Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

Long-term azithromycin use is not associated with QT prolongation in children with cystic fibrosis

Chronic Azithromycin (AZM) is a common treatment for lung infection. Among adults at risk of cardiac events, AZM use has been associated with cardiovascular harm. We assessed cardiovascular safety of AZM among children with CF, as a secondary analysis of a placebo-controlled, clinical trial, in which study drug was taken thrice-weekly for a planned 18 months. Safety assessments using electrocardiogram (ECG) occurred at study enrollment, and then after 3 weeks and 18 months of participation. Among 221 study participants with a median of 18 months follow-up, increased corrected QT interval (QTc) of ≥30 msec was rare, at 3.4 occurrences per 100 person-years; and incidence of QTc prolongation was no higher in the AZM arm than the placebo arm (1.8 versus 5.4 per 100 person-years). No persons experienced QTc intervals above 500 msec. Long-term chronic AZM use was not associated with increased QT prolongation.     

Expanding allelic and phenotypic spectrum of ZC4H2-related disorder: A novel hypomorphic variant and high prevalence of tethered cord

ZC4H2 (MIM# 300897) is a nuclear factor involved in various cellular processes including proliferation and differentiation of neural stem cells, ventral spinal patterning and osteogenic and myogenic processes. Pathogenic variants in ZC4H2 have been associated with Wieacker-Wolff syndrome (MIM# 314580), an X-linked neurodevelopmental disorder characterized by arthrogryposis, development delay, hypotonia, feeding difficulties, poor growth, skeletal abnormalities, and dysmorphic features. Zebrafish zc4h2 null mutants recapitulated the human phenotype, showed complete loss of vsx2 expression in brain, and exhibited abnormal swimming and balance problems. Here we report 7 new patients (four males and three females) with ZC4H2-related disorder from six unrelated families. Four of the 6 ZC4H2 variants are novel: three missense variants, designated as c.142T>A (p.Tyr48Asn), c.558G>A (p.Met186Ile) and c.602C>T (p.Pro201Leu), and a nonsense variant, c.618C>A (p.Cys206*). Two variants were previously reported : a nonsense variant c.199C>T (p.Arg67*) and a splice site variant (c.225+5G>A). Five patients were on the severe spectrum of clinical findings, two of whom had early death. The male patient harboring the p.Met186Ile variant and the female patient that carries the p.Pro201Leu variant have a relatively mild phenotype. Of note, 4/7 patients had a tethered cord that required a surgical repair. We also demonstrate and discuss previously under-recognized phenotypic features including sleep apnea, arrhythmia, hypoglycemia, and unexpected early death. To study the effect of the missense variants, we performed microinjection of human ZC4H2 wild-type or variant mRNAs into zc4h2 null mutant zebrafish embryos. The p.Met186Ile mRNA variant was able to partially rescue vsx2 expression while p.Tyr48Asn and p.Pro201Leu mRNA variants were not. However, swimming and balance problems could not be rescued by any of these variants. These results suggest that the p.Met186Ile is a hypomorphic allele. Our work expands the genotypes and phenotypes associated with ZC4H2-related disorder and demonstrates that the zebrafish system is a reliable method to determine the pathogenicity of ZC4H2 variants.     

VIOLENT BEHAVIOUR IN PYSCHIATRIC INPATIENTS

A study of violent behaviour among psychiatric inpatients in a large general hospital is presented. Over the study period of one year a total of 36 incidents of violence involving 26 patients were recorded. Schizophrenia was the most common diagnosis among assailants. Fellow patients were the main victims. Incidence of serious violence was low. Most incidents occurred in the night hours, from inmates of acute wards and mostly without any provocation.KEY WORDS: Violent behaviour, Psychiatric patients     

Use of Professional Associate Ratings to Assess the Performance of Practicing Physicians: Past, Present, Future

The American Board of Family Practice (ABFP) is developing a computer-based testing system that will create realistic clinical encounters using an adaptation of an item generation process. Simulated patients' entire lives will be stochastically produced from a knowledge base, with constraints applied to prevent implausible simulations. The constraint mechanisms include knowledge acquisition decisions about grouping closely related medical concepts and widespread use of Bayesian networks to manage dependencies between concepts. Bayesian networks and fuzzy definitions provide stochastic variability between simulations produced from the same data. Examinees will interact with these patients using a large and stable set of queries and interventions. Multiple management plans associated with patient simulations provide a framework for scoring performance. All major components, including Health States, history generating "Lead To" objects, and Plans are reusable and often substitutable. Although initial knowledge acquisition demands are enormous, the system has good potential for low cost maintenance of content areas, and economies of scale as simulations and components are reused.     

On the use of survival analysis techniques to estimate medical care costs.

Measurement of treatment costs is important in the evaluation of medical interventions. Accurate cost estimation is problematic, when cost records are incomplete. Methods from the survival analysis literature have been proposed for estimating costs using available data. In this article, we clarify assumptions necessary for validity of these techniques. We demonstrate how assumptions needed for valid survival analysis may be violated when these methods are applied to cost estimation. Our observations are confirmed through simulations and empirical data analysis. We conclude that survival analysis approaches are not generally appropriate for the analysis of medical costs and review several valid alternatives.     

Spatio-temporal progression of the AEP P300 component using the cortical imaging technique

Summary The cortical imaging technique (CIT), a mathematical method for simulating the potential fields on the surface of the brain, was used to analyze the spatio-temporal progression of the AEP P300 component (as well as the preceding and subsequent N2a and N3 components) from thirty normal adult subjects recorded in a standard oddball paradigm. Comparisons were made between the progressions of the endogenous event-related cognitive potentials and the exogenous stimulus-dependent potentials (Nl component). Cortical imaging results suggest that different and multiple generator sites are involved in the production of exogenous and endogenous evoked responses. We particularly note the asymmetric development of the P300 component and the apparent anterior generator sites for the N2a component. This last result is interesting because the N2a precedes the P300 component and supports an earlier frontal contribution.