RESUMEN
CYP2C19 genotype has been shown to impact response to clopidogrel 75-mg but not prasugrel 10-mg. Here, we assessed effects of CYP2C19 metaboliser status on pharmacokinetics (PK) and pharmacodynamic (PD) responses to prasugrel 5-mg and 10-mg and clopidogrel 75-mg using data from two PK/PD studies in stable coronary artery disease (CAD) patients (GENERATIONS and FEATHER). Active metabolite concentrations (area under the curve, AUC[0-tlast]), maximum platelet aggregation (MPA) measured by light transmission aggregometry, vasodilator-stimulated phosphoprotein platelet reactivity index, and VerifyNow P2Y12-platelet reaction units (VN-PRU) were analysed by CYP2C19-predicted phenotype (extensive metaboliser [EM; N=154], *2-*8 non-carriers, vs reduced metaboliser [RM; N=41],*2-*8 carriers/*17 non-carriers). AUC(0-tlast) was unaffected by metaboliser status for prasugrel 5-mg and 10-mg (geometric mean EM/RM ratios 1.00, 95% confidence interval [CI]: 0.86,1.17, p>0.99; and 0.97, 95% CI:0.85,1.12, p=0.71, respectively), but was lower among RMs receiving clopidogrel 75-mg (1.37, 95% CI:1.14,1.65, p<0.001). Platelet reactivity was not significantly affected by CYP2C19 metaboliser status for prasugrel 5-mg, or for prasugrel 10-mg by MPA and VN-PRU, but for clopidogrel 75-mg was significantly higher in reduced metabolisers (all measures p<0.01). Prasugrel 10-mg showed greater antiplatelet effects vs clopidogrel 75-mg (all comparisons p<0.001). Prasugrel 5-mg showed greater antiplatelet effects vs clopidogrel 75-mg in RMs (all p<0.001), and comparable effects in EMs (all p≥0.37). In contrast to clopidogrel, prasugrel active metabolite PK was not influenced by CYP2C19 genotype. Antiplatelet effect for prasugrel 10-mg was greater irrespective of metaboliser status and for prasugrel 5-mg was greater for RMs and comparable for EMs as compared to clopidogrel 75-mg.
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Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Citocromo P-450 CYP2C19/genética , Piperazinas/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Tiofenos/farmacocinética , Ticlopidina/análogos & derivados , Anciano , Protocolos Clínicos , Clopidogrel , Enfermedad de la Arteria Coronaria/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Piperazinas/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/genética , Inhibidores de Agregación Plaquetaria/administración & dosificación , Polimorfismo Genético , Clorhidrato de Prasugrel , Tiofenos/administración & dosificación , Ticlopidina/administración & dosificación , Ticlopidina/farmacocinética , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Prasugrel is a thienopyridine antiplatelet agent under investigation for the prevention of atherothrombotic events in patients with acute coronary syndrome who undergo percutaneous coronary intervention. Patients with chronic liver disease are among those in the target population for prasugrel. As hepatic enzymes play a key role in formation of prasugrel's active metabolite, hepatic impairment could affect the safety and/or efficacy of prasugrel in such patients. METHODS: This was a parallel-design, open-label, multiple dose study of 30 subjects, 10 with moderate hepatic impairment (Child-Pugh Class B) and 20 with normal hepatic function. Prasugrel was administered orally as a 60-mg loading dose (LD) and daily 10-mg maintenance doses (MDs) for 5 days. Pharmacokinetic parameters (AUC(0-t), C(max) and t(max)) and maximal platelet aggregation (MPA) by light transmission aggregometry were assessed after the LD and final MD. RESULTS AND DISCUSSION: Exposure to prasugrel's active metabolite was comparable between healthy subjects and those with moderate hepatic impairment. Point estimates for the ratios of geometric least square means for AUC(0-t) and C(max) after the LD and last MD ranged from 0.91 to 1.14. MPA to 20 microm ADP was similar between subjects with moderate hepatic impairment and healthy subjects for both the LD and MD. Prasugrel was well tolerated by all subjects, and adverse events were mild in severity. CONCLUSION: Moderate hepatic impairment appears to have no effect on exposure to prasugrel's active metabolite. Furthermore, MPA results suggest that moderate hepatic impairment has little or no effect on platelet aggregation relative to healthy controls. Overall, these results suggest that a dose adjustment would not be required in moderately hepatically impaired patients taking prasugrel.
