Paper and electronic versions of HM-PRO, a novel patient-reported outcome measure for hematology: an equivalence study.

© 2019 Goswami, Oliva, Ionova et al.Aim:To determine measurement equivalence of paper and electronic application of the hematologi-cal malignancy-patient-reported outcome (HM-PRO), a specific measure for the evaluation of patient-reported outcomes in HMs.Patients & methods:Following International Society of Pharmacoeconomicsand Outcomes Research ePRO Good Research Practice Task Force guidelines, a total of 193 adult patientswith different HMs were recruited into a multicenter prospective study. The paper and the electronic ver-sion of the instrument were completed in the outpatient clinics in a randomized crossover design with a30-min time interval to minimize the learning effect. Those who completed the paper version first, com-pleted the electronic version after 30 min and vice versa. Instrument version and order effects were testedon total score of the two parts of the HM-PRO (Part A: quality of life and Part B: signs & symptoms) in atwo-way ANOVA with patients as random effects. Intraclass correlation coefficients (95% CI) and Spear-man’s rank correlation coefficients were used to evaluate test–retest reliability and reproducibility. Theeffects of instrument version and order were tested on total score of the two parts of HM-PRO.Results:The questionnaire version and administration order effects were not significant at the 5% level. Therewere no interactions found between these two factors for HM-PRO (Part A [quality of life]; p=0.95); and(part B [signs and symptoms]; p=0.72]. Spearman’s rank correlation coefficients were greater than 0.9, andintraclass correlation coefficients ranged from 0.94 to 0.98; furthermore, the scores were not statisticallydifferent between the two versions, showing acceptable reliability indexes. Noteworthy, the differencebetween the completion time for both paper (mean=6:38 min) and electronic version (mean=7:29 min)was not statistically significant (n=100; p=0.11). Patients did not report any difficulty in completing theelectronic version during cognitive interviews and were able to understand and respond spontaneously.Conclusion:Measurement equivalence has been demonstrated for the paper and electronic applicationof the HM-PRO.Peer reviewe

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u

Low-smoke chulha in Indian slums: study protocol for a randomised controlled trial

Background Biomass fuel is used as a primary cooking source by more than half of the world’s population, contributing to a high burden of disease. Although cleaner fuels are available, some households continue using solid fuels because of financial constraints and absence of infrastructure, especially in non-notified slums. The present study documents a randomised controlled study investigating the efficacy of improved cookstove on the personal exposure to air pollution and the respiratory health of women and children in an Indian slum. The improved cookstove was based on co-creation of a low-smoke chulha with local communities in order to support adaption and sustained uptake. Methods The study will be conducted in a non-notified slum called Ashrayanagar in Bangalore, India. The study design will be a 1:1 randomised controlled intervention trial, including 250 households. The intervention group will receive an improved cookstove (low-smoke chulha) and the control group will continue using either the traditional cookstove (chulha) or a combination of the traditional stove and the kerosene/diesel stove. Follow-up time is 1 year. Outcomes include change in lung function (FEV1/FVC), incidence of pneumonia, change in personal PM2.5 and CO exposure, incidence of respiratory symptoms (cough, phlegm, wheeze and shortness of breath), prevalence of other related symptoms (headache and burning eyes), change in behaviour and adoption of the stove. Ethical clearance was obtained from the Institutional Ethics Committee of the Indian Institute of Public Health Hyderabad- Bengaluru Campus. Discussion The findings from this study aim to provide insight into the effects of improved cookstoves in urban slums. Results can give evidence for the decrease of indoor air pollution and the improvement of respiratory health for children and women. Trial registration The trial was registered with clinicaltrials.gov on 21 June 2016 with the identifier NCT02821650; A Study to Test the Impact of an Improved Chulha on the Respiratory Health of Women and Children in Indian Slums

Depression, Anxiety and Glucose Metabolism in the General Dutch Population: The New Hoorn Study

BACKGROUND: There is a