYP2D6*4 (0.02); CYP2D6*17 (0.35); CYP3A4*1B (0.77); CYP3A5*3 (0.25); ABCB1 2677G>T (0.0), ABCB1 3435C>T (0.21), NR1I3 13711152T>C (0.02), NR1I2 44477T>C (0.10), NR1I2 63396C>T (0.33), NR1I2 6-bp indel (del: 0.17). CYP2B6 516G>T (non-wild-type/wild-type) correlated with nevirapine pharmacokinetic parameters; geometric mean ratios (95% CI): 1.75 (1.27-2.40) for area under the concentration time curve (AUC)(0-12 h), 1.58 (1.03-2.42) for C(0), and 0.53 (0.31-0.91) for clearance. In a multivariable model, nevirapine AUC increased by 1.5% per year of age (p < 0.0001), CYP2B6 516 T allele increased AUC by 92% (p < 0.0001), and CYP3A5*3 decreased AUC by 31% (p = 0.0027). CONCLUSION: Allele frequencies were similar to other sub-Saharan African populations. The T allele for CYP2B6 516 was significantly associated with nevirapine exposure.
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Fármacos Anti-VIH/farmacocinética , Hidrocarburo de Aril Hidroxilasas/genética , Frecuencia de los Genes/genética , Nevirapina/farmacocinética , Oxidorreductasas N-Desmetilantes/genética , Subfamilia B de Transportador de Casetes de Unión a ATP , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Adulto , África del Sur del Sahara , Alelos , Fármacos Anti-VIH/uso terapéutico , Área Bajo la Curva , Receptor de Androstano Constitutivo , Ciclofilinas/genética , Citocromo P-450 CYP2B6 , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Nevirapina/uso terapéutico , Polimorfismo de Nucleótido Simple , Receptor X de Pregnano , Receptores Citoplasmáticos y Nucleares/genética , Receptores de Esteroides/genéticaRESUMEN
Single-incision laparoscopic surgery is a new approach considered as an alternative to natural orifice transluminal endoscopic surgery. Here, we describe a novel technique for laparoscopic adjustable gastric banding (LAGB) using a single-incision transumbilical (SITU) approach and an intraoperative method for liver retraction. Three patients (18 to 23 y) with a mean body mass index of 38.1 kg/m2 underwent LAGB with the "pars flaccida" technique through an SITU approach. Retraction of the left liver lobe was achieved with a specially designed "liver suspension tape" attached with sutures to the left upper quadrant abdominal wall and midline. The mean operative time was 62 minutes, with no intraoperative complications. These patients responded well postoperatively and were discharged after 2 days. SITU-LAGB is a safe, technically feasible, and reproducible procedure resulting in a more beneficial cosmetic appearance as the incision wound is hidden in the umbilicus, thus avoiding visible abdominal scars.
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Gastroplastia/métodos , Laparoscopía/métodos , Obesidad Mórbida/cirugía , Adolescente , Femenino , Humanos , Hígado/cirugía , Masculino , Técnicas de Sutura , Tracción/métodos , Ombligo , Adulto JovenRESUMEN
BACKGROUND: The aim of this study was to evaluate the pharmacokinetics of lamivudine (3TC), stavudine (d4T) and nevirapine (NVP) in HIV-infected Malawian children receiving quartered tablet multiples of Triomune 40 (generic tablet [GT]) compared with individual generic liquid (GL) and trade liquid (TL). METHODS: This was a prospective randomized three-way crossover study. Patients (8-<12 kg, 18-<22 kg or 28-<32 kg body weight) taking Triomune 40 were recruited and randomized to receive GT twice daily (one-quarter, one-half or three-quarter tablets using Malawi treatment guidelines), GL twice daily (in the equivalent dose of GT) or TL twice daily (dosed using weight and age from US Department of Health and Human Services paediatric treatment guidelines). After 10 days of one formulation, 6-h pharmacokinetic sampling was performed, and patients were crossed over to subsequent formulations. Baseline concentration (C(0 h)), area under the curve (AUC)(0-6 h), maximum plasma concentration (C(max)) and time to C(max) were generated for each antiretroviral treatment. RESULTS: A total of 7 males and 11 females (6 in each GT dosing group) with a median (range) age of 7.2 years (1.3-13.6), weight of 19 kg (9.0-30.5) and height of 109 cm (75-132) were recruited. Combining all patients, no difference in pharmacokinetics was noted among the formulations for all drugs. However, patients in the one-quarter GT dosing group (8-<12 kg) had lower 3TC exposures than with the GL or TL (3TC AUC(0-6 h) 1,102, 1,720 and 2,060 h*ng/ml, respectively; P<0.005) and had more subtherapeutic NVP C(0 h) (10 of 13 occasions versus the one-half and three-quarter tablet groups). Compared with Western paediatric cohorts, Malawians had concentrations 30-40% lower for 3TC and d4T and 50% higher for NVP. CONCLUSIONS: Quartered multiples of Triomune 40 are appropriate for children 18-<22 kg and 28-<32 kg in weight; however, alternative formulations are suggested in children weighing 8-<12 kg.
