Validation of a New Aspergillus Real-Time PCR Assay for Direct Detection of Aspergillus and Azole Resistance of Aspergillus fumigatus on Bronchoalveolar Lavage Fluid

Azole resistance in Aspergillus fumigatus is increasingly reported. Here, we describe the validation of the AsperGenius, a new multiplex real-time PCR assay consisting of two multiplex real-time PCRs, one that identifies the clinically relevant Aspergillus species, and one that detects the TR34, L98H, T289A, and Y121F mutations in CYP51A and differentiates susceptible from resistant A. fumigatus strains. The diagnostic performance of the AsperGenius assay was tested on 37 bronchoalveolar lavage (BAL) fluid samples from hematology patients and 40 BAL fluid samples from intensive care unit (ICU) patients using a BAL fluid galactomannan level of ≥1.0 or positive culture as the gold standard for detecting the presence of Aspergillus. In the hematology and ICU groups combined, there were 22 BAL fluid samples from patients with invasive aspergillosis (IA) (2 proven, 9 probable, and 11 nonclassifiable). Nineteen of the 22 BAL fluid samples were positive, according to the gold standard. The optimal cycle threshold value for the presence of Aspergillus was <36. Sixteen of the 19 BAL fluid samples had a positive PCR (2 Aspergillus species and 14 A. fumigatus samples). This resulted in a sensitivity, specificity, and positive and negative predictive values of 88.9%, 89.3%, 72.7%, and 96.2%, respectively, for the hematology group and 80.0%, 93.3%, 80.0%, and 93.3%, respectively, in the ICU group. The CYP51A real-time PCR confirmed 12 wild-type and 2 resistant strains (1 TR34-L98H and 1 TR46-Y121F-T289A mutant). Voriconazole therapy failed for both patients. The AsperGenius multiplex real-time PCR assay allows for sensitive and fast detection of Aspergillus species directly from BAL fluid samples. More importantly, this assay detects and differentiates wild-type from resistant strains, even if BAL fluid cultures remain negative.     

Fasting cholesteryl ester transfer protein concentration is independently associated with the postprandial decrease in high-density lipoprotein cholesterol concentration after fat-rich meals: the Hoorn prandial study

The aim of the study was to test whether fasting or postprandial cholesteryl ester transfer protein (CETP) concentrations are associated with postprandial changes in high-density lipoprotein cholesterol (HDL-c) concentrations after fat-rich or carbohydrate-rich meals. Postmenopausal women (76 with normal glucose metabolism [NGM], 41 with type 2 diabetes mellitus [T2DM], and 38 T2DM women with statin therapy [T2DM-ST]) received 2 consecutive fat-rich or carbohydrate-rich meals on separate occasions. Linear regression analysis was performed to assess the associations of fasting CETP and postprandial changes of CETP with postprandial changes in HDL-c. Mean plasma HDL-c concentrations decreased significantly after the fat-rich meals: 0.18 ± 0.09 mmol/L in NGM, 0.16 ± 0.09 mmol/L in T2DM, and 0.14 ± 0.08 mmol/L in T2DM-ST women. This effect was smaller after using carbohydrate-rich meals: 0.12 ± 0.09 mmol/L in the NGM, 0.12 ± 0.08 mmol/L in the T2DM, and 0.10 ± 0.05 mmol/L in the T2DM-ST study group. Higher fasting but not postprandial CETP concentrations were associated with a larger postprandial decrease in HDL-c (β −0.034; 95% confidence interval, −0.067 to −0.001) after the fat-rich meals. This association was independent of the postprandial increase in triglycerides and similar among the 3 study groups. A high fasting CETP concentration may contribute to the postprandial atherogenic lipoprotein profile in postmenopausal women by decreasing HDL-c after fat-rich meals. This effect is independent from the postprandial increase in triglycerides.     

Ambivalent connections: a qualitative study of the care experiences of non-psychotic chronic patients who are perceived as 'difficult' by professionals

Background

Reliable, valid, and easy-to-administer instruments to identify possible caseness and to provide proxies for clinical diagnoses are needed in epidemiological research on child and adolescent mental health. The aim of this study is to provide further validity data for a parent telephone interview focused on Autism - Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC), for which reliability and preliminary validation data have been previously reported.

Methods

Parents of 91 children clinically diagnosed at a specialized Child Neuropsychiatric Clinic, 366 control children and 319 children for whom clinical diagnoses had been previously assigned were interviewed by the A-TAC over the phone. Interviewers were blind to clinical information. Different scores from the A-TAC were compared to the diagnostic outcome.

