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Untreated Individuals (untreated + individual)
Selected AbstractsMathematical modelling of the impact of haematopoietic stem cell-delivered gene therapy for HIVTHE JOURNAL OF GENE MEDICINE, Issue 12 2009John M. Murray Abstract Background Gene therapy represents a new treatment paradigm for HIV that is potentially delivered by a safe, once-only therapeutic intervention. Methods Using mathematical modelling, we assessed the possible impact of autologous haematopoietic stem cell (HSC) delivered, anti-HIV gene therapy. The therapy comprises a ribozyme construct (OZ1) directed to a conserved region of HIV-1 delivered by transduced HSC (OZ1+HSC). OZ1+HSC contributes to the CD4+ T lymphocyte and monocyte/macrophage cell pools that preferentially expand under the selective pressure of HIV infection. The model was used to predict the efficacy of OZ1 in a highly active antiretroviral therapy (HAART) naïve individual and a HAART-experienced individual undergoing two structured treatment operations. In the standard scenario, OZ1+HSC was taken as 20% of total body HSC. Results For a HAART-naïve individual, modelling predicts a reduction of HIV RNA at 1 and 2 years post-OZ1 therapy of 0.5 log10 and 1 log10, respectively. Eight years after OZ1 therapy, the CD4+ T-lymphocyte count was 271 cells/mm3 compared to 96 cells/mm3 for an untreated individual. In a HAART-experienced individual HIV RNA was reduced by 0.34 log10 and 0.86 log10 at 1 and 2 years. The OZ1 effect was maximal when both CD4+ T lymphocytes and monocytes/macrophages were protected from successful, productive infection by OZ1. Conclusions The modelling indicates a single infusion of HSC cell-delivered gene therapy can impact on HIV viral load and CD4 T-lymphocyte count. Given that gene therapy avoids the complications associated with HAART, there is significant potential for this approach in the treatment of HIV. Copyright © 2009 John Wiley & Sons, Ltd. [source] Community reinforcement and family training: an effective option to engage treatment-resistant substance-abusing individuals in treatmentADDICTION, Issue 10 2010Hendrik G. Roozen ABSTRACT Aims Many individuals with substance use disorders are opposed to seeking formal treatment, often leading to disruptive relationships with concerned significant others (CSOs). This is disturbing, as untreated individuals are often associated with a variety of other addiction-related problems. Community Reinforcement and Family Training (CRAFT) provides an option to the more traditional treatment and intervention approaches. The objective of this systematic review was to compare CRAFT with the Alcoholics Anonymous/Narcotics Anonymous (Al-Anon/Nar-Anon) model and the Johnson Institute intervention in terms of its ability to engage patients in treatment and improve the functioning of CSOs. Methods The electronic databases PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Library were consulted. Four high-quality randomized controlled trials were identified, with a total sample of 264 CSOs. Data were synthesized to quantify the effect with 95% confidence intervals, using the random effects model. Results CRAFT produced three times more patient engagement than Al-Anon/Nar-Anon [relative risk (RR) 3.25, 95% confidence interval (CI) 2.11,5.02, P < 0.0001; numbers needed to treat (NNT) = 2] and twice the engagement of the Johnson Institute intervention (RR 2.15, 95% CI 1.28,3.62, P = 0.004; NNT = 3). Overall, CRAFT encouraged approximately two-thirds of treatment-resistant patients to attend treatment, typically for four to six CRAFT sessions. CSOs showed marked psychosocial and physical improvements whether they were assigned to CRAFT, Al-Anon/Nar-Anon or the Johnson Institute intervention within the 6-month treatment window. Conclusion CRAFT has been found to be superior in engaging treatment-resistant substance-abusing individuals compared with the traditional programmes. [source] Transthyretin as a potential CSF biomarker for Alzheimer's disease and dementia with Lewy bodies: effects of treatment with cholinesterase inhibitorsEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2010K. Schultz Background:, Previous studies have indicated that transthyretin (TTR) levels in cerebrospinal fluid (CSF) are altered in depression and dementia. The present study aimed to investigate whether CSF TTR can be used to discriminate between patients with Alzheimer's disease (AD) and patients with dementia with Lewy bodies (DLB) with or without medication, as well as to reveal whether CSF TTR correlates with depression in dementia. Methods:, CSF samples from 59 patients with AD, 13 patients with DLB and 13 healthy controls were collected, and biochemical analysis was performed. Subjects were assessed for the presence of depression. Results:, No significant differences in CSF TTR were found between AD, DLB, and control subjects or between depressed and non-depressed dementia patients. Interestingly, we found a significant reduction in CSF TTR (14%) in AD patients who were medicated with cholinesterase inhibitors compared to those AD patients who were not. Conclusions:, Significant reductions in CSF TTR were found after cholinesterase inhibitor treatment in patients with AD compared to untreated individuals. CSF TTR was unaltered in patients with DLB and had no relationship to depression in the present cohort with dementias. [source] Kinetics of lactate metabolism after submaximal ergometric exercise in HIV-infected patientsHIV MEDICINE, Issue 5 2004A-M Bauer Objectives It is unknown whether high levels of lactate result from enhanced production or decreased degradation. We therefore investigated differences in the kinetics of plasma lactic acid in HIV-infected patients receiving or not receiving highly active antiretroviral therapy (HAART) and in uninfected controls after submaximal ergometric exercise. Methods Ten healthy controls, 11 HIV-infected therapy-naïve patients, 15 HIV-infected patients on HAART with normal baseline lactate levels, and nine HIV-infected patients on HAART with elevated baseline lactate levels >2 mmol/L performed 10 min of ergometric exercise, with a heart rate of 200 beats/min minus age. Lactate levels were measured at baseline, at the end of exercise and 15, 30, 45, 60 and 120 min thereafter. Results Mean baseline lactate levels were 1.4, 1.5, 1.5 and 2.8 mmol/L in the controls, the therapy-naïve patients, the patients on HAART with normal lactate levels and the patients on HAART with elevated lactate levels, respectively. Maximum lactate levels after exercise were similar in all groups (9.7, 9.4, 9.0 and 10.1 mmol/L, respectively). Significant differences were found in the slope of lactate decline between controls and untreated individuals (P=0.038) and between patients on HAART with normal baseline lactate and patients on HAART with elevated baseline lactate (P=0.028). Conclusions Differences in lactate metabolism do exist between healthy controls and HIV-infected therapy-naïve individuals. Thus, HIV infection in itself may influence lactate levels. Elevated baseline lactate levels are associated with a delayed decline of lactate after exercise. These results could be explained by impaired lactate clearance. Lactate production upon exercise does not seem to be affected by baseline lactate levels. [source] Another look into the effect of premarital cohabitation on duration of marriage: an approach based on matchingJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 1 2009Stefano Mazzuco Summary., The paper proposes an alternative approach to studying the effect of premarital cohabitation on subsequent duration of marriage on the basis of a strong ignorability assumption. The approach is called propensity score matching and consists of computing survival functions conditional on a function of observed variables (the propensity score), thus eliminating any selection that is derived from these variables. In this way, it is possible to identify a time varying effect of cohabitation without making any assumption either regarding its shape or the functional form of covariate effects. The output of the matching method is the difference between the survival functions of treated and untreated individuals at each time point. Results show that the cohabitation effect on duration of marriage is indeed time varying, being close to zero for the first 2,3 years and rising considerably in the following years. [source] | ||||||||||