Parametric hazard rate models for long-term sickness absence

PURPOSE: In research on the time to onset of sickness absence and the duration of sickness absence episodes, Cox proportional hazard models are in common use. However, parametric models are to be preferred when time in itself is considered as independent variable. This study compares parametric hazard rate models for the onset of long-term sickness absence and return to work. METHOD: Prospective cohort study on sickness absence with four follow-up years of 53,830 employees working in the private sector in the Netherlands. The time to onset of long-term (>6 weeks) sickness absence and return to work were modelled by parametric hazard rate models. RESULTS: The exponential parametric model with a constant hazard rate most accurately described the time to onset of long-term sickness absence. Gompertz-Makeham models with monotonically declining hazard rates best described return to work. CONCLUSIONS: Parametric models offer more possibilities than commonly used models for time-dependent processes as sickness absence and return to work. However, the advantages of parametric models above Cox models apply mainly for return to work and less for onset of long-term sickness absence

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy

British Valued Life Activities Scale [British VLAs]

Background The Valued Life Activities Scale (VLAs) measures difficulty in daily activities and social participation. With various versions involving a different number of items, we have linguistically and culturally adopted the full VLAs (33-items) and psychometrically tested it in adults with rheumatic and musculoskeletal diseases in the United Kingdom. Methods Participants with Rheumatoid Arthritis, Ankylosing Spondylitis, Chronic Pain/ Fibromyalgia, Chronic Hand/ Upper Limb Conditions, Osteoarthritis, Systemic Lupus, Systemic Sclerosis and Primary Sjogren’s Syndrome were recruited from out-patient clinics in National Health Service Hospitals, General Practice and patient organisations in the UK. Phase1 involved linguistic and cultural adaptation: forward translation to British English; synthesis; expert panel review and cognitive debriefing interviews. In Phase2 participants completed postal questionnaires to assess internal construct validity using (i) Confirmatory Factor Analysis (CFA) (ii) Mokken scaling and (iii) Rasch model. Results Responders (n = 1544) had mean age of 59 years (SD13.3) and 77.2% women. A CFA failed to support a total score from the 33-items (Chi Square 3552:df 464: p < 0.0001). Mokken scaling indicated a strong non-parametric association between items. Fit to the Rasch model indicated that the VLAs was characterised by multidimensionality and item misfit, which may have been influenced by clusters of residual item correlations. An item banking approach resolved a 25-item calibrated set whose application could accommodate the ‘does not apply to me’ response option. Conclusions The UK version of the VLAs failed to satisfy classical and modern psychometric standards for complete item sets. However, as the scale is not usually applied in complete format, an item bank approach calibrated 25 items with fit to the Rasch model. Suitable Computer Adaptive Testing (CAT) software could implement the item set, giving patients the choice of whether an item applies to them, or not

Adaptive Evolution of the Myo6 Gene in Old World Fruit Bats (Family: Pteropodidae)

PMCID: PMC3631194This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Recurrence of Medically Certified Sickness Absence According to Diagnosis: A Sickness Absence Register Study

Introduction Sickness absence is a major public health problem. Research on sickness absence focuses on interventions aimed at expediting return to work. However, we need to know more about sustaining employees at work after return to work. Therefore, this study investigated the recurrence of sickness absence according to diagnosis. Methods We analyzed the registered sickness absence data of 137,172 employees working for the Dutch Post and Telecom. Episodes of sickness absence were medically certified, according to the ICD-10 classification of diseases, by an occupational physician. The incidence density (ID) and recurrence density (RD) of medically certified absences were calculated per 1,000 person-years in each ICD-10 category. Results Sickness absence due to musculoskeletal disorders had the highest recurrence (RD = 118.7 per 1,000 person-years), followed by recurrence of sickness absence due to mental disorders (RD = 80.4 per 1,000 person-years). The median time to recurrent sickness absence due to musculoskeletal disorders was 409 days after the index episode. Recurrences of sickness absence due to musculoskeletal disorders accounted for 37% of the total number of recurrent sickness absence days. For recurrences of sickness absence due to mental disorders this was 328 days and 21%, respectively. Unskilled employees with a short duration (<5 years) of employment had a higher risk of recurrent sickness absence. Conclusions Interventions to expedite return to work of employees sick-listed due to musculoskeletal or mental disorders should also aim at reducing recurrence of sickness absence in order to sustain employees at work

Better assessment of physical function: item improvement is neglected but essential