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Fármacos Anti-VIH/farmacocinética , Medicamentos Genéricos/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Lamivudine/farmacocinética , Nevirapina/farmacocinética , Estavudina/farmacocinética , Adolescente , Fármacos Anti-VIH/administración & dosificación , Peso Corporal , Niño , Preescolar , Estudios Cruzados , Formas de Dosificación , Esquema de Medicación , Medicamentos Genéricos/administración & dosificación , Femenino , VIH , Infecciones por VIH/virología , Humanos , Lactante , Lamivudine/administración & dosificación , Malaui , Masculino , Nevirapina/administración & dosificación , Estudios Prospectivos , Estavudina/administración & dosificaciónRESUMEN
STUDY OBJECTIVES: To evaluate whether patients with human immunodeficiency virus (HIV) infection who were receiving protease inhibitor therapy had altered bile acid concentrations compared with noninfected control subjects, and whether bile acid concentrations could predict the onset of hepatotoxicity caused by protease inhibitors. DESIGN: Retrospective sample analysis from a prospectively conducted clinical trial. SETTING: Academic research center. PATIENTS: Eleven adults with advanced HIV disease who were taking protease inhibitor-based antiretroviral therapy, one of whom had developed protease inhibitor-induced hepatotoxicity. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), and taurocholic acid (TC) were analyzed by using a novel high-performance liquid chromatography with tandem mass spectrometry detection method. Comparisons of the relative contribution of each bile acid to the total bile acid pool were made with previously published values and with bile acid concentrations contained in two pooled plasma samples from healthy, non-HIV-infected volunteers analyzed in our laboratory. Each pooled plasma sample used for this analysis contained contributions from three non-HIV-infected volunteers. The LCA and TC concentrations in HIV-infected patients were 3-4-fold higher than those previously reported for non-HIV-infected subjects; concentrations of other bile acids were similar to those of previous reports. The relative contribution of CDCA to the total bile acid pool was 9% in HIV-infected patients compared with 30-50% in noninfected subjects. Total and individual bile acid concentrations in the HIV-infected patient who developed hepatotoxicity were similar to the bile acid concentrations from the other study patients who did not develop hepatotoxicity. CONCLUSION: These data suggest that bile acid concentrations may be altered by HIV infection and/or protease inhibitor therapy. However, further investigations should be performed to assess whether antiretroviral-associated hepatotoxicity can be predicted by alterations in individual bile acid concentrations.
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Ácidos y Sales Biliares/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Infecciones por VIH/sangre , Inhibidores de la Proteasa del VIH/efectos adversos , Hígado/efectos de los fármacos , Adulto , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Ácido Quenodesoxicólico/sangre , Cromatografía Líquida de Alta Presión , Diagnóstico Precoz , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Ácido Litocólico/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Espectrometría de Masas en Tándem , Ácido Taurocólico/sangre , Factores de TiempoRESUMEN
Few studies have examined the psychosocial factors associated with sexual transmission behaviors among HIV-positive men who have sex with men (MSM), heterosexual men (MSW) and women. We enrolled 1,050 sexually active HIV-positive patients at seven HIV clinics in six US cities as part of a clinic-based behavioral intervention. We describe the sexual transmission behaviors and examine demographic, clinical, psychosocial, and clinic prevention variables associated with unprotected anal or vaginal intercourse (UAVI). Twenty-three percent of MSM, 12.3% of MSW and 27.8% of women engaged in UAVI with partners perceived to be HIV-negative or of unknown serostatus. Among MSM and MSW, having multiple partners and lower self-efficacy were associated with increased odds of UAVI. Self-rating one's health status as excellent/very good was a risk factor for UAVI among MSM. Among women, binge drinking and stressful life events were associated with UAVI. These findings identify variables that warrant attention in targeted interventions.
