Predictors of neurocognitive performance in chronic pain patients

In a sample of 70 chronic pain patients, hierarchical multiple regression analyses were utilized to assess the additive and interactive contributions of pain severity and psychological distress variables to neurocognitive performance across attention and concentration, memory, and reasoning ability domains. Although the full model predicting attention and concentration was found to be significant, there was no significant contribution of pain severity, psychological distress, or the Pain Severity x Psychological Distress interaction to the prediction of attention and concentration scores after controlling for the effect of years of formal education. After controlling for the effect of years of formal education, pain severity and psychological distress did make separate and significant contributions to the prediction of memory scores; however, the Pain Severity x Psychological Distress interaction did not significantly affect memory scores. After controlling for the effect of years of formal education, there was no significant contribution of pain severity, psychological distress, or the Pain Severity x Psychological Distress interaction to reasoning ability scores. Results suggest the importance of assessing memory function when managing psychologically distressed chronic pain patients.     

Polyneuropathies in patients treated with HAART in Bobo-Dioulasso hospital, Burkina Faso

Peripheral neuropathies (PN) represent the most common neurological manifestation in patients with HIV infection. Introduction of highly active antiretroviral therapy (HAART) had a significant impact on the epidemiology of HIV-associated neuropathies even in poor-resources countries. HIV-infected patients were followed up over a 2-years period from January 2002 to December 2003. PN was clinically diagnosed based on abnormalities of ankle reflexes or vibratory perception and if patients described pain, paresthesia or numbness. Electromyography was not performed in this study Among the 133 HIV-infected patients treated with HAART 31 patients (23 females and 8 males) with 38.8 of mean age were followed up for PN. 95.5% among them were HIV1-infected. According to the availability of the antiretroviral therapy, 9 patients were treated with protocol A including lamivudine + stavudine + nevirapine, 12 patients with protocol B including combination of stavudine + lamivudine + efavirenz, and 10 patients with protocol C with other combinations of antiretroviral therapies. Average CD4 cell count was 229.3/microl and 60% of the sample had < 200 CD4 cell counts at the time of diagnosis. PN occurred within 5.6 months from the institution of the HAART and 80% less than 3 months after the beginning of the treatment. Burning feet syndrome was found in 16.1% of the sample. 45.2% of polyneuropathies occurred in late stage of HIV infection (< 200 CD4/microl). The presence of PN was related to decreased CD4 cells counts and neurotoxic antiretroviral therapy Introduction of HAART has modified the course and the prognosis of HIV infection even in poor resources setting. The incidence of toxic neuropathies is increasing with longer patients' life expectancy and represents a major factor in treatment limitation and the neurological side effects of HAART should be well identified by physicians.     

Progression of HIV-associated dementia treated with HAART

A consecutive series of 96 patients with HIV-associated dementia treated with HAART were studied to identify specific clinical factors associated with an improved response to therapy. The Memorial Sloan-Kettering dementia severity scale and the HIV Dementia Scale were used to assess outcomes. Of 30 patients meeting the inclusion criteria with adequate follow-up, 60% improved neurologically and 40% progressed. There was a trend toward improvement associated with plasma viral suppression, whereas progression was strongly associated with injection drug use history (odds ratio, 13.3). Age, ethnicity, gender, adherence, and predicted CNS penetrance of HAART were not associated with improved outcomes.     

妊娠期调节性T细胞介导保护性效应需要同种抗原的刺激

越来越多的证据表明,人和小鼠妊娠期CD4+CD25+调节性T细胞(Treg)参与介导母胎免疫耐受。然而,目前对于妊娠期间调控Treg变化的因素还不清楚,对同基因交配(BALB/c×BALB/c)和异基因交配(BALB/c×C57)小鼠以及妊娠妇女CD4+CD25+Treg进行了分析,以探讨雌、孕激素和胎儿同种异基因抗原对Treg的影响。发现异基因孕鼠外周淋巴器官CD4+CD25+T细胞于早孕、中孕期明显高于非孕对照,而在同基因孕鼠只有少数个例升高;这些CD4+CD25+T细胞均表达Foxp3蛋白,在体外具有无反应性和免疫抑制能力;而且异基因孕鼠淋巴细胞对父方同种抗原的应答强度明显弱于同基因孕鼠。对去势的雌鼠给予雌二醇或孕酮,使其在血清中浓度接近中孕水平,未发现外周血CD4+CD25+Treg的明显变化。妊娠妇女CD4+CD25highTreg在早孕、中孕期显著升高,临近分娩期降至非孕水平,而此时CD4+CD25lowT细胞反而增加。以上结果表明,异基因抗原的存在对于妊娠期CD4+CD25+Treg介导对胎儿的免疫保护效应具有重要作用,而CD4+CD25+Treg的消失可能与分娩的发动有一定关系。     