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Hepatopatías/metabolismo , Piperazinas/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Tiofenos/farmacocinética , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/efectos adversos , Piperazinas/farmacología , Clorhidrato de Prasugrel , Tiofenos/efectos adversos , Tiofenos/farmacologíaRESUMEN
OBJECTIVE: The pharmacokinetic (PK) and pharmacodynamic (PD) responses to prasugrel were compared in three studies of healthy subjects vs. those with moderate or end-stage renal impairment. METHODS: Two of the three protocols were parallel-design, open-label, single dose (60-mg prasugrel) studies in subjects with end-stage renal disease (ESRD; n = 12) or moderate renal impairment (n = 10) and matched healthy subjects with normal renal function (n = 10). The third protocol was an open-label, single-dose escalation (5, 10, 30 and 60 mg prasugrel) study in subjects with ESRD (n = 16) and matched healthy subjects with normal renal function (n = 16). Plasma concentrations of prasugrel's active metabolite were determined and pharmacokinetic parameter estimates were derived. Maximum platelet aggregation (MPA) was measured by light transmission aggregometry using 20 mum adenosine diphosphate as agonist. RESULTS: Across all studies, prasugrel's C(max) and AUC(0-t) were 51% and 42% lower in subjects with ESRD than in healthy subjects. AUC(0-t) did not differ between healthy subjects and subjects with moderate renal impairment. The magnitude of change and time-course profiles of MPA was similar for healthy subjects compared with subjects with moderate renal impairment and those with ESRD. Prasugrel was well-tolerated in all subjects. CONCLUSION: There was no difference in pharmacokinetics or PD responses between subjects with moderate renal impairment and healthy subjects. Despite significantly lower exposure to prasugrel's active metabolite in subjects with ESRD, MPA did not differ between healthy subjects and those with ESRD.
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Enfermedades Renales/metabolismo , Fallo Renal Crónico/metabolismo , Piperazinas/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Tiofenos/farmacocinética , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/efectos adversos , Piperazinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Clorhidrato de Prasugrel , Unión Proteica , Tiofenos/efectos adversos , Tiofenos/farmacologíaRESUMEN
OBJECTIVE: Prasugrel is a thienopyridine antiplatelet agent for the prevention of atherothrombotic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Since cytochrome P450 enzymes CYP3A4 and CYP2B6 play a major role in prasugrel's active metabolite formation, the effect of potent CYP induction by rifampin on the pharmacokinetics of prasugrel and on the pharmacodynamic response to prasugrel was evaluated in healthy male subjects. RESEARCH DESIGN AND METHODS: This was an open-label, two-period, fixed-sequence study conducted at a single clinical research center. In the first treatment period, subjects received prasugrel as an oral 60-mg loading dose (LD) on the first day followed by ten oral, 10-mg daily maintenance doses. After a 2-week washout period, subjects received oral rifampin alone (600 mg once daily) for 8 days, followed by coadministration of oral rifampin with prasugrel, given as a 60-mg LD on the first day followed by five daily 10-mg MDs. Blood collection for pharmacokinetic and pharmacodynamic analyses occurred after the LD and fifth MD of prasugrel in both periods. CLINICAL TRIAL SYNOPSIS: clinicalstudyresults.org ID #8976 RESULTS: Rifampin coadministration (600 mg daily) did not affect exposure to prasugrel's active metabolite (R-138727). However, at 2 and 4 h after the prasugrel loading dose (60 mg), rifampicin coadministration was associated with a 6-9 percentage point decrease (p < 0.01) in the magnitude of platelet inhibition; similarly, a 5-17 percentage point decrease (p < 0.05) was observed with rifampin coadministration during the prasugrel maintenance dose (10 mg) period. Post hoc in vitro experiments demonstrated a dose-dependent R-138727-rifampin interaction at the P2Y(12) level unrelated to enzyme induction. A limitation of this study is that while results of the in vitro post hoc study indicate a pharmacodynamic interaction with rifampin, the mechanism underlying this interaction has not been elucidated. CONCLUSIONS: Dose adjustment should not be necessary when prasugrel is administered with CYP inducers since formation of prasugrel's active metabolite is not affected by potent enzyme induction with rifampin.
