Estimating children's exposure to toxic elements in contaminated toys and children's jewelry via saliva mobilization.

Children's potential for exposure to potentially toxic elements in contaminated jewelry and toys via mouth contact has not yet been fully evaluated. Various toys and jewelry (metallic toys and jewelry [MJ], plastic toys, toys with paint or coating, and brittle/pliable toys; n = 32) were tested using the saliva extraction (mouthing) compartment of the DIN and RIVM bioaccessibility protocols to assess As, Ba, Cd, Cr, Cu, Mn, Ni, Pb, Sb, and Se mobilization via saliva. Total concentrations of As, Cd, Cu, Ni, Pb, and Sb were found elevated in analyzed samples. Four metals were mobilized to saliva from 16 MJ in significant quantities (>1 µg for highly toxic Cd and Pb, >10 µg for Cu and Ni). Bioaccessible concentrations and hazard index values for Cd exceeded limit values, for young children between 6 mo- and 3 yr-old and according to both protocols. Total and bioaccessible metal concentrations were different and not always correlated, encouraging the use of bioaccessibility for more accurate hazard assessments. Bioaccessibility increased with increasing extraction time. Overall, the risk from exposure to toxic elements via mouthing was high only for Cd and for MJ. Further research on children's exposure to toxic elements following ingestion of toy or jewelry material is recommended.

Safety and efficacy of once-daily nevirapine dosing: a multicohort study.

BACKGROUND: Nevirapine (NVP) is often prescribed once daily in clinical practice in combination with a once daily nucleoside backbone. We investigated the relationship of NVP dosing with safety and efficacy. METHODS: Patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort study, Canadian HAART Observational Medical Evaluation and Research (HOMER) cohort and Swiss HIV Cohort Study (SHCS) using NVP-based combination therapy either once daily or twice daily were included. Risk factors for discontinuing NVP because of hypersensitivity reactions (HSRs) were investigated using multivariate logistic regression. Risk factors for virological failure 96 weeks after NVP initiation were identified using logistic regression and Cox models. RESULTS: Of 5,636 patients (774 once daily and 4,862 twice daily), 268 (4.8%) discontinued NVP because of HSR between 2 and 18 weeks. Logistic regression showed that, compared with patients with detectable HIV type-1 (HIV-1) RNA starting twice-daily NVP, there was a significantly higher risk of discontinuation of once-daily NVP because of HSR in patients with detectable HIV-1 RNA at the start of NVP (odds ratio [OR] 1.52; P=0.04), whereas the risk was actually significantly lower in patients starting once-daily NVP with undetectable HIV-1 RNA (OR 0.44; P=0.04). Cox models showed that risk of virological failure was not different for twice- versus once-daily NVP in treatment-naive patients (twice-daily versus once-daily hazard ratio [HR] 1.01; P=0.95), treatment-experienced patients experiencing treatment failure (twice-daily versus once-daily HR 1.22; P=0.30) or patients with undetectable HIV-1 RNA simplifying treatment with NVP (twice-daily versus once-daily HR 1.29; P=0.30). CONCLUSIONS: Initiation of a once-daily NVP-based regimen in patients with suppressed viraemia carries a low risk of treatment-limiting HSR. Once- or twice-daily NVP-based regimens appear to have similar antiretroviral efficacy.

Excimer laser for psoriasis: a review of theories regarding enhanced efficacy over traditional UVB phototherapy.