INTRODUCTION: Physical function is a key component of patient-reported outcome (PRO) assessment in rheumatology. Modern psychometric methods, such as Item Response Theory (IRT) and Computerized Adaptive Testing, can materially improve measurement precision at the item level. We present the qualitative and quantitative item-evaluation process for developing the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function item bank. METHODS: The process was stepwise: we searched extensively to identify extant Physical Function items and then classified and selectively reduced the item pool. We evaluated retained items for content, clarity, relevance and comprehension, reading level, and translation ease by experts and patient surveys, focus groups, and cognitive interviews. We then assessed items by using classic test theory and IRT, used confirmatory factor analyses to estimate item parameters, and graded response modeling for parameter estimation. We retained the 20 Legacy (original) Health Assessment Questionnaire Disability Index (HAQ-DI) and the 10 SF-36\u27s PF-10 items for comparison. Subjects were from rheumatoid arthritis, osteoarthritis, and healthy aging cohorts (n = 1,100) and a national Internet sample of 21,133 subjects. RESULTS: We identified 1,860 items. After qualitative and quantitative evaluation, 124 newly developed PROMIS items composed the PROMIS item bank, which included revised Legacy items with good fit that met IRT model assumptions. Results showed that the clearest and best-understood items were simple, in the present tense, and straightforward. Basic tasks (like dressing) were more relevant and important versus complex ones (like dancing). Revised HAQ-DI and PF-10 items with five response options had higher item-information content than did comparable original Legacy items with fewer response options. IRT analyses showed that the Physical Function domain satisfied general criteria for unidimensionality with one-, two-, three-, and four-factor models having comparable model fits. Correlations between factors in the test data sets were \u3e 0.90. CONCLUSIONS: Item improvement must underlie attempts to improve outcome assessment. The clear, personally important and relevant, ability-framed items in the PROMIS Physical Function item bank perform well in PRO assessment. They will benefit from further study and application in a wider variety of rheumatic diseases in diverse clinical groups, including those at the extremes of physical functioning, and in different administration modes

Psychosocial work conditions and registered sickness absence: a 3-year prospective cohort study among office employees

Purpose To investigate associations between a wide variety of psychosocial work conditions and sickness absence in a medium-sized company. Methods Prospective cohort study of 395 employees working in an insurance office. Self-reported psychosocial work conditions were measured by questionnaire in January 2002 and linked to registered sickness absence in the period January 2002 to December 2004 adjusting for earlier sick leave and psychological distress. Results The questionnaires of 244 employees were eligible for analysis. Decision authority and co-worker support were associated with sickness absence days, but their associations with sickness absence episodes were not significant. Role clarity was associated with the number of sickness absence days, but only with the number of short sickness absence episodes in women. Conclusions The wide variety of investigated psychosocial work conditions contributed little to the explanation of sickness absence in the medium-sized insurance office

Can work ability explain the social gradient in sickness absence: a study of a general population in Sweden

<p>Abstract</p> <p>Background</p> <p>Understanding the reasons for the social gradient in sickness absence might provide an opportunity to reduce the general rates of sickness absence. The complete explanation for this social gradient still remains unclear and there is a need for studies using randomized working population samples. The main aim of the present study was to investigate if self-reported work ability could explain the association between low socioeconomic position and belonging to a sample of new cases of sick-listed employees.</p> <p>Methods</p> <p>The two study samples consisted of a randomized working population (n = 2,763) and a sample of new cases of sick-listed employees (n = 3,044), 19-64 years old. Both samples were drawn from the same randomized general population. Socioeconomic status was measured with occupational position and physical and mental work ability was measured with two items extracted from the work ability index.</p> <p>Results</p> <p>There was an association between lower socioeconomic status and belonging to the sick-listed sample among both women and men. In men the crude Odds ratios increased for each downwards step in socioeconomic status, OR 1.32 (95% CI 0.98-1.78), OR 1.53 (1.05-2.24), OR 2.80 (2.11-3.72), and OR 2.98 (2.27-3.90). Among women this gradient was not as pronounced. Physical work ability constituted the strongest explanatory factor explaining the total association between socioeconomic status and being sick-listed in women. However, among men, the association between skilled non-manual, OR 2.07 (1.54-2.78), and non-skilled manual, OR 2.03 (1.53-2.71) positions in relation to being sick-listed remained. The explanatory effect of mental work ability was small. Surprisingly, even in the sick-listed sample most respondents had high mental and physical work ability.</p> <p>Conclusions</p> <p>These results suggest that physical work ability may be an important key in explaining the social gradient in sickness absence, particularly in women. Hence, it is possible that the factors associated with the social gradient in sickness absence may differ, to some extent, between women and men.</p

The Aarhus red giants challenge: II. Stellar oscillations in the red giant branch phase

Contact. The large quantity of high-quality asteroseismic data that have been obtained from space-based photometric missions and the accuracy of the resulting frequencies motivate a careful consideration of the accuracy of computed oscillation frequencies of stellar models, when applied as diagnostics of the model properties. Aims. Based on models of red-giant stars that have been independently calculated using different stellar evolution codes, we investigate the extent to which the differences in the model calculation affect the model oscillation frequencies and other asteroseismic diagnostics. Methods. For each of the models, which cover four different masses and different evolution stages on the red-giant branch, we computed full sets of low-degree oscillation frequencies using a single pulsation code and, from these frequencies, typical asteroseismic diagnostics. In addition, we carried out preliminary analyses to relate differences in the oscillation properties to the corresponding model differences. Results. In general, the differences in asteroseismic properties between the different models greatly exceed the observational precision of these properties. This is particularly true for the nonradial modes whose mixed acoustic and gravity-wave character makes them sensitive to the structure of the deep stellar interior and, hence, to details of their evolution. In some cases, identifying these differences led to improvements in the final models presented here and in Paper I; here we illustrate particular examples of this. Conclusions. Further improvements in stellar modelling are required in order fully to utilise the observational accuracy to probe intrinsic limitations in the modelling and improve our understanding of stellar internal physics. However, our analysis of the frequency differences and their relation to stellar internal properties provides a striking illustration of the potential, in particular, of the mixed modes of red-giant stars for the diagnostics of stellar interiors. © ESO 2020