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Antibióticos Antituberculosos/farmacología , Piperazinas/farmacología , Piperazinas/farmacocinética , Rifampin/farmacología , Tiofenos/farmacología , Tiofenos/farmacocinética , Síndrome Coronario Agudo , Adolescente , Adulto , Antibióticos Antituberculosos/administración & dosificación , Interacciones Farmacológicas , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Clorhidrato de Prasugrel , Rifampin/administración & dosificación , Tiofenos/administración & dosificación , Adulto JovenRESUMEN
Many nearshore fish and invertebrate populations are overexploited even when apparently coherent management structures are in place. One potential cause of mismanagement may be a poor understanding and accounting of stochasticity, particularly for stock recruitment. Many of the fishes and invertebrates that comprise nearshore fisheries are relatively sedentary as adults but have an obligate larval pelagic stage that is dispersed by ocean currents. Here, we demonstrate that larval connectivity is inherently an intermittent and heterogeneous process on annual time scales. This stochasticity arises from the advection of pelagic larvae by chaotic coastal circulations. This result departs from typical assumptions where larvae simply diffuse from one site to another or where complex connectivity patterns are created by transport within spatially complicated environments. We derive a statistical model for the expected variability in larval settlement patterns and demonstrate how larval connectivity varies as a function of different biological and physical processes. The stochastic nature of larval connectivity creates an unavoidable uncertainty in the assessment of fish recruitment and the resulting forecasts of sustainable yields.
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Peces/crecimiento & desarrollo , Invertebrados/crecimiento & desarrollo , Animales , Larva/crecimiento & desarrollo , Larva/fisiología , Estadios del Ciclo de Vida , Modelos Biológicos , Océanos y Mares , Procesos Estocásticos , Factores de TiempoRESUMEN
BACKGROUND: Little is known about the prevalence or correlates of DSM-IV pathological gambling (PG). METHOD: Data from the US National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey, were used to assess lifetime gambling symptoms and PG along with other DSM-IV disorders. Age of onset (AOO) of each lifetime disorder was assessed retrospectively. AOO reports were used to study associations between temporally primary disorders and the subsequent risk of secondary disorders. RESULTS: Most respondents (78.4%) reported lifetime gambling. Lifetime problem gambling (at least one Criterion A symptom of PG) (2.3%) and PG (0.6%) were much less common. PG was significantly associated with being young, male, and Non-Hispanic Black. People with PG reported first gambling significantly earlier than non-problem gamblers (mean age 16.7 v. 23.9 years, z=12.7, p<0.001), with gambling problems typically beginning during the mid-20s and persisting for an average of 9.4 years. During this time the largest annual gambling losses averaged US$4800. Onset and persistence of PG were predicted by a variety of prior DSM-IV anxiety, mood, impulse-control and substance use disorders. PG also predicted the subsequent onset of generalized anxiety disorder, post-traumatic stress disorder (PTSD) and substance dependence. Although none of the NCS-R respondents with PG ever received treatment for gambling problems, 49.0% were treated at some time for other mental disorders. CONCLUSIONS: DSM-IV PG is a comparatively rare, seriously impairing, and undertreated disorder whose symptoms typically start during early adulthood and is frequently secondary to other mental or substance disorders that are associated with both PG onset and persistence.