BACKGROUND: Fiber-optically targeted ultraviolet B (UVB) therapy has been shown to clear plaques of psoriasis in a significantly fewer number of treatments and reduce overall cumulative UVB dose than traditional UVB phototherapy. OBJECTIVE: This article reviews existing theories in the literature attempting to explain the superior efficacy of targeted UVB. METHODS: Medline was used to perform a comprehensive review of the literature from 1965 to present. Only information from the English language journals are reported in this study. RESULTS: The theories proposed to explain the higher efficacy of the excimer (XeCl) laser relative to traditional UVB include the ability to use higher intensities of ultraviolet (UV) light and a more efficient induction of T cell apoptosis. CONCLUSION: The possible explanations for the superior efficacy of the excimer laser over traditional UVB therapy for psoriasis include: 1) a higher intensity UV light to plaques, which is more effective in clearing psoriasis; 2) penetration into the dermis where it may induce T cell apoptosis, potentially to a greater extent than the wavelength or given energy level predicts; and 3) the difference in the delivery of UVB light may result in cell death and skin immune system suppression more effectively than traditional UVB.

A randomized cross-over study to compare raltegravir and efavirenz (SWITCH-ER study).

BACKGROUND: Efavirenz (EFV) causes neuropsychiatric side-effects and an unfavorable blood lipid profile. We investigated the effect of replacing EFV with raltegravir (RAL) on patient preference, daytime sleepiness, sleep quality, anxiety, and lipid levels. METHOD: Switch-ER was a randomized, double-blind, cross-over study. Patients who tolerated EFV, with less than 50 copies/ml HIV-RNA, were randomized into two groups: the RAL-first group started with RAL (400 mg twice daily) and EFV placebo, and the EFV-first group with EFV (600 mg once daily) and RAL placebo. After 2 weeks, both groups switched to the alternate regimen. The primary endpoint was patient preference for the first or the second regimen, assessed after 4 weeks. RESULTS: Fifty seven participants were enrolled with a median CD4 cell count 600/µl, and duration of previous EFV therapy 3.4 years. Fifty three participants completed the study. When asked about treatment preference after 4 weeks, 22 preferred RAL and 12 preferred EFV, whereas 19 did not express a preference. A significant difference in anxiety and stress scores favoring RAL (P = 0.04 and 0.03, respectively) was observed. Median plasma cholesterol levels decreased by 0.4 mmol/l (16 mg/dl, P < 0.001), triglycerides by 0.2 mmol/l (18 mg/dl, P = 0.036), and low-density lipoprotein by 0.2 mmol/l (8 mg/dl, P = 0.004) after replacing EFV with RAL. After study completion, 51% of patients switched to RAL. CONCLUSION: Half of patients previously on a stable EFV preferred to switch to RAL, after double-blind exposure to RAL for 2 weeks. Substitution of EFV by RAL significantly impacted on lipid levels, stress, and anxiety scores.

A randomized crossover study to compare efavirenz and etravirine treatment.

BACKGROUND: Efavirenz (EFV) causes neuropsychiatric side-effects and an unfavourable blood lipid profile. We investigated the effect of replacing EFV with etravirine (ETR) on patient preference, sleep, anxiety and lipid levels. METHOD: Study participants did not complain of side-effects, had tolerated EFV for at least 3 months, with less than 50 copies/ml HIV-RNA. After randomization, the ETR-first group started with ETR (400 mg daily) [DOSAGE ERROR CORRECTED] with EFV-placebo and the EFV-first group with EFV with ETR-placebo. After 6 weeks, both groups switched to the alternate regimen. Nucleoside reverse transcriptase inhibitors were continued without any change. The primary end point was patient preference for the first or the second regimen, assessed after 12 weeks. RESULTS: Fifty-eight patients were enrolled with a median CD4 cell count of 589 cells/µl and the duration of previous EFV therapy was 3.9 years. Fifty-five patients completed the study. When asked about treatment preference after 12 weeks, 16 preferred EFV and 22 preferred ETR, whereas 17 did not express a preference (P = NS). Patients who continued EFV during the first phase of the trial preferred EFV (15/21, 71%), whereas patients who started with ETR were more likely to prefer ETR (n = 16/17, 94%). This order effect was strongly significant (P < 0.0001). Quality of sleep, depression, anxiety and stress scores did not differ significantly between groups. Median plasma cholesterol levels decreased by 0.7 mmol (29 mg/100 ml) after replacing EFV with ETR (P < 0.002). CONCLUSION: After substitution of EFV by ETR, patients did not express a significant preference for ETR. There was no measurable effect on neuropsychiatric symptoms and sleep. Cholesterol decreased.