Changes in the HIV-1 mutational profile before first-line HAART in the RESINA cohort

Sporadic observations have shown changing patterns of transmitted drug resistance mutations (TDRMs) in HIV infection even without selection pressure by antiretroviral treatment (ART). Repeated genotypic resistance analyses in treatment‐naïve patients were performed, in order to analyze intraindividual variances of resistance patterns over time. Between the years 2001 and 2008 two genotypic resistance tests were performed at different time‐points in 49 treatment‐naïve HIV‐positive patients aged >18 years. Wild‐type virus was found at baseline and during follow‐up in 31 patients (group A, median time between resistance tests 146 days), while resistance mutations were found either at baseline or during follow‐up in 18 patients (group B, median time between resistance tests 297 days). In group B, the pattern of resistance changed in eight out of 18 patients over time, with three patients showing decreasing numbers and five patients showing increasing numbers of resistance mutations. The pattern of resistance mutations remained unchanged in 10 out of 18 patients. The mutational pattern in untreated HIV infection may change over time and a single resistance analysis may underestimate the true prevalence of preserved resistance mutations. If these findings can be confirmed in a larger number of patients, it would be prudent to perform genotypic resistance testing both at baseline and prior to the start of ART in order to capture a more complete picture of preserved mutations before initiating ART. J. Med. Virol. 83:187–195, 2011. © 2010 Wiley‐Liss, Inc.     

Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART

BACKGROUND: Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse. METHODS: This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels > or =200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model. RESULTS: One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71). CONCLUSIONS: There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.     

Significant link between sCD30 changes and HIV viremia in patients treated with HAART

Elevated sCD30 levels were generally associated with poor prognosis in chronic HIV infection prior to the era of highly active antiretroviral therapy (HAART). Little information is available on sCD30 and HIV-1 viremia. In this study, the association between sCD30 and HIV-1 viremia was investigated in HIV-infected patients who underwent HAART. sCD30 was measured in 276 patients prior (T0) and 6 months after HAART (T6). Standard survival analyses were used to evaluate the prognostic value of sCD30 and sCD30 change from baseline to predict the virological response to HAART. Higher levels (>30 U/ml) of sCD30 prior to HAART were associated with relatively higher viremia (P = 0.0001) and tended to be associated with a lower chance of achieving virological success (P = 0.13). The median T6 sCD30 level in patients who concomitantly had viremia >500 copies/ml was higher than the median sCD30 level of those with viremia 相似文献   

Antiretroviral treatment simplification with 3 NRTIs or 2 NRTIs plus nevirapine in HIV-1-infected patients treated with successful first-line HAART

OBJECTIVES: To assess the virologic noninferiority of an antiretroviral treatment simplification with coformulated zidovudine/lamivudine/abacavir (group 1) vs. coformulated zidovudine/lamivudine plus nevirapine (group 2) in HIV-1-infected patients receiving successful first-line highly active antiretroviral therapy. METHODS: This is a prospective, multicenter, open-label, comparative, randomized, noninferiority study. A delta of 15% for differences in virologic suppression <200 copies/mL between groups was prespecified with a 1-sided 0.025 significance level. RESULTS: A total of 134 patients were included into this study: 68 were allocated to group 1 and 66 to group 2. By intention-to-treat analysis (switch equals failure), the percentage of virologic suppression <200 copies/mL (<50 copies/mL) at week 48 was 71.0% (65.1%) and 73.0% (63.3%) in groups 1 and 2, respectively (estimate for differences [<200 copies/mL]: -2.1, 95% CI: -17.4-13.1, P=0.783). Thirteen and 14 patients in groups 1 and 2, respectively, discontinued therapy due to adverse events. Dyslipidemia improved in both groups, with a higher improvement in low-density lipoprotein cholesterol (P=0.049) in group 1. CONCLUSIONS: Group 1 is not inferior to group 2 regarding virologic suppression <200 copies/mL. Both strategies improve lipid profile.     