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Recolección de Datos/métodos , Recolección de Datos/estadística & datos numéricos , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos Disruptivos, del Control de Impulso y de la Conducta/epidemiología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/psicología , Juego de Azar/psicología , Adolescente , Adulto , Distribución por Edad , Edad de Inicio , Comorbilidad , Trastornos Disruptivos, del Control de Impulso y de la Conducta/diagnóstico , Etnicidad , Femenino , Humanos , Masculino , Trastornos Mentales/epidemiología , Trastornos Mentales/psicología , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prevalencia , Estudios Retrospectivos , Distribución por Sexo , Factores Socioeconómicos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Prasugrel is a novel antiplatelet prodrug of the same thienopyridine class as clopidogrel and ticlopidine. Metabolism of prasugrel generates the active metabolite R-138727, an antagonist of the platelet P2Y(12) adenosine diphosphate (ADP) receptor, leading to inhibition of ADP-mediated platelet activation and aggregation. ADP also enhances the platelet response to collagen, and these two agonists contribute to the generation of platelet procoagulant activity. We therefore examined whether R-138727 inhibits ADP- and collagen-triggered platelet procoagulant activities. METHODS AND RESULTS: As shown by whole blood flow cytometry, R-138727 inhibited surface phosphatidylserine expression on ADP plus collagen-stimulated platelets and tissue factor (TF) expression on ADP-, collagen-, and ADP plus collagen-stimulated monocyte-platelet aggregates. R-138727 reduced monocyte-platelet aggregate formation, thereby further inhibiting TF expression. ADP, collagen, and ADP plus collagen accelerated the kinetics of thrombin generation in recalcified whole blood and R-138727 significantly inhibited this acceleration. Clot strength in a modified thromboelastograph system was also inhibited by R-138727 (IC50 0.7 +/- 0.1 microM). CONCLUSIONS: In addition to its previously known inhibitory effects on platelet activation and aggregation, the active metabolite of prasugrel, R-138727, inhibits platelet procoagulant activity in whole blood (as determined by phosphatidylserine expression on platelets and TF expression on monocyte-platelet aggregates), resulting in the functional consequences of delayed thrombin generation and impaired clot development.
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Factores de Coagulación Sanguínea/antagonistas & inhibidores , Plaquetas/efectos de los fármacos , Retracción del Coagulo/efectos de los fármacos , Piperazinas/farmacología , Piperazinas/farmacocinética , Activación Plaquetaria/efectos de los fármacos , Profármacos/farmacocinética , Antagonistas del Receptor Purinérgico P2 , Tiofenos/farmacocinética , Adenosina Difosfato/farmacología , Anexina A5/metabolismo , Biotransformación , Colágeno/farmacología , Humanos , Monocitos/metabolismo , Fosfatidilserinas/sangre , Clorhidrato de Prasugrel , Receptores Purinérgicos P2Y12 , Tromboelastografía , Trombina/biosíntesis , Tromboplastina/biosíntesisRESUMEN
BACKGROUND: Thienopyridines are metabolized to active metabolites that irreversibly inhibit the platelet P2Y(12) adenosine diphosphate receptor. The pharmacodynamic response to clopidogrel is more variable than the response to prasugrel, but the reasons for variation in response to clopidogrel are not well characterized. OBJECTIVE: To determine the relationship between genetic variation in cytochrome P450 (CYP) isoenzymes and the pharmacokinetic/pharmacodynamic response to prasugrel and clopidogrel. METHODS: Genotyping was performed for CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP3A4 and CYP3A5 on samples from healthy subjects participating in studies evaluating pharmacokinetic and pharmacodynamic responses to prasugrel (60 mg, n = 71) or clopidogrel (300 mg, n = 74). RESULTS: In subjects receiving clopidogrel, the presence of the CYP2C19*2 loss of function variant was significantly associated with lower exposure to clopidogrel active metabolite, as measured by the area under the concentration curve (AUC(0-24); P = 0.004) and maximal plasma concentration (C(max); P = 0.020), lower inhibition of platelet aggregation at 4 h (P = 0.003) and poor-responder status (P = 0.030). Similarly, CYP2C9 loss of function variants were significantly associated with lower AUC(0-24) (P = 0.043), lower C(max) (P = 0.006), lower IPA (P = 0.046) and poor-responder status (P = 0.024). For prasugrel, there was no relationship observed between CYP2C19 or CYP2C9 loss of function genotypes and exposure to the active metabolite of prasugrel or pharmacodynamic response. CONCLUSIONS: The common loss of function polymorphisms of CYP2C19 and CYP2C9 are associated with decreased exposure to the active metabolite of clopidogrel but not prasugrel. Decreased exposure to its active metabolite is associated with a diminished pharmacodynamic response to clopidogrel.