HIV increases markers of cardiovascular risk: results from a randomized, treatment interruption trial.

OBJECTIVES: Plasma soluble inflammatory molecules are associated with the risk of ischaemic cardiovascular events. We investigated whether HIV replication modified the levels of these proteins in a combination antiretroviral therapy (cART) interruption trial. METHOD AND RESULTS: In 145 HIV-infected Thai patients (62% women, median CD4 cell count 271 cells/microl, median plasma HIV-RNA 4.66 log10 copies/ml) included in the Swiss-Thai-Australia Treatment Interruption Trial (STACCATO) trial, leptin, adiponectin, C-reactive protein, soluble vascular cell adhesion molecule-1 (s-VCAM-1), P-selectin, chemokine ligand 2, chemokine ligand 3, interleukin (IL)-6, IL-10, granulocyte macrophage colony-stimulating factor and D-dimer were measured before cART was initiated, after cART had suppressed HIV replication to less than 50 copies/ml plasma (median 8 months) and again 12 weeks after randomization to continued cART (n=48) or interrupted cART (n=97). Multiple linear regression and logistic regression were used to investigate the association between each cardiovascular marker and plasma HIV-RNA. Initiation of cART resulted in significant declines in s-VCAM-1, P-selectin, leptin and D-dimer, whereas mediators with anti-inflammatory properties, such as adiponectin and IL-10, increased. At 12 weeks after randomization, we found positive associations between levels of s-VCAM-1 and chemokine ligand 2 with an increase in plasma HIV-RNA (r=0.271, P=0.001 and r=0.24, P=0.005, respectively), whereas levels of adiponectin decreased for each 1 log increase in plasma HIVRNA (r=-0.24, P=0.002). Detectable IL-10 was less likely (odds ratio = 0.64, 95% confidence interval = 0.43-0.96) for each 1 log increase in plasma HIV-RNA. CONCLUSION: Plasma levels of several inflammatory, anti-inflammatory and endothelial activation markers of cardiovascular disease are associated with HIV-RNA replication.

An attempt to formulate an evidence-based strategy in the management of moderate-to-severe psoriasis: a review of the efficacy and safety of biologics and prebiologic options.

Psoriasis is a chronic skin disorder affecting up to 2.5% of the world's population. Despite the myriad treatment options available, there is no uniformly accepted therapeutic approach for moderate-to-severe psoriasis. The objective of this review is to evaluate the relative efficacy and safety of available therapeutic options and to formulate general recommendations for the treatment of moderate-to-severe psoriasis. MEDLINE and Evidence Based Medicine (Cochrane) were used to perform a comprehensive search of the literature from 1986 to 2006. The most scientifically rigorous clinical trial published in the literature was selected for Psoriasis Area and Severity Index (PASI 75) comparison. Only information from clinical trials, human subjects and English language journals are reported in this study. The percentage of PASI 75 reduction at approximately 12 weeks obtained by the following treatment options were: Goeckerman and RePUVA, 100%; calcipotriene plus PUVA, 87%; ciclosporin, 78.2-80.3%; infliximab, 80%; adalimumab 40 mg every other week, 53% and 40 mg/week, 80%; PUVA, 63%; methotrexate, 60%; NB-UVB, 55%; acitretin 52%; etanercept 50 mg twice weekly, 49% and 25 mg twice weekly, 34%; efalizumab, 31.4%; and alefacept 21%. Psoriatic treatments with safer profiles compared with other agents include bath PUVA, Goeckerman and RePUVA. Based on the literature review of efficacy and safety of biologics and prebiologic treatment options for moderate-to-severe psoriasis, the risk:benefit ratio seems most favorable for Goeckerman and RePUVA, followed by either etanercept or adalimumab.