Standardization of Nucleic Acid Tests:The Approach of the World Health Organization

The first World Health Organization (WHO) international standards (ISs) for nucleic acid amplification techniques were established two decades ago, with the initial focus on blood screening for three major viral targets, i.e., hepatitis C virus, hepatitis B virus, and human immunodeficiency virus 1. These reference materials have subsequently found utility in the diagnosis and monitoring of a wide range of infectious diseases in clinical microbiology laboratories worldwide. WHO collaborating centers develop ISs and coordinate international studies for their evaluation. The WHO Expert Committee on Biological Standardization is responsible for the endorsement of new standardization projects and the establishment of new and replacement ISs. Potencies of ISs are defined in international units (IU); the reporting in IU for assays calibrated with an IS (or secondary standards traceable to the IS) facilitates comparability of results for different assays and determination of assay parameters such as analytical sensitivities

Patient satisfaction with anaesthesia care: development of a psychometric questionnaire and benchmarking among six hospitals in Switzerland and Austria†‡

Background. We describe the development and comparison of a psychometric questionnaire on patient satisfaction with anaesthesia care among six hospitals. Methods. We used a rigorous protocol: generation of items, construction of the pilot questionnaire, pilot study, statistical analysis (construct validity, factor analysis, reliability analysis), compilation of the final questionnaire, main study, repeated analysis of construct validity and reliability. We compared the mean total problem score and the scores for the dimensions: ‘Information/Involvement in decision‐making', and ‘Continuity of personal care by anaesthetist'. The influence of potential confounding variables was tested (multiple linear regression). Results. The average problem score from all hospitals was 18.6%. Most problems are mentioned in the dimensions ‘Information/Involvement in decision‐making' (mean problem score: 30.9%) and ‘Continuity of personal care by anaesthetist' (mean problem score: 32.2%). The overall assessment of the quality of anaesthesia care was good to excellent in 98.7% of cases. The most important dimension was ‘Information/Involvement in decision‐making'. The mean total problem score was significantly lower for two hospitals than the total mean for all hospitals (significantly higher at two hospitals) (P<0.05). Amongst the confounding variables considered, age, sex, subjective state of health, type of anaesthesia and level of education had an influence on the total problem score and the two dimensions mentioned. There were only marginal differences with and without the influence of the confounding variables for the different hospitals. Conclusions. A psychometric questionnaire on patient satisfaction with anaesthesia care must cover areas such as patient information, involvement in decision‐making, and contact with the anaesthetist. The assessment using summed scores for dimensions is more informative than a global summed rating. There were significant differences between hospitals. Moreover, the high problem scores indicate a great potential for improvement at all hospitals. Br J Anaesth 2002; 89: 863-7

Musculoskeletal symptoms of the upper extremities and the neck: A cross-sectional study on prevalence and symptom-predicting factors at visual display terminal (VDT) workstations

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine the prevalence and the predictors of musculoskeletal symptoms in the upper extremities and neck at visual display terminal (VDT) workstations.</p> <p>Methods</p> <p>In a cross-sectional study 1,065 employees working at VDT > 1 h/d completed a standardised questionnaire. Workstation conditions were documented in a standardised checklist, and a subgroup of 82 employees underwent a physical examination.</p> <p>Results</p> <p>Using the Nordic Questionnaire, the 12-month prevalence of symptoms of the neck, shoulder region, hand/wrist, or elbow/lower arm was 55%, 38%, 21%, and 15% respectively. The duration of VDT work had a significant impact on the frequency of neck symptoms in employees performing such work > 6 h/d.</p> <p>Conclusion</p> <p>With regard to musculoskeletal symptoms of the upper extremities, preventive measures at VDT workstations should be focused on neck and shoulder symptoms (e.g. ergonomic measures, breaks to avoid sitting over long periods).</p

A Gammaherpesviral Internal Repeat Contributes to Latency Amplification

BACKGROUND: Gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. The genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood. METHODOLOGY/PRINCIPAL FINDINGS: We used infection of laboratory mice with murine gammaherpesvirus 68 (MHV-68) to explore the biological role of the 40 bp internal repeat of MHV-68. We constructed several mutant viruses partially or completely lacking this repeat. Both in vitro and in vivo, the loss of the repeat did not substantially affect lytic replication of the mutant viruses. However, the extent of splenomegaly, which is associated with the establishment of latency, and the number of ex vivo reactivating and genome positive splenocytes were reduced. Since the 40 bp repeat is part of the hypothetical open reading frame (ORF) M6, it might function as part of M6 or as an independent structure. To differentiate between these two possibilities, we constructed an N-terminal M6STOP mutant, leaving the repeat structure intact but rendering ORF M6 unfunctional. Disruption of ORF M6 did neither affect lytic nor latent infection. In contrast to the situation in lytically infected NIH3T3 cells, the expression of the latency-associated genes K3 and ORF72 was reduced in the latently infected murine B cell line Ag8 in the absence of the 40 bp repeat. CONCLUSIONS/SIGNIFICANCE: These data suggest that the 40 bp repeat contributes to latency amplification and might be involved in the regulation of viral gene expression

Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

BACKGROUND: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. OBJECTIVES: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. METHODS: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. RESULTS: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. CONCLUSION: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials

Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network.

OBJECTIVE: To investigate whether herpes simplex virus type 1 (HSV-1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). METHODS: Among two subsets of the DIAN cohort (age range 19.6-66.6 years; median follow-up 3.0 years) we examined (i) rate of cognitive decline (N = 164) using change in mini-mental state examination (MMSE) score, (ii) rate of whole brain atrophy (N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV-1 antibodies were assayed in baseline sera collected from 2009-2015. Linear mixed-effects models were used to compare outcomes by HSV-1 seropositivity and high HSV-1 IgG titres/IgM status. RESULTS: There was no association between baseline HSV-1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV-1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope - 0.365, 95% CI: -0.958 to -0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV-1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV-1 seronegative. Among mutation-negative individuals, no differences were seen by HSV-1. Stratifying by APOE4 status yielded inconsistent results. INTERPRETATION: We found no evidence for a major role of HSV-1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early-onset AD

When coders are reliable: the application of three measures to assess inter-rater reliability/agreement with doctor-patient communication data coded with the VR-CoDES.

Objective To investigate whether different measures of inter-rater reliability will compute similar estimates with nominal data commonly encountered in communication studies. To make recommendations how reliability should be computed and described for communication coding instruments. Methods The raw data from an inter-rater study with three coders were analysed with; Cohen's κ, sensitivity and specificity measures, Fleiss's multirater κj, and an intraclass correlation coefficient (ICC). Results Minor differences were found between Cohen's κ and an ICC model across paired data (largest margin = 0.01). There were negligible differences between the multirater estimates e.g. κj (0.52) and ICC (0.53). Sensitivity analyses were in general agreement with the multirater estimates. Conclusion It is more practical to analyse nominal data with >2 raters with an appropriate model ICC for inter-rater studies, and little difference exists between Cohen's κ or an ICC. Practice implication Alternatives to Cohen's κ are readily available, but researchers need to be aware of the different ICC definitions. An ICC model should be fully described in reports. Investigators are encouraged to supply confidence limits with inter-rater data, and to revisit guidance regarding the relative strengths of agreement of reliability coefficients