Validation and clinical use of the CECA, a disease-specific quality of life questionnaire for patients with anogenital Condylomata Acuminata

The aim of this validation study was to assess the measurement properties of the CECA (Spanish acronym for the Specific Questionnaire for Condylomata Acuminata) in patients with anogenital condylomas. A total of 247 patients aged > 18 years completed the questionnaire on 2 occasions as well as the Dermatology Life Quality Index (DLQI). The CECA questionnaire showed good internal consistency (Cronbach's alpha values of 0.86 and 0.91 in the emotional and sexual activity dimensions) and good testretest reliability (intraclass correlation coefficient 0.76 emotional dimension, 0.82 sexual activity dimension). Patients with de novo lesions and those with more extensive lesions and larger number of warts showed poorer health-related quality of life. CECA and DLQI scores correlated moderately. Patients whose lesions cleared at follow-up or with a reduction of >or= 50% showed a better improvement of health-related quality of life. The CECA questionnaire is a valid, reliable and sensitive tool for the assessment of health-related quality of life in patients with anogenital warts.

Combined low initial DNA damage and high radiation-induced apoptosis confers clinical resistance to long-term toxicity in breast cancer patients treated with high-dose radiotherapy

BACKGROUND. Either higher levels of initial DNA damage or lower levels of radiation-induced apoptosis in peripheral blood lymphocytes have been associated to increased risk for develop late radiation-induced toxicity. It has been recently published that these two predictive tests are inversely related. The aim of the present study was to investigate the combined role of both tests in relation to clinical radiation-induced toxicity in a set of breast cancer patients treated with high dose hyperfractionated radical radiotherapy. METHODS. Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma treated with high-dose hyperfractioned radical radiotherapy. Acute and late cutaneous and subcutaneous toxicity was evaluated using the Radiation Therapy Oncology Group morbidity scoring schema. The mean follow-up of survivors (n = 13) was 197.23 months. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radiation-induced apoptosis (RIA) at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. RESULTS. Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). Radiation-induced apoptosis increased with radiation dose (median 12.36, 17.79 and 24.83 for 1, 2, and 8 Gy respectively). We observed that those "expected resistant patients" (DSB values lower than 1.78 DSB/Gy per 200 Mbp and RIA values over 9.58, 14.40 or 24.83 for 1, 2 and 8 Gy respectively) were at low risk of suffer severe subcutaneous late toxicity (HR 0.223, 95%CI 0.073-0.678, P = 0.008; HR 0.206, 95%CI 0.063-0.677, P = 0.009; HR 0.239, 95%CI 0.062-0.929, P = 0.039, for RIA at 1, 2 and 8 Gy respectively) in multivariate analysis. CONCLUSIONS. A radiation-resistant profile is proposed, where those patients who presented lower levels of initial DNA damage and higher levels of radiation induced apoptosis were at low risk of suffer severe subcutaneous late toxicity after clinical treatment at high radiation doses in our series. However, due to the small sample size, other prospective studies with higher number of patients are needed to validate these results.

Different profiles of immune reconstitution in children and adults with HIV-infection after highly active antiretroviral therapy.

BACKGROUND Recent advances in characterizing the immune recovery of HIV-1-infected people have highlighted the importance of the thymus for peripheral T-cell diversity and function. The aim of this study was to investigate differences in immune reconstitution profiles after highly active antiretroviral therapy (HAART) between HIV-children and adults. METHODS HIV patients were grouped according to their previous clinical and immunological status: 9 HIV-Reconstituting-adults (HIV-Rec-adults) and 10 HIV-Reconstituting-children (HIV-Rec-children) on HAART with viral load (VL) or=500 cells/microL at least during 6 months before the study and CD4+ adults and 20 healthy-children (control subjects) were used to calculate Z-score values to unify value scales between children and adults to make them comparable. RESULTS HIV-Rec-children had higher T-cell receptor excision circles (TREC) and lower interleukin (IL)-7 levels than HIV-Rec-adults (p < 0.05). When we analyzed Z-score values, HIV-Rec-children had higher TREC Z-score levels (p = 0.03) than HIV-Rec-adults but similar IL-7 Z-score levels. Regarding T-cell subsets, HIV-Rec-children had higher naïve CD4+ (CD4+CD45RA hi+CD27+), naïve CD8+ (CD8+CD45RA hi+CD27+), and memory CD8+ (CD8+CD45RO+) cells/microl than HIV-Rec-adults, but similar memory CD4+ (CD4+CD45RO+) counts. HIV-Rec-children had lower naïve CD8+ Z-score values than HIV-Rec-adults (p = 0.05). CONCLUSION Our data suggest that HIV-Rec-children had better thymic function than HIV-Rec-adults and this fact affects the peripheral T-cell subsets. Thus, T-cell recovery after HAART in HIV-Rec-adults could be the consequence of antigen-independent peripheral T-cell expansion while in HIV-Rec-children thymic output could play a predominant role in immune reconstitution.

Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life.

CONTEXT The association between thyroid function during pregnancy and the later mental and psychomotor development of the child is supported by numerous experimental, clinical, and epidemiological studies. OBJECTIVE The aim of the study was to evaluate the psychological development of infants aged 3 to 18 months whose mothers had received 300 microg of potassium iodide during the first trimester of their pregnancy and compare with infants whose mothers had received no iodine supplements. DESIGN AND STUDY SUBJECTS: The study included 133 women who had received 300 microg of potassium iodine and 61 women who had received no iodine supplements. MAIN OUTCOME MEASURES The neuropsychological status of the children was evaluated with the Bayley Scales of Infant Development, and measurements were made of TSH, free T(3), free T(4), and urinary iodine. RESULTS Those children whose mothers had received an iodine supplement of 300 microg had a more favorable psychometric assessment than those of the other group of mothers. They had higher scores on the Psychomotor Development Index (P = 0.02) and the Behavior Rating Scale. CONCLUSIONS Dietary iodine supplements not only have no harmful effect on the neurodevelopment of the children, they may even be beneficial. Given the possible presence of confounding variables not controlled for in this study, these findings should be considered as preliminary.

Response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study.

BACKGROUND The purpose of this multicenter Spanish study was to evaluate the response to immediate-release methylphenidate by children and adults diagnosed with attention-deficit/hyperactivity disorder (ADHD), as well as to obtain information on current therapy patterns and safety characteristics. METHODS This multicenter, observational, retrospective, noninterventional study included 730 patients aged 4-65 years with a diagnosis of ADHD. Information was obtained based on a review of medical records for the years 2002-2006 in sequential order. RESULTS The ADHD predominantly inattentive subtype affected 29.7% of patients, ADHD predominantly hyperactive-impulsive was found in 5.2%, and the combined subtype in 65.1%. Overall, a significant lower Clinical Global Impression (CGI) score and mean number of DSM-IV TR (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision) symptoms by subtype were found after one year of treatment with immediate-release methylphenidate; CGI decreased from 4.51 to 1.69, symptoms of inattention from 7.90 to 4.34, symptoms of hyperactivity from 6.73 to 3.39, and combined subtype symptoms from 14.62 to 7.7. Satisfaction with immediate-release methylphenidate after one year was evaluated as "very satisfied" or "satisfied" by 86.90% of the sample; 25.75% of all patients reported at least one adverse effect. At the end of the study, 41.47% of all the patients treated with immediate-release methylphenidate were still receiving it, with a mean time of 3.80 years on therapy. CONCLUSION Good efficacy and safety results were found for immediate-release methylphenidate in patients with ADHD.

Use of the comet test to assess DNA damage in children with ataxia-telangiectasia and their relatives.

The electrophoresis of cells in alkaline medium (comet assay) is a valid technique for quantifying DNA damage in patients with ataxia-telangiectasia and their relatives.

Population pharmacokinetics of teicoplanin in children.

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens. A PK hospital-based study was conducted. Current dosage recommendations were used for children up to 16 years of age. Thirty-nine children were recruited. Serum samples were collected at the first dose interval (1, 3, 6, and 24 h) and at steady state. A standard 2-compartment PK model was developed, followed by structural models that incorporated weight. Weight was allowed to affect clearance (CL) using linear and allometric scaling terms. The linear model best accounted for the observed data and was subsequently chosen for Monte Carlo simulations. The PK parameter medians/means (standard deviation [SD]) were as follows: CL, [0.019/0.023 (0.01)] × weight liters/h/kg of body weight; volume, 2.282/4.138 liters (4.14 liters); first-order rate constant from the central to peripheral compartment (Kcp), 0.474/3.876 h(-1) (8.16 h(-1)); and first-order rate constant from peripheral to central compartment (Kpc), 0.292/3.994 h(-1) (8.93 h(-1)). The percentage of patients with a minimum concentration of drug in serum (Cmin) of <10 mg/liter was 53.85%. The median/mean (SD) total population area under the concentration-time curve (AUC) was 619/527.05 mg · h/liter (166.03 mg · h/liter). Based on Monte Carlo simulations, only 30.04% (median AUC, 507.04 mg · h/liter), 44.88% (494.1 mg · h/liter), and 60.54% (452.03 mg · h/liter) of patients weighing 50, 25, and 10 kg, respectively, attained trough concentrations of >10 mg/liter by day 4 of treatment. The teicoplanin population PK is highly variable in children, with a wider AUC distribution spread than for adults. Therapeutic drug monitoring should be a routine requirement to minimize suboptimal concentrations. (This trial has been registered in the European Clinical Trials Database Registry [EudraCT] under registration number 2012-005738-12.).