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Hidrocarburo de Aril Hidroxilasas/metabolismo , Plaquetas/efectos de los fármacos , Oxigenasas de Función Mixta/metabolismo , Piperazinas/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Polimorfismo Genético , Profármacos/farmacología , Tiofenos/farmacología , Ticlopidina/análogos & derivados , Adulto , Área Bajo la Curva , Hidrocarburo de Aril Hidroxilasas/genética , Plaquetas/metabolismo , Ensayos Clínicos como Asunto , Clopidogrel , Estudios Cruzados , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C9 , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta/genética , Fenotipo , Piperazinas/sangre , Piperazinas/farmacocinética , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/sangre , Inhibidores de Agregación Plaquetaria/farmacocinética , Clorhidrato de Prasugrel , Profármacos/farmacocinética , Antagonistas del Receptor Purinérgico P2 , Receptores Purinérgicos P2/metabolismo , Receptores Purinérgicos P2Y12 , Valores de Referencia , Proyectos de Investigación , Estudios Retrospectivos , Tiofenos/sangre , Tiofenos/farmacocinética , Ticlopidina/sangre , Ticlopidina/farmacocinética , Ticlopidina/farmacologíaRESUMEN
Health initiatives suggest that adolescent substance use assessment may be beneficial as part of primary care to screen for early problematic behaviors. To examine the accuracy of such reporting, we compared the anonymous and confidential self-reports of 180 adolescents in a primary care setting. Matching samples to control for demographic variables, we found that adolescents were more likely to report marijuana use and substance use behaviors, such as selling drugs, when reporting anonymously vs. reporting confidentially. These results challenge the accuracy of confidential self-reports within this setting, and suggest further research is needed.
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Tamizaje Masivo , Trastornos Mentales/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Pruebas Anónimas , Comorbilidad , Confidencialidad , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Abuso de Marihuana/diagnóstico , Abuso de Marihuana/epidemiología , Abuso de Marihuana/psicología , Trastornos Mentales/diagnóstico , Trastornos Mentales/psicología , North Carolina , Atención Primaria de Salud , Autorrevelación , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
Prasugrel and clopidogrel inhibit platelet aggregation through active metabolite formation. Prasugrel's active metabolite (R-138727) is formed primarily by cytochrome P450 (CYP) 3A and CYP2B6, with roles for CYP2C9 and CYP2C19. Clopidogrel's activation involves two sequential steps by CYP3A, CYP1A2, CYP2C9, CYP2C19, and/or CYP2B6. In a randomized crossover study, healthy subjects received a loading dose (LD) of prasugrel (60 mg) or clopidogrel (300 mg), followed by five daily maintenance doses (MDs) (15 and 75 mg, respectively) with or without the potent CYP3A inhibitor ketoconazole (400 mg/day). Subjects had a 2-week washout between periods. Ketoconazole decreased R-138727 and clopidogrel active metabolite Cmax (maximum plasma concentration) 34-61% after prasugrel and clopidogrel dosing. Ketoconazole did not affect R-138727 exposure or prasugrel's inhibition of platelet aggregation (IPA). Ketoconazole decreased clopidogrel's active metabolite AUC0-24 (area under the concentration-time curve to 24 h postdose) 22% (LD) to 29% (MD) and reduced IPA 28% (LD) to 33% (MD). We conclude that CYP3A4 and CYP3A5 inhibition by ketoconazole affects formation of clopidogrel's but not prasugrel's active metabolite. The decreased formation of clopidogrel's active metabolite is associated with reduced IPA.
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Inhibidores del Citocromo P-450 CYP3A , Inhibidores Enzimáticos/farmacología , Cetoconazol/farmacología , Piperazinas/farmacocinética , Inhibidores de Agregación Plaquetaria/farmacocinética , Tiofenos/farmacocinética , Ticlopidina/análogos & derivados , Adulto , Área Bajo la Curva , Clopidogrel , Estudios Cruzados , Método Doble Ciego , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/administración & dosificación , Piperazinas/farmacología , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacología , Clorhidrato de Prasugrel , Tiofenos/administración & dosificación , Tiofenos/farmacología , Ticlopidina/administración & dosificación , Ticlopidina/farmacocinética , Ticlopidina/farmacologíaRESUMEN
Clinicians working with adolescents are routinely faced with the issue that alcohol and other drug (AOD) involvement may be part of the clinical picture either as a primary problem or a contributing factor to other problems or disorders. Fortunately, assessment research in this area has produced several behaviorally oriented and psychometrically sound tools from which to choose for problem identification, referral and treatment of youth suspected of AOD abuse. The aim of this paper is to provide an overview of several issues related to the clinical utility of such assessment tools.
