Patients undergoing recurrent CT exams: assessment of patients with non-malignant diseases,reasons for imaging and imaging appropriateness

To determine percent of patients without malignancy and ≤ 40 years of age with high cumulative radiation doses through recurrent CT exams and assess imaging appropriateness. From the cohort of patients who received cumulative effective dose (CED) of ≥ 100 mSv over a 5-year period, a sub-set was identified with non-malignant disease. The top 50 clinical indications leading to multiple CTs were determined. Clinical decision support (CDS) system scores were analyzed using a widely adopted standard of 1–3 (red) as “not usually appropriate,” 4–6 (yellow) “may or may not be appropriate,” and 7–9 (green) “usually appropriate.” Clinicians reviewed patient records to assess compliance with appropriate use criteria (AUC). 9.6% of patients in our series were with non-malignant conditions and 1.4% with age ≤ 40 years. CDS scores (rounded) were 2% red, 38% yellow, 27% green, and 33% unscored CTs. Clinical society guidelines for CT exams, wherever available, were followed in 87.5 to 100% of cases. AUCs were not available for several clinical indications as also referral guidelines for serial CT imaging. More than half of CT exams were unrelated to follow-up of a primary chronic disease. We are faced with a situation wherein patients in age ≤ 40 years require or are thought to require many CT exams over the course of a few years but the radiation risk creates concern. There is a fair number of conditions for which AUC are not available. Suggested solutions include development of CT scanners with lesser radiation dose and further development of appropriateness criteria.     

Population pharmacokinetics of tanezumab in phase 3 clinical trials for osteoarthritis pain

AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V ₁), peripheral volume (V ₂), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day^–1, 2.71 l, 1.98 l, 0.371 l day^–1, 8.03 μg day^–1 and 27.7 ng ml^–1, respectively. Inter‐individual variability (IIV) was included on CL, V ₁, V ₂ and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V ₁ and V ₂ significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit.     

Aggressive behavior linked to corticotropin-reactive autoantibodies.

BACKGROUND: Altered stress response is characteristic for subjects with abnormal aggressive and antisocial behavior, but the underlying biological mechanisms are unclear. We hypothesized that autoantibodies (autoAbs) directed against several stress-related neurohormones may exist in aggressive subjects. METHODS: Using enzyme-linked immunosorbent assay, we studied whether autoAbs directed against corticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), oxytocin, and vasopressin are present in serum of male subjects with conduct disorder and prisoners with history of violence. Healthy blood donors served as control subjects. RESULTS: Both conduct disorder and prisoners groups displayed strongly increased levels of ACTH-reactive immunoglobulin G (IgG) and immunoglobulin M (IgM) autoAbs compared with control subjects. Levels of oxytocin-reactive IgM autoAbs were slightly increased in both groups of aggressive subjects, whereas levels of vasopressin-reactive IgG and IgM autoAbs were lower only in conduct disorder. No differences in the levels of alpha-MSH-reactive autoAbs were found between aggressive and control subjects. CONCLUSIONS: High levels of ACTH-reactive autoAbs as well as altered levels of oxytocin- and vasopressin-reactive autoAbs found in aggressive subjects may interfere with the neuroendocrine mechanisms of stress and motivated behavior. Our data suggest a new biological mechanism of human aggressive behavior that involves autoAbs directed against several stress-related neurohormones.     

Secondary correction of the unilateral cleft nose deformity with an endonasal technique

Summary Malposition of the nasal bone, septum and the alar cartilage are striking features of the unilateral cleft nose deformity. An endonasal technique (the extramucosal) was used in 26 patients, aged 13–38 (median 19), to correct aesthetic and functional problems. Twenty-four patients were secondary and two were tertiary. The patients were followed from 1–9 years. The pathological anatomy of the septum varied considerably, so different types of septoplasties had to be done. In 20 patients, satisfactory aesthetic and functional results were obtained in one operation. Secondary corrections were indicated in six patients. In cases with no gross scarring in or around the alar cartilage, the form and position of this cartilage will be more normal once the alar cartilages have been undermined and the deviation of the nasal bone and the septum is corrected.     

Attempt at predicting paraphrenic outcome in young, first admitted schizophrenic patients

A sample of 110 consecutive first admission young schizophrenic patients treated between 1964 and 1967 was rediagnosed in 1981. Among 92 survivors, 27 could be labelled as paraphrenics. From information available at inception 97 variables were coded covering such areas as personality, previous disturbances, age and type of onset, and symptoms around admission. Sixty-three out of 97 variables were hypothesized to differentiate, at admission, future paraphrenics from the rest of the sample. Paraphrenics were found to have had less contact disturbance, better self-esteem, less neurotic symptoms in adolescence and childhood, and less complaints of unhappiness when growing up. They had more regressive and paranoid symptoms at admission, were older at onset of the disease, which was more acute, more often connected with precipitating events, and confusion. Certain non-regressive symptoms such as brooding, anhedonia and concentration difficulties were less common. A discriminant analysis yielded a proportion of correct predictions = 0.64 (p less than 0.05). The results are in accordance with the theory of more favourable energetic and organizational capacity in paranoid schizophrenics as compared with non-paranoids.     

From altus to parvus: cardiac fatigue in athletes: reply

We would like to thank Professor Erdem Kasikcioglu for his interestin our article. In response to the initial question of why exhaustivephysical activity suppresses diastolic function,