Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): Data from a randomized-withdrawal,placebo-controlled maintenance study

Background

This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD.

Methods

Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4–8 weeks) and a 12–18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI).

Results

In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: −0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score ‘family life/home responsibilities’ (−0.13 vs. 0.32; p=0.011), but not ‘social life’ (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ‘days lost’ (−0.05 vs. 0.11; p=0.027), but not ‘work/school’ (−0.10 vs. 0.29; p=0.051) or ‘days underproductive’ (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).

Limitations

Lack of active-comparator arm, exclusion of patients with comorbid depression.

Conclusions

In patients with GAD, long-term treatment with quetiapine XR (50–300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.     

Presence of enteroviruses in recreational water in Wuhan,China

Contaminated recreational waters pose a public health concern, as the potential for waterborne diseases exists in water contaminated with human fecal waste. Worldwide, bacterial indicators such as Escherichia coli, enterococci, and total and fecal coliform are used as indicators of water quality. However, enteric viruses also present a public health concern and their presence cannot always be determined based on bacterial indicators. This study explores the use of molecular detection methods of enteric viruses as indicators of fecal contamination. Four viruses, enterovirus, norovirus genogroups I and II, and male-specific FRNA coliphage, were tested in this study. Highly sensitive RT-PCR methods developed at the University of Hawaii at Manoa were utilized to evaluate environmental samples collected from three lakes in Wuhan, Hubei Province, China. Sixteen of twenty-five sites tested positive for at least one virus. Enterovirus was the most commonly detected virus, followed by norovirus genogroup I. These findings support the use of molecular detection methods to test for enteric virus presence in recreational freshwater sources in China as alternative water quality indicators, and utilize recently developed, highly sensitive methods of detection of these viruses. In addition, these findings suggest that there is substantial fecal contamination of the three lakes tested in this study.     

Association of G-174C Polymorphism of the Interleukin-6 Gene Promoter with Graves' Ophthalmopathy

Interleukin-6 (IL-6) may play an important role in the pathogenesis of Graves' ophthalmopathy (GO). The aim of this study was to analyze the association of IL-6 gene promoter polymorphism, at position -174 (G→C, termed as G-174C), which may affect IL-6 production, with the development of GO. The G-174C polymorphism was determined in 279 Polish-Caucasian patients with Graves' disease (GD), of which 108 had clinically evident ophthalmopathy (NOSPECS class III or higher) and 186 healthy Polish adults. In patients with GD, the frequencies of the C allele (45 vs 42%; P=0.35) and C/C genotype (20 vs 15%; P=0.13) were not significantly different compared to controls. Subdividing patients with GD for the presence of eye disease revealed that the C allele (44 vs 45%; P=0.76) and C/C genotype (20 vs 20%; P=0.92) were equally distributed in patients with or without ophthalmopathy. There was also no association between the G-174C polymorphism and the severity of eye changes. Finally, IL-6 genotypes were not associated with laboratory findings (thyroid volume, serum IL-6 and thyroid autoantibodies levels) in patients with GD at diagnosis. Our results suggest that G-174C polymorphism of the IL-6 gene does not contribute to the development and severity of GO.     

Image Quality in Real-Time Teleultrasound of Infant Hip Exam Over Low-Bandwidth Internet Links: a Transatlantic Feasibility Study

Evolution of communication systems, especially internet-based technologies, has probably affected Radiology more than any other medical specialty. Tremendous increase in internet bandwidth has enabled a true revolution in image transmission and easy remote viewing of the static images and real-time video stream. Previous reports of real-time telesonography, such as the ones developed for emergency situations and humanitarian work, rely on high compressions of images utilized by remote sonologist to guide and supervise the unexperienced examiner. We believe that remote sonology could be also utilized in teleultrasound exam of infant hip. We tested feasibility of a low-cost teleultrasound system for infant hip and performed data analysis on the transmitted and original images. Transmission of data was accomplished with Remote Ultrasound (RU), a software package specifically designed for teleultrasound transmission through limited internet bandwidth. While image analysis of image pairs revealed statistically significant loss of information, panel evaluation failed to recognize any clinical difference between the original saved and transmitted still images.     

Optimisation of radiographic acquisition parameters for direct digital radiography: A systematic review

IntroductionThe objective of this systematic review was to uncover and synthesise all available literature regarding appropriate acquisition parameters for direct digital radiography. It sought to either confirm current practices as optimal, or to uncover practices that may produce more optimised results.MethodsA comprehensive search of published and unpublished literature was undertaken to find studies that evaluated how adjustment of different acquisition parameters affected subjective image quality and patient radiation dose. Eight hundred and fifty-eight studies were retrieved for title and abstract screening. Eighty-nine studies were retrieved for full-text screening, and 23 were included for review and methodological quality screening.ResultsNarrative synthesis of the 23 included studies revealed limited evidence to guide any potential change or acceptance of currently accepted best practice. Meta-analysis was unable to be performed for any of the included studies due to high levels of methodological heterogeneity. A key finding of this review was that the goals of optimisation research varied greatly across the included studies.ConclusionSignificant methodological heterogeneity in the included studies limited the number of clinically relevant findings that would give evidence to an acceptance of, or suggest changes to, currently accepted best practice. Improving consistency in approach across future works of technique optimisation will ensure future systematic reviews will be able to provide strong evidence and meta-analysis will be able to be performed.Implications for clinical practiceThis review highlights that in the literature, studies of optimisation of radiographic acquisition parameters have varying goals. This methodological heterogeneity limits the applicability of systematic reviews and precludes the use of meta-analysis. The authors recommend that a framework for optimisation research be produced as a priority to help improve homogeneity in future research.     