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Alcoholismo/diagnóstico , Trastornos Relacionados con Opioides/diagnóstico , Adolescente , Humanos , Psicometría , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosAsunto(s)
Ética , Juego de Azar/psicología , Política Pública , Humanos , Medios de Comunicación de Masas , Opinión Pública , Estados UnidosRESUMEN
OBJECTIVE: To improve assessment of the DSM-IV alcohol tolerance criterion in adolescents, this study tested the performance of a minimum percentage increase in drinking quantity, and a proxy measure of tolerance (i.e., average heavy-drinking quantity per occasion) in identifying adolescents with alcohol dependence. METHOD: Two adolescent samples were examined. In one sample (N = 415, 58% male, 79% white, 57% clinical), a modified version of the SCID was used to determine DSM-IV alcohol diagnoses, and lifetime drinking history data were collected by interview. In the second sample (N = 470, 60% male, 76% white, 100% clinical), the Adolescent Diagnostic Interview was used to determine DSM-IV alcohol diagnoses and to collect data on initial- and current-drinking quantities needed to become intoxicated. The performance of a percentage increase and average heavy-drinking quantity in identifying those with dependence was evaluated using receiver operating characteristic analysis. RESULTS: The utility of a percentage increase definition was limited by the high degree of variability in initial-drinking quantities. Percentage increase may underassign the tolerance symptom when initial-drinking quantities are high and overassign the symptom when initial-drinking quantities are low. Average heavy-drinking quantity per occasion, combined with a minimum frequency of drinking, demonstrated better performance than any percentage increase definition. CONCLUSIONS: Alternatives to a change-based (e.g., percentage increase) definition of tolerance warrant study due to limits of change-based definitions when initial-drinking quantity shows a high degree of variability. The variability in initial-drinking quantity may reflect individual differences in initial sensitivity that need to be considered in tolerance assessment.
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Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Etanol , Adolescente , Tolerancia a Medicamentos , Femenino , Humanos , Masculino , Prevalencia , Escalas de Valoración PsiquiátricaRESUMEN
This study measured the outcome of four state-supported outpatient gambling treatment programs in Minnesota. The programs were developed specifically for the treatment of pathological gamblers and offered multiple modalities of treatment including individual, group, education, twelve-step work, family groups, and financial counseling. The therapeutic orientation was eclectic with an emphasis on the twelve steps of Gamblers Anonymous (GA) and a treatment goal of abstinence. The sample included 348 men and 220 women treated between January 1992 and January 1995. A pretest-posttest design was utilized with multidimensional assessments obtained at intake, discharge, six-months, and twelve-months post-discharge. Variables assessed included a range of clinical and outcome variables. At six month follow-up, 28% reported that they had abstained from gambling during the six months following discharge and an additional 20% had gambled less than once per month. Almost half of the sample (48%) showed clinically significant improvement in gambling frequency at six month follow-up. Outcome variables of gambling frequency, SOGS scores, amount of money gambled, number of friends who gamble, psychosocial problems, and number of financial problems, all showed statistically significant improvements from pretreatment to follow-up. The treatment programs yielded outcome results similar to those reported for alcohol and drug abuse treatment programs.