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Infecciones por VIH/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Heterosexualidad/psicología , Homosexualidad Masculina/psicología , Adulto , Demografía , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Heterosexualidad/estadística & datos numéricos , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Parejas Sexuales/psicología , Apoyo Social , Encuestas y Cuestionarios , Estados UnidosRESUMEN
The objective of the study was to measure antiretroviral exposures in four physiological compartments during pregnancy, delivery, and postpartum. This prospective, open-label, longitudinal study collected paired blood plasma (BP) and genital tract (GT) aspirates antepartum, at delivery, and up to 12 weeks postpartum. Antiretroviral cord BP and amniotic fluid concentrations were also measured. Drug concentrations were analyzed by validated high-performance liquid chromatography/UV and liquid chromatography/tandem mass spectrometry methods, with secondary compartment concentrations presented as the percentage of BP. Fourteen women taking lamivudine plus zidovudine and either lopinavir-ritonavir (n = 7), nelfinavir (n = 6), or nevirapine (n = 1) were enrolled; four also received tenofovir. GT penetration relative to BP was highest for the nucleoside reverse transcriptase inhibitors compared to the protease inhibitors and nevirapine. Only antepartum nelfinavir GT penetration was significantly higher than in the second trimester (geometric mean ratio [GMR], 179.3) or third trimester (GMR, 41.9). Compared to nonpregnant historical controls, antepartum GT penetration was significantly lower (P < 0.05) for zidovudine (GMR, 0.25) and lopinavir (GMR, 0.03); postpartum lopinavir GT penetration continued to be significantly lower (GMR, 0.27). Cord BP exposures were highest for lamivudine and tenofovir (> or = 100%), with cord BP levels of the remaining drugs ranging from 49 to 86% of that of the respective BP level. Amniotic exposures for lamivudine, zidovudine, tenofovir, and nelfinavir were > or = 100%, nevirapine exposure was 53%, and lopinavir and ritonavir exposures were < or = 6% that of BP. We conclude that GT, cord BP, and amniotic fluid exposures vary within and between antiretroviral drug classes and biologic sites. Measurement of antiretroviral exposure in maternal genital secretions, cord BP, and amniotic fluid may be needed to identify signals of subtherapeutic or supratherapeutic drug exposure.
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Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Líquido Amniótico/metabolismo , Fármacos Anti-VIH/farmacocinética , Sangre Fetal/metabolismo , Genitales Femeninos/metabolismo , VIH-1 , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Adulto , Citocromo P-450 CYP3A , Sistema Enzimático del Citocromo P-450/biosíntesis , Femenino , Genitales Femeninos/virología , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/orina , Embarazo , ARN Viral/sangreRESUMEN
PURPOSE: The effects of omeprazole on indinavir when administered alone or in combination with ritonavir were evaluated. METHODS: Fourteen men and women age 18-55 years not infected with human immunodeficiency virus who met study qualifications were randomized to receive placebo, 20 mg of omeprazole, or 40 mg of omeprazole daily. After seven days, the single-dose pharmacokinetic profile of an 800-mg dose of indinavir alone or in combination with 200 mg of ritonavir was evaluated. Study participants received each of four study regimens in one of four randomly assigned orders. Blood samples were collected, and plasma indinavir and ritonavir concentrations were analyzed using high-performance liquid chromatography. RESULTS: The coadministration of 20 or 40 mg of omeprazole with indinavir significantly reduced the mean indinavir area under the concentration-versus-time curve (AUC) from 30.0 mg x hr/L (95% confidence interval [CI], 21.9-41.1 mg x hr/L) to 19.7 mg x hr/L (95% CI, 14.6-26.8 mg x hr/L) or 16.0 mg x hr/L (95% CI, 11.8-21.7 mg x hr/L), respectively (p < 0.002). The addition of 200 mg of ritonavir to 800 mg of indinavir in combination with 40 mg of omeprazole significantly increased the mean indinavir AUC from 30.0 mg x hr/L (95% CI, 21.9-41.1 mg x hr/L) to 46.6 mg x hr/L (95% CI, 34.0-63.8 mg x hr/L), but it did not significantly affect mean omeprazole concentrations (p < or = 0.02). CONCLUSION: The AUC of indinavir was substantially decreased in healthy volunteers who received omeprazole 20 or 40 mg daily for seven days before the administration of a single 800-mg dose of indinavir. Concomitant administration of ritonavir 200 mg with indinavir in participants receiving omeprazole led to a significant increase in the AUC of indinavir.