Effective treatments for FGF12-related early-onset epileptic encephalopathies patients

BackgroundFGF12 (FHF1) gene encodes voltage-gated sodium channel (Nav)-binding protein fibroblast growth factor homologous factor 1, which could cause seizures by regulating voltage dependence of Nav fast inactivation and neuron excitability. The most common pathogenic variant FGF12 c.341G > A related early-onset epileptic encephalopathies (EOEE) was characterized by intractable seizures and developmental disabilities.ResultsUsing whole exome sequencing, a de novo hotspot variant c.341G > A (NM_021032.4) of FGF12 was identified in three unrelated EOEE probands. All probands were seizure free after a combination treatment of valproic acid (VPA) and topiramate (TPM). The motor and cognitive skills in two probands were improved due to the early and effective treatment. In order to compare the effectiveness of different treatment strategies for the disease, a review of treatments for FGF12-related epilepsy was made.ConclusionWe reported three FGF12 c.341G > A related EOEE patients responded well to a combination antiepileptic therapy of VPA and TPM. The current study is the first to describe the combination therapy of VPA and TPM in FGF12 c.341G > A related EOEE patients. This study may contribute to future medication consultation for intractable epilepsy with FGF12 hotspot variants.     

Factors that influence parents’ experiences with results disclosure after newborn screening identifies genetic carrier status for cystic fibrosis or sickle cell hemoglobinopathy

Objective

Newborn screening (NBS) identifies genetic carriers for sickle cell hemoglobinopathy and cystic fibrosis. We aimed to identify factors during initial NBS carrier results disclosure by primary care providers (PCPs) that influenced parents’ experiences and reactions.

Methods

Open-ended responses from telephone interviews with 270 parents of carriers were analyzed using mixed-methods. Conventional content analysis identified influential factors; chi-square tests analyzed relationships between factors and parent-reported reactions.

Results

Parents reported positive (35%) or negative (31%) reactions to results disclosure. Parents’ experiences were influenced by specific factors: content messages (72%), PCP traits (47%), and aspects of the setting (30%). Including at least one of five specific content messages was associated (p < 0.05) with positive parental reactions; omitting at least one of four specific content messages was associated (p < 0.05) with negative parental reactions. Parents reported positive reactions when PCPs avoided jargon or were perceived as calm. Parents reported negative reactions to jargon usage and results disclosure by voicemail.

Conclusion

Parents identified aspects of PCP communication which influenced their reactions and results disclosure experiences.

Practice implications

Our findings suggest ways PCPs may improve communication of carrier results. PCPs should provide specific content messages and consider how their actions, characteristics, and setting can influence parental reactions.     

Hedging,knowledge and interaction: Doctors’ and clients’ talk about medical information and client experiences in genetic counseling

Objectives

The article starts from the observation that professionals in genetic counseling deploy the strategy of ‘hedging’. It shows how hedging is used in a particular sequential position: doctors’ responses to clients’ presentations of personal information during information delivery sequences.

Methods

The data consist of video-recorded sessions of genetic counseling. The methodology is based on ethnomethodological conversation analysis. The analysis identifies interactional patterns in the counseling sessions.

Results

In their responses doctors display an orientation to different access to different kinds of knowledge. In particular, the doctors tread carefully when commenting on the situation of a particular client vis-á-vis the symptoms and prognosis of genetic conditions. Furthermore, the article shows that the doctors’ responses and hedging devices in them are fitted to the form and function of the clients’ presentations of personal experience.

Conclusion

While the focus of the article is narrow in that it concentrates on one type of an interactional sequence, its strength is that it shows how the doctor's talk can be intertwined with the client's contributions.

Practice implications

The results make it possible for genetic counselors to identify an interactional task they recurrently face and reflect on alternative ways of responding to it.     

Preface and Overview: Genetics of SLE; A sine qua non for identification

Clinical manifestations of systemic lupus erythematosus (SLE) are extremely diverse and variable, mainly because SLE is a multi-factorial disease. Variable combinations of contributing genes at multiple loci in individual patients probably result in diverse disease phenotypes. Genes that predispose to SLE are undoubtedly related to key events in pathogenesis, and may involve a variety of genes in immune system. These genes are currently unidentified, mostly because of the complexity of multi-factorial inheritance. Recently, the application of the polymerase chain reaction and the availability of maps of microsatellites have facilitated a genome-wide scan to define the number and locations of genes for complex traits. However, extensive genetic heterogeneities and polymorphisms and complex modes of inheritance of disease phenotypes have delayed completion of a genome-wide analysis of susceptibility loci for human SLE. Since many SLE-susceptibility genes show low penetrance, several hundred affected sibpairs are assumed to be necessary to show linkages for many of the contributing loci. In this respect, studies of polymorphisms and functions of candidate genes suggested based on studies on murine models may contribute to studies on SLE patients and their relatives. Major genetic loci have been mostly identified in SLE-prone mouse strains. Nevertheless, identity of natures, functions and roles in the pathogenesis of SLE remains undetermined. Considering the possibility of clustering of susceptibility loci in a particular chromosomal interval, the final goal for identification of susceptibility genes will largely depend on the generation of mutant SLE-prone mice with homologous recombination of the potential target gene. Extensive reviews collected here are expected to form the basis for identification of target genes and for clarification of the genetic mechanisms underlying SLE.