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Trastornos Disruptivos, del Control de Impulso y de la Conducta/psicología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/terapia , Juego de Azar/psicología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Programas y Proyectos de Salud , Resultado del TratamientoRESUMEN
We studied the effects of a 6-month withdrawal of exercise after 12 months of progressive impact (jump) plus lower body resistance training on risk factors for hip fracture in premenopausal women (age, 30-45 years). Twenty-nine women completed the 12-month training and detraining programs and were compared with 22 matched controls. Bone mineral density (BMD) at the greater trochanter, femoral neck, lumbar spine, and whole body and body composition (% body fat) were measured by dual energy X-ray absorptiometry (DXA; Hologic QDR-1000/W). Knee extensor and hip abductor strength were assessed via isokinetic dynamometry (Kin-Com 500H); maximum leg power was tested using a Wingate Anaerobic Power test; and dynamic postural stability was measured on a stabilimeter (Biodex). All measurements were conducted at baseline, 12 months and 18 months with an additional midtraining measurement of BMD. Exercisers trained three times per week in a program of 100 jumps and 100 repetitions of resistance exercises at each session. Intensity was increased using weighted vests to final values of 10% and 13% of body weight (BW) for jump and resistance exercises, respectively. Differences between groups from training were analyzed by repeated measures analysis of covariance (ANCOVA), adjusted for baseline values. Detraining effects were analyzed by comparing the changes from training with the changes from detraining using repeated measures analysis of variance (ANOVA). Baseline values were not significantly different between exercisers and controls. Percent change over the training period was significantly greater in the exercise group than in the control group at the greater trochanter (2.7 +/- 2.5% vs. 0.8 +/- 0.8%, respectively; p < 0.01) and approached significance at the femoral neck (1.2 +/- 3.2% vs. -0.3 +/- 1.9%, respectively; p = 0.06). Significant improvements also were observed in exercisers versus controls for strength and power with exercisers increasing 13-15% above controls, whereas stability was not different between groups. After 6 months of detraining, BMD and muscle strength and power decreased significantly toward baseline values, whereas control values did not change. We conclude that the positive benefits of impact plus resistance training on the musculoskeletal system in premenopausal women reverse when training is withdrawn. Therefore, continued training, perhaps at a reduced frequency and intensity, is required to maintain the musculoskeletal benefit from exercise that may lower fracture risk in later life.
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Densidad Ósea , Ejercicio Físico , Osteoporosis Posmenopáusica/prevención & control , Premenopausia , Adulto , Composición Corporal , Femenino , Humanos , Persona de Mediana Edad , Contracción Muscular , Resistencia a la TracciónRESUMEN
Low bone mineral density (BMD) and poor stability both contribute to increased risk of fractures associated with a fall. Our aim in this cross-sectional study was to determine the anthropometric and/or performance variables that best predicted BMD and stability in women. BMD, body composition, muscle strength, muscle power, and dynamic stability were evaluated in 61 women (age 40 +/- 4 years; % body fat 27% +/- 5%). In correlation analyses, BMD at all sites was significantly related to height, lean mass, strength, and leg power (r2 = 0.25-0.49). Significant inverse relationships were found between all independent variables and dynamic stability (r2 = 0.23-0.52). In stepwise regression, lean mass independently predicted BMD at the femoral neck (R2 = 0.20), total hip (R2 = 0.24), and whole body (R2 = 0.17), whereas hip abductor torque predicted 23% of the variance in trochanter BMD and added 6% to the variance in total hip BMD. Leg power was the only predictor of spine BMD (R2 = 0.14). Fat and lean mass both independently predicted poor performance on postural stability, with fat mass contributing 31% of the total variance (R2 = 0.38). In conclusion, we found lean mass to be a robust predictor of BMD in premenopausal women. Furthermore, both hip abductor torque and leg power independently predicted BMD at clinically relevant fracture sites (hip and spine). The finding that higher fat mass contributes to the majority of the variance in poor stability indicates that greater fat mass may compromise stability and, thus, increase fall risk in heavier individuals.
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Composición Corporal , Densidad Ósea/fisiología , Equilibrio Postural/fisiología , Premenopausia , Absorciometría de Fotón , Adulto , Antropometría , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Músculo Esquelético/fisiología , Valor Predictivo de las Pruebas , Análisis de RegresiónRESUMEN
BACKGROUND: Bone mineral density (BMD) is a primary risk factor for hip fracture. We studied the effect of long-term weighted vest plus jumping exercise on hip BMD in postmenopausal women as a strategy for reducing hip fracture risk. METHODS: Eighteen postmenopausal women (age = 64.1 +/- 1.6 years at baseline, 69.9 +/- 1.6 years at post-testing) who had participated in a 9-month exercise intervention volunteered for the long-term trial. Nine of the original group engaged in weighted vest plus jumping exercise three times per week for 32 weeks of the year over a period of 5 years. Nine of the original controls were active but not enrolled in the exercise program. BMD of the proximal femur was assessed by dual energy x-ray absorptiometry at baseline and after 5 years. RESULTS: At baseline, groups were similar for age, weight, height, years past menopause, and BMD of the femoral neck, trochanter, and total hip. At follow-up, differences in BMD at all regions of the hip were higher in exercisers than controls. For exercisers, changes in BMD were + 1.54% +/- 2.37%, -0.24% +/- 1.02%, and -0.82% +/- 1.04% (means + SE) at the femoral neck, trochanter, and total hip, respectively; controls decreased at all sites (-4.43% +/- 0.93%. 3.43% +/- 1.09%, and -3.80% +/- 1.03%, respectively). CONCLUSIONS: A 5-year program of weighted vest plus jumping exercise maintains hip BMD by preventing significant bone loss in older postmenopausal women. Furthermore, this particular program appears to promote long-term adherence and compliance, as evidenced by the commitment of the exercisers for more than 5 years.