Asunto(s)
Antiulcerosos/farmacología , Inhibidores de la Proteasa del VIH/farmacocinética , Indinavir/farmacocinética , Omeprazol/farmacología , Ritonavir/farmacología , Adolescente , Adulto , Antiulcerosos/administración & dosificación , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Inhibidores de la Proteasa del VIH/farmacología , Humanos , Masculino , Persona de Mediana Edad , Omeprazol/administración & dosificaciónRESUMEN
Previous investigations have shown a significant negative two-way drug interaction between fosamprenavir (FPV) and lopinavir/ritonavir (LPV/RTV) in both human immunodeficiency virus (HIV)-infected patients and seronegative volunteers. This randomized, nonblinded, three-way crossover study of HIV-seronegative adult volunteers investigated dose separation and increased doses of RTV as a means to overcome the interaction between FPV and LPV/RTV. Eleven HIV-seronegative volunteers were given FPV plus LPV/RTV at 700 mg plus 400/100 mg every 12 hours (q12h) simultaneously for 10 days and then randomized to receive each of three 7-day treatments in one of six possible sequences, as follows: FPV plus LPV/RTV at 700 mg plus 400 mg/100 mg q12h simultaneously, FPV/RTV at 700 mg/100 mg q12h plus LPV/RTV at 400 mg/100 mg q12h, with doses separated by 4 h, and FPV/RTV at 1,400 mg/200 mg in the morning plus LPV/RTV at 800 mg/200 mg in the evening. Pharmacokinetic sampling was performed on day 8 of each treatment, and samples were analyzed for FPV, amprenavir (APV), LPV, and RTV concentrations by high-performance liquid chromatography-tandem mass spectrometry. Geometric mean ratios (GMR [with 95% confidence intervals]) for the 4- and 12-h dose separation strategies compared to simultaneous administration were calculated for the areas under the concentration-time curves from 0 to 24 h. Compared to simultaneous administration, RTV exposures increased with both 4-h and 12-h dose separation strategies (GMR, 5.30 [3.66 to 7.67] and 4.45 [3.09 to 6.41], respectively). LPV exposures also significantly increased with both 4-h and 12-h dose separation strategies (GMR, 1.76 [1.34 to 2.32] and 1.43 [1.02 to 2.01], respectively). However, both the 4- and 12-h strategies resulted in greater reductions in APV exposure (0.67 [0.54 to 0.83] and 0.77 [0.59 to 0.99], respectively) compared to simultaneous administration. Additional investigations are warranted to determine the optimal dosing of FPV with LPV/RTV.
Asunto(s)
Carbamatos/farmacocinética , Inhibidores de la Proteasa del VIH/farmacocinética , Organofosfatos/farmacocinética , Pirimidinonas/farmacocinética , Ritonavir/farmacocinética , Sulfonamidas/farmacocinética , Adolescente , Adulto , Área Bajo la Curva , Carbamatos/administración & dosificación , Carbamatos/sangre , Ensayos Clínicos como Asunto , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Femenino , Furanos , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/sangre , Seronegatividad para VIH , Humanos , Lopinavir , Masculino , Organofosfatos/administración & dosificación , Organofosfatos/sangre , Pirimidinonas/administración & dosificación , Pirimidinonas/sangre , Ritonavir/administración & dosificación , Ritonavir/sangre , Sulfonamidas/administración & dosificación , Sulfonamidas/sangreRESUMEN
RATIONALE AND PURPOSE: Motivational interviewing (MI) is a counseling technique that has been used effectively to change a number of health-related behaviors. We sought to assess the impact on patients' antiretroviral therapy (ART) adherence of a multicomponent, MI-based ART adherence intervention compared with that of an HIV informational control program. STUDY DESIGN: Two-arm, randomized, controlled trial. SAMPLE: One hundred forty adult HIV-infected patients attending a large, academic center infectious diseases clinic who were either failing or newly initiating an ART regimen. STUDY ENDPOINTS: (1) Mean adherence level (% of prescribed doses take in the prior month) at the week 12 visit, (2) change in mean adherence, (3) percentage of patients achieving >95% adherence in the third 4-week block, and (4) change in viral load. MAIN FINDINGS: The MI group's mean adherence improved by 4.5% compared with a decrease in the control group's adherence by 3.83% (P = 0.10). In the treatment group, 29% achieved >95% adherence compared with only 17% in the control group (P = 0.13). When we controlled for ethnicity, the intervention group had 2.75 times higher odds of achieving more than 95% adherence than did the controls (P = 0.045; 95% confidence interval: 1.023, 7.398). Although a number of mediating variables (beliefs about ART, coping style, social support, and goals set) had statistically significant changes in the expected direction in the MI group compared with controls, in the intent-to-treat analysis, the mean adherence at study exit for the intervention group was 76% (SD = 27%) and 71% (SD = 27%) for the control group (P = 0.62). CONCLUSION: Although not definitive, this study provides some evidence that MI offers an effective approach to improving adherence. Future studies able to build MI into the intervention for longer than 3 months may have a greater impact.