Results

Areas under ROC curves for interview scores as predictors of clinical diagnoses were around 0.95 for most disorders, including autism spectrum disorders (ASDs), attention deficit/hyperactivity disorder (AD/HD), tic disorders, developmental coordination disorders (DCD) and learning disorders, indicating excellent screening properties. Screening cut-off scores with sensitivities above 0.90 (0.95 for ASD and AD/HD) were established for most conditions, as well as cut-off scores to identify proxies to clinical diagnoses with specificities above 0.90 (0.95 for ASD and AD/HD).

Conclusions

The previously reported validity of the A-TAC was supported by this larger replication study using broader scales from the A-TAC-items and a larger number of diagnostic categories. Short versions of algorithms worked as well as larger. Different cut-off levels for screening versus identifying proxies for clinical diagnoses are warranted. Data on the validity for mood problems and oppositional defiant/conduct problems are still lacking. Although the A-TAC is principally intended for epidemiological research and general investigations, the instrument may be useful as a tool to collect information in clinical practice as well.     

Review of systematic reviews about the efficacy of non-pharmacological interventions to improve sleep quality in insomnia

Background Insomnia is a very common condition in various populations. Non-pharmacological interventions might offer (safe) alternatives for hypnotics. Aim To evaluate the evidence for efficacy from systematic reviews about non-pharmacological interventions to improve sleep quality in insomnia by a systematic review of systematic reviews and meta-analyses. Search strategy Search strategies were conducted in the Database of Abstracts of Reviews of Effects (2002-July 2008), The Cochrane Database of Systematic Reviews (2000-July 2008) and PubMed (1950-July 2008). Sleep quality was the outcome measure of interest. Selection criteria Systematic reviews about the efficacy of one or more non-pharmacological interventions for insomnia, concerning both adult and elderly populations, were included. Reviews that included studies performed among populations suffering with severe neurological or cognitive impairments or with addictive disorders were excluded. Data analysis Relevant data were extracted. The quality of the reviews found was appraised by using the Overview Quality Assessment Questionnaire. The evidence was appraised and divided into six classes. Results and conclusions Sixteen reviews about 17 interventions were included. Six reviews were of adequate methodological quality. Of these, only one provided an effect size: a moderate effect was found for music-assisted relaxation. Weak evidence indicating a large effect was found for multicomponent cognitive behavioural therapy, progressive muscle relaxation, stimulus control and 'behavioural only'. Weak evidence indicating a moderate effect was found for paradoxical intention. Finally, weak evidence indicating a moderate to large effect was found for relaxation training. Because of the lack of sufficient methodological quality and the lack of calculated effect sizes, most of the included reviews were not suitable for drawing rigorous conclusions about the effect of non-pharmacological interventions on sleep quality in insomniacs. The non-pharmacological treatment of insomnia would benefit from renewed reviews based on a rigorous methodological approach.     

Perceived sleep quality of psychiatric patients

This paper aims at acquiring knowledge about the quality of sleep of adult and elderly psychiatric patients who receive clinical or outpatient nursing care, and identifying key factors in perceiving a sleep problem. To do so, a sample of 1699 psychiatric patients were asked whether they perceived a sleep problem and were invited to fill in the Pittsburgh Sleep Quality Index (PSQI) and additional questions. Five hundred and sixty (33%) questionnaires were returned. As a result, we find that 36% of the patients perceived a sleep problem, while the PSQI assessed 66% of the sample as being 'bad sleepers'. Forty-nine per cent of the respondents used sleep medication one or more times a week. Five items of the PSQI were shown to be predictors of a perceived sleep problem. Four of these are insomnia symptoms, while the fifth is the use of sleep medication. Moreover, the patients who used sleep medication most scored significantly worse on all PSQI components than patients who used sleep medication less than once a week. In conclusion, many psychiatric patients perceive a sleep problem and all nurses could be confronted not only with the night-time consequences of this, but also with daytime consequences. Therefore, sleep problems must not be viewed as an isolated problem but must be seen in relation with social functioning.     

The lifetime prevalence of traumatic events and posttraumatic stress disorder in the Netherlands

Little information exists on the lifetime prevalence of traumatic events and posttraumatic stress disorder (PTSD) in the general population of the Netherlands. A national representative sample of 1087 adults aged 18 to 80 years was selected using random digit dialing and then surveyed by telephone using the Composite International Diagnostic Interview (CIDI) to determine the prevalence of trauma and DSM‐IV PTSD. The lifetime prevalence of any potential trauma was 80.7%, and the lifetime prevalence of PTSD was 7.4%. Women and younger persons showed higher risk of PTSD. It was concluded that PTSD is a fairly common disorder and exposure to trauma is high throughout the population. Unexpectedly, prevalence rates resemble those found in the United States and are higher than in several other European countries.