Core neurocognitive functions in children treated for posterior fossa tumors

Identifying cognitive deficits associated with pediatric brain tumors and their treatment is important in delineating the mechanisms of intellectual decline often associated with these diseases. The authors evaluated sustained attention, information processing speed, working memory, and IQ in 64 patients with posterior fossa tumors, including those treated with either: (a) surgery and cranial radiation (n = 32), and (b) surgery without radiation (n = 32). Ten patients treated for non-CNS solid tumors were included as a comparison group. The authors also examined the impact of relevant demographic and medical variables on neurocognitive outcome. The authors found that neither age at, nor time since, diagnosis predicted cognitive outcome in this sample. Further, sustained attention and working memory were largely intact and there were no differences between groups. Patients treated with cranial radiation demonstrated lowered short-form IQ and slow information processing speed: Patients treated with cranial radiation and who experienced postsurgical complications demonstrated the poorest performance. The authors consider information processing speed to be an excellent candidate mechanism in understanding the impact of cranial radiation on intellectual outcome.     

Cognitive performance in multiple trauma patients 3 years after injury.

OBJECTIVES: Patients with sequelae from multiple trauma commonly display cognitive disturbances, specifically in the areas of attention and memory. This study was designed to assess cognitive functioning 3 years after severe multiple trauma and to investigate how cognitive performance is related to head injury severity and psychological distress respectively. METHODS: Sixty-eight multiple trauma patients were tested with a screening battery consisting of six neuropsychological tasks 3 years after injury. A measure of psychological distress (20-item General Health Questionnaire, or GHQ-20) was also administered. RESULTS: Patients who neither showed signs of reduced consciousness on admission to the hospital nor reported significant psychological distress at follow-up tended to have normal test performance. In five of the six tasks, cognitive impairment was related to the severity of the traumatic brain injury as measured by the Glasgow Coma Scale (GCS). In both attention span tasks, patients designated as cases by the GHQ had significantly lower scores than noncase patients. These bivariate relationships were upheld in multiple regression analyses, in which age, sex, and GCS and GHQ scores were entered as independent variables. When patients with severe head injuries were excluded from the analyses, GCS scores still contributed to the variance in tests of verbal attention span and delayed recall, but performance on attentional tasks was more strongly related to psychological distress than to GCS scores. CONCLUSIONS: Cognitive deficits in multiple trauma patients were related both to the severity of the traumatic brain injury and to the degree of psychological distress. The strength of the association between brain injury as indicated by GCS scores and cognitive performance differed between different tasks. Neuropsychological testing may assist in differentiating primary organic from secondary psychogenic impairments.     

Changes in knee motion over the first 3 years with a mobile-bearing prosthesis

The present work aims to evaluate the mobility of the polyethylene bearing in 25 patients implanted with a mobile-bearing PCL-retaining TKR (Interax ISA, Striker Howmedica) under in vivo, weight-bearing conditions over 3 years' follow-up. We compared the bearing motion in response to specific tests in two consecutive follow-ups with Roentgen Stereophotogrammetric Analysis (RSA). Results showed that polyethylene continued to displace on the tibial baseplate over time: longitudinal rotations and medio-lateral translations tended to increase at the second follow-up (mean increases 0.7+/-2.5 degrees and 0.34+/-1.08 mm, respectively), while sagittal translations did not show any relevant change. Longitudinal rotations and AP translations were preserved when present at both follow-ups. Nevertheless, no statistical evidence of repeatable pattern of motion was found, since bearings frequently reversed their pattern of motion between the two follow-ups. The unconstrained polyethylene mobility resulted in an unrepeatable, erratic pattern of bearing motion intra-patient and over time. The changes in knee motion were found not to affect the clinical results over the first 3 years of follow-up. As in a fixed-bearing design, mobile-bearing design was not able to reproduce normal knee kinematics.     

Changes in thymus volume in adult HIV-infected patients under HAART: correlation with the T-cell repopulation

An important thymus role has been suggested in T‐cell repopulation after HAART in adult HIV‐1 infected patients. Thymus volume increase after treatment has been described in HIV‐1 infected children but not in adult patients. The objective of this work was to evaluate the effect of HAART on the thymic volume of adult HIV‐1 infected patients and its relation with the T‐cell repopulation. Twenty‐one adult patients following 24 weeks under HAART were included in the study. All patients underwent a thoracic computed tomography (CT) evaluation for the measurement of thymic volumes at weeks 0, 12 and 24. Baseline thymus volume showed a significant correlation with the patient's age. Thymic volume significantly increased after 24 weeks of HAART. Besides, a significant correlation between changes in the thymus volume and changes in both total and naïve CD4+ cell counts was found. Only patients with increases ≥100 CD4+ cell counts after treatment significantly increased the thymic volume. These data show the first evidence of an early change in thymic volume of adult HIV‐1 infected patients under HAART. This increase was related to the rise of both total and naïve CD4+ cell counts suggesting a functional role of thymic volume increase.     