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Terapia por Ejercicio , Articulación de la Cadera/fisiopatología , Artropatías/prevención & control , Osteoporosis Posmenopáusica/prevención & control , Levantamiento de Peso/fisiología , Absorciometría de Fotón , Factores de Edad , Anciano , Análisis de Varianza , Peso Corporal , Densidad Ósea , Femenino , Fémur/fisiología , Cuello Femoral/fisiopatología , Estudios de Seguimiento , Fracturas de Cadera/etiología , Fracturas de Cadera/prevención & control , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Cooperación del Paciente , Posmenopausia/fisiología , Factores de Riesgo , Soporte de Peso/fisiologíaRESUMEN
A structural equation model incorporating substance abuse problem severity, psychosocial risk and protection, and treatment variables examined adolescent drug abuse treatment outcome pathways across 6- and 12-month follow-up points. Findings on resiliency factors and an empirical method adapted from previous research were used to select and assign 10 psychosocial factors to either a multiple protective factor index or a risk factor index. Gender, substance abuse problem severity, treatment modality, treatment length, and aftercare participation were also examined as outcome predictors. The findings suggest that treatment intensity decisions may be better informed by pretreatment psychosocial risk level rather than by substance abuse problem severity. The present study also suggests that drug-abusing adolescents who receive sufficiently long treatment, participate in aftercare, and possess at least 1 individual or interpersonal protective factor during their recovery process have the best chance to maintain gains made during treatment.
Asunto(s)
Psicoterapia/métodos , Tratamiento Domiciliario/métodos , Trastornos Relacionados con Sustancias/psicología , Trastornos Relacionados con Sustancias/terapia , Adolescente , Alcohólicos Anónimos , Alcoholismo/psicología , Alcoholismo/terapia , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Abuso de Marihuana/psicología , Abuso de Marihuana/terapia , Minnesota , Pacientes Ambulatorios/estadística & datos numéricos , Escalas de Valoración Psiquiátrica , Recurrencia , Tratamiento Domiciliario/estadística & datos numéricos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Ajuste Social , Centros de Tratamiento de Abuso de Sustancias/estadística & datos numéricos , Resultado del TratamientoRESUMEN
AIMS: The treatment outcome of drug-abusing adolescents treated with a 12-Step approach. DESIGN: The study compares drug use outcome data at 6 and 12 months post-treatment among three groups of adolescents: those who completed treatment, those who did not and those on a waiting list. Also, among treatment completers, residential and outpatient samples were compared on outcome. SETTING: The treatment site is located in the Minneapolis/St Paul area of Minnesota. PARTICIPANTS: Two hundred and forty-five drug clinic-referred adolescents (12-18 years old), all of whom met at least one DSM-III-R substance dependence disorder. One hundred and seventy-nine subjects received either complete or incomplete 12-Step, Minnesota Model treatment and 66 were waiting list subjects. MEASUREMENTS: In addition to demographics and clinical background variables, measures included treatment involvement, treatment setting and drug use frequency at intake and follow-up. FINDINGS: Absolute and relative outcome analyses indicated that completing treatment was associated with far superior outcome compared to those who did not complete treatment or receive any at all. The percentage of treatment completers who reported either abstinence or a minor lapse for the 12 months following treatment was 53%, compared to 15 and 28% for the incompleter and waiting list groups, respectively. CONCLUSIONS: Favorable treatment outcome for drug abuse was about two to three times more likely if treatment was completed. Also, there were no outcome differences between residential and outpatient groups. Alcohol was the most common drug used during the follow-up period, despite cannabis being the preferred drug at intake.