Stability and Change of Psychopathology Symptoms Throughout Childhood and Adolescence

Child Psychiatry & Human Development - Assessing stability and change of children’s psychopathology symptoms can help elucidate whether specific behaviors are transient developmental...     

Evaluation of biomarkers for treatment selection using individual participant data from multiple clinical trials

Biomarkers that predict treatment effects may be used to guide treatment decisions, thus improving patient outcomes. A meta‐analysis of individual participant data (IPD) is potentially more powerful than a single‐study data analysis in evaluating markers for treatment selection. Our study was motivated by the IPD that were collected from 2 randomized controlled trials of hypertension and preeclampsia among pregnant women to evaluate the effect of labor induction over expectant management of the pregnancy in preventing progression to severe maternal disease. The existing literature on statistical methods for biomarker evaluation in IPD meta‐analysis have evaluated a marker's performance in terms of its ability to predict risk of disease outcome, which do not directly apply to the treatment selection problem. In this study, we propose a statistical framework for evaluating a marker for treatment selection given IPD from a small number of individual clinical trials. We derive marker‐based treatment rules by minimizing the average expected outcome across studies. The application of the proposed methods to the IPD from 2 studies in women with hypertension in pregnancy is presented.     

Comparative in vitro activities of aztreonam, ciprofloxacin, norfloxacin, ofloxacin, HR 810 (a new cephalosporin), RU28965 (a new macrolide), and other agents against enteropathogens.

The in vitro activity of drugs currently used in the treatment of diarrhea against 595 enteropathogens from worldwide sources was compared with that of six newly developed antibiotics, ciprofloxacin; norfloxacin; ofloxacin; aztreonam; HR810, an expanded-spectrum cephalosporin; and RU28965, a new macrolide. In contrast with ampicillin and chloramphenicol, trimethoprim-sulfamethoxazole showed an excellent activity against all of the enteropathogens tested, except Campylobacter species. Ciprofloxacin had the highest activity, with an overall 90% MIC of less than or equal to 0.097 micrograms/ml, except for Campylobacter species (0.39 micrograms/ml). Unlike other cephalosporins, HR810 showed a satisfactory activity against Campylobacter species (90% MIC of 3.12 micrograms/ml). RU28965 was three times less active than erythromycin against Campylobacter species.     

Synthesis and some properties of sulfate esters and sulfamates of iodothyronines

In the present study, convenient methods have been developed for the synthesis of sulfate derivatives of iodothyronines. Reaction with chlorosulfonic acid in dimethylformamide gave rise to formation of the sulfate ester with the phenolic hydroxyl group. Reaction with the sulfurtrioxide-trimethylamine complex in alkaline medium afforded the sulfamate with the alpha-amino group of the alanine side chain. The sulfated products were isolated by adsorption onto Sephadex LH-20 in acidic medium, followed by desorption with water. Iodide was not retarded on these columns, whereas elution of native iodothyronines required alkaline ethanol mixtures. The yield of both reactions varied between 70-90%. The sulfates and sulfamates of T4, T3, rT3, and 3,3'-diiodothyronine could be separated by reverse phase HPLC. The sulfamates exhibited high cross-reactivities with antibodies against free iodothyronines, in contrast to the low activities of the sulfates. Products were further characterized by proton nuclear magnetic resonance, TLC, and hydrolysis by acid or sulfatase activity. The availability of large quantities of pure iodothyronine sulfates and sulfamates should facilitate the study of the importance of sulfate conjugation in the metabolism of thyroid hormone.     

Clinical features and outcome in childhood T-cell leukemia-lymphoma according to stage of thymocyte differentiation: a Pediatric Oncology Group Study

The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment.     

Awareness of and attitudes towards infertility and its treatment： a cross-sectional survey of men in a United States primary care population

Previous studies have described racial and socioeconomic disparities in the treatment of infertility. Patient factors such as attitudes and awareness may be contributing factors. Since primary care is often the setting that serves as an entry into other areas of medicine, we sought to evaluate men＇s attitudes and awareness of male infertility in the primary care setting. To do this, we performed a cross-sectional survey of men＇s attitudes toward men＇s health issues in 210 men from two primary care clinic waiting rooms in Atlanta, Georgia. The survey was self-administered with closed-ended question items and was approximately 20 min in length. Of the 310 men approached, 210 agreed to participate and returned completed surveys. Overall, 52% of men said they were ＂very＂ or ＂somewhat＂ familiar with infertility and 25% were familiar with treatments for infertility. Some men had heard of surgery （21%） and medication （35%） as treatments for male infertility. Awareness and familiarity with the condition was greater in high socioeconomic status men （i.e. college graduates or those with income 〉$100 k per year） but did not differ by race on multivariate analysis. Attitudes toward infertility varied by race with non-Caucasian men being more likely to indicate that infertility is a serious condition, to be concerned about infertility, and to believe it decreases a man＇s quality-of-life. Therefore, a lack of awareness, but not negative attitudes, may contribute to previously-described disparities in the treatment of infertility.     

Increased Concentration of C-Reactive Protein in Obese Patients with Type 2 Diabetes Is Associated with Obesity and Presence of Diabetes but Not with Macrovascular and Microvascular Complications or Glycemic Control

The purpose of this study was to assess the concentration of C-reactive protein (CRP) in obese type 2 diabetes mellitus (DM2) patients and its association with macrovascular and microvascular complications. The study group consisted of 80 obese DM2 patients, including 20 macrovascular, 20 microvascular, 20 both macrovascular and microvascular, and 20 with no complications patients. The control group comprised 40 normoglycemic subjects—20 obese and 20 of normal body weight. Highly sensitive CRP and metabolic control parameters were assessed. CRP levels in obese diabetes subgroups and normoglycemic obese were similar and significantly higher than those in nonobese controls. No correlation was found between CRP and diabetes control parameters. There was a strong positive correlation between CRP level and body mass index in all groups. A multivariate analysis showed that DM2 and obesity are independent factors increasing CRP levels. Increased concentration of CRP in obese DM2 patients is related to obesity and diabetes itself. The lack of association between CRP and vascular complications remains unclear.