Viral load assay sensitivity and low level viremia in HAART treated HIV patients

BackgroundThe recent introduction of highly sensitive viral load assays resulted in a significant increase in number of treated HIV-infected patients with a detectable viral load. The significance of a viral load between 20 and 50 copies/mL remains unclear.ObjectivesTo compare the performance of three viral load assays, with special attention for specificity and sensitivity at the lowest level of quantification.Study designSamples (n = 181) were selected from 62 HIV-positive individuals that experience viral blips or episodes of low but detectable viremia under antiretroviral treatment, and from 216 HIV-negative individuals. Each sample was tested in at least two of three assays: the Cobas Amplicor HIV-1 Monitor (CAP/CA), the Cobas Ampliprep/Cobas TaqMan HIV-1 version 1 (CAP/CTM1) and the Cobas Ampliprep/Cobas TaqMan HIV-1 version 2 (CAP/CTM2).ResultsNo false positive results were recorded. Kappa statistics revealed fair to moderate agreement between the results of the three assays, but important differences in sensitivity were observed, with the highest sensitivity reported for CAP/CTM2 followed by CAP/CTM1 and CAP/CA. The differences in sensitivity remained after equalization of the detection limit for all assays at 50 copies/mL. Analysis of samples collected over time showed that patients with single blips in CAP/CA present with recurrent blips in CAP/CTM1 and persistent detectable viremia in CAP/CTM2.ConclusionsViral load results between 20 and 50 copies/mL in either CAP/CTM1 or CAP/CTM2, indicate true viremia. The availability of highly sensitive assays force reconsideration of the terms ‘undetectable’ viral load and ‘virological success’ of antiretroviral treatment.     

Epstein-Barr virus and human immunodeficiency virus serological responses and viral burdens in HIV-infected patients treated with HAART

Epstein-Barr virus (EBV) associated non-Hodgkin lymphoma is recognized as a complication of human immunodeficiency virus (HIV) infection. Little is known regarding the influence of highly active antiretroviral therapy (HAART) on the biology of EBV in this population. To characterize the EBV- and HIV-specific serological responses together with EBV DNA levels in a cohort of HIV-infected adults treated with HAART, a study was conducted to compare EBV and HIV serologies and EBV DNA copy number (DNAemia) over a 12-month period after the commencement of HAART. All patients were seropositive for EBV at baseline. Approximately 50% of patients had detectable EBV DNA at baseline, and 27/30 had detectable EBV DNA at some point over the follow-up period of 1 year. Changes in EBV DNA copy number over time for any individual were unpredictable. Significant increases in the levels of Epstein-Barr nuclear antigen (EBNA) and Epstein-Barr early antigen (EA) antibodies were demonstrated in the 17 patients who had a good response to HAART. Of 29 patients with paired samples tested, four-fold or greater increases in titers were detected for EA in 12/29 (41%), for EBNA in 7/29 (24%), for VCA-IgG in 4/29 (14%); four-fold decreases in titers were detected in 2/29 (7%) for EA and 12/29 (41%) for EBNA. A significant decline in the titer of anti-HIV antibodies was also demonstrated. It was concluded that patients with advanced HIV infection who respond to HAART have an increase in their EBV specific antibodies and a decrease in their HIV-specific antibodies. For the cohort overall, there was a transient increase in EBV DNA levels that had declined by 12 months.     

Changes in fine motor retardation in depressed patients treated with fluoxetine

Changes in psychomotor slowing were studied in 21 inpatients with a Major Depressive Episode. Fine motor retardation was measured and analysed using computer-aided drawing and figure-copying tasks at T0 (the start of 6 weeks treatment with fluoxetine 20 mg/day) and 5 weeks later (T1). The differences in reaction time between the patients and a group of healthy, matched controls at T0 had disappeared at T1. The initial motor deficit, expressed in longer movement times, had not improved at T1. These findings combined with the effect of manipulation of cognitive and motor demands, suggested that only cognitive processes had accelerated.