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.     

A drug safety evaluation of mogamulizumab for the treatment of cutaneous T-Cell lymphoma

Introduction: Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin lymphomas of skin-homing T-cells that initially or mainly manifest cutaneously. Treatment of CTCL is challenging given the disease states’ varying presentation and prognosis. Systemic treatment options often lack comparative evidence and have relatively low response rates and short duration of response. The recent Food and Drug Administration (FDA) approval of mogamulizumab in adult patients with relapsed or refractory (R/R) CTCL after at least one prior line of therapy provided a new treatment option to patients with advanced disease.

Areas covered: The authors discuss basic information about CTCL and mogamulizumab’s mechanism of action. Then, the authors discuss the agent’s efficacy. Finally, the authors evaluate the safety of mogamulizumab in comparison to other agents available in CTCL.

Expert opinion: Mogamulizumab has been shown to be an effective and well tolerated therapy for patients with relapsed and refractory MF/SS with excellent activity in the circulating component of the disease.     

Impact of ceftazidime restriction on gram-negative bacterial resistance in an intensive care unit

The present study included three periods: (1) a 12-month prerestriction and control period in 2001; (2) a 12-month restriction period with reduced ceftazidime prescribing in favor of piperacillin-tazobactam (2002); (3) and a 24 month postrestriction period (2003–2004). Note that, for results, P represents the difference between 2002 and 2001; P′, the difference between 2003 and 2001; and P″, the difference between 2004 and 2001. No changes in hygiene practices were observed during these three periods. The purpose of this study was to assess the effect of reducing ceftazidime use in an intensive care unit (ICU) upon Gram-negative bacterial resistance, particularly as regards Pseudomonas aeruginosa. During the three periods of the study, patients were similar concerning age, Simplified Acute Physiology Score (SAPSII), the site of nosocomial infection, and the requirements for mechanical ventilation (75% in 2001, 76% in 2002, 74% in 2003, and 85% in 2004). The most commonly isolated pathogens were P. aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. The use of ceftazidime decreased significantly from 12.6% in 2001 to 9% in 2002, to 3% in 2003 (P′ = 0.0009), and 2.6% in 2004 (P″ = 0.0001) in favor of piperacillin-tazobactam (0% 2001 to 3.7% in 2003; P′ = 0.002; and 5% in 2004; P″ = 0.0001). Simultaneously, we observed a significant decrease in isolates of P. aeruginosa resistant to piperacillin-tazobactam (P = 0.03; P′ = 0.004; P″ = 0.009), and those resistant to imipenem in 2003 (P′ = 0.008). We also noted a significant decrease in A. baumannii isolates resistant to ceftazidime (P′ = 0.01; P″ = 0.0004) and those resistant to imipenem in both 2002 and 2004 (P = 0.03; P″ = 0.04), and a considerable decrease in isolates of Klebsiella pneumoniae producing expanded spectrum betalactamase (ESBL) in 2003 and 2004 (P′ = 0.04; P″ = 6.10⁻⁵). In contrast, we noted an increase in penicillinase-producing isolates of K. pneumoniae, from 6% in 2001 to 16% in 2002 (p = 0.01), 20% in 2003 (P′ = 0.001), and 32% in 2004 (P″ = 10⁻⁶). We concluded that restriction of ceftazidime use was demonstrated to be efficient in reducing antimicrobial resistance, especially to K. pneumoniae ESBL.     

Simultaneous non-parametric confidence intervals for survival probabilities from censored data

In medical studies with censored data Kaplan and Meier's product limit estimator has frequent use as the estimate of the survival function. Simultaneous confidence intervals for the survival function at various time points constitute a useful addition to the analysis. This study compares several such methods. We consider in a simulation investigation two whole curve confidence bands and four methods based on the Bonferroni inequality. The results show that three Bonferroni-type methods are essentially equivalent, all being better than the other methods when the number of time points is small (3 or 5).     

Alterations of mononuclear inflammatory cells, CD4/CD8+ T cells, interleukin 1beta, and tumour necrosis factor alpha in the bronchoalveolar lavage fluid, peripheral blood, and skin of patients with systemic sclerosis

BACKGROUND: Systemic sclerosis (SSc) is a multisystem disease with underlying immune mechanisms. AIMS: To investigate the clinicopathological characteristics of the lesions; immunological alterations in the bronchoalveolar lavage fluid (BALF), peripheral blood, and skin; and correlations between the clinicopathological characteristics and immunological alterations in SSc. MATERIALS/METHODS: Skin biopsies, BALF, and peripheral blood samples were obtained from 19 patients (18 women, one man) with SSc and six age and sex matched healthy controls (HCs). Mononuclear inflammatory cells (MICs), CD4/CD8 cells, tumour necrosis factor alpha (TNFalpha), and interleukin 1beta (IL1-1beta) concentrations were examined in all samples using histological methods, enzyme linked immunosorbent assay, and immunoperoxidase staining. RESULTS: The mean (SD) age of the patients with SSc was 34.8 (2.6) years. Proteinuria, positive rheumatoid factor, and C reactive protein were seen in 15.8%, 26.3%, and 26.3% of patients, respectively. Compared with HCs, there were significantly higher: total MICs (macrophages, lymphocytes), neutrophils, and eosinophils in BALF, blood, and skin (all p<0.05); cytokine concentrations in BALF (TNFalpha, p<0.001; IL-1, p<0.01) and peripheral blood (p<0.01 and p<0.05); and CD8/CD4+ T cells in peripheral blood (p<0.05). Compared with HCs, lesional skin had significantly higher histiocyte cell counts (p<0.05), lower lymphocyte counts (p<0.05), and higher CD4/CD8 ratios (p<0.001). There were significant correlations between cytokine concentrations and CD8+ T cells and forced vital capacity (p<0.001 and p<0.01, respectively). CONCLUSIONS: MICs, CD4/CD8+ cells, and cytokines are altered in SSc. These alterations correlated with the underlying disease process and therefore may have pathogenic, modulatory, and potential prognostic roles in SSc.     

Identification ofSchistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro

Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained fromS. haematobium-infected patients and sex- and agematched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples from 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84 000, 63 000, 57 000, 55 000, 40 000, 30 000, and 28 000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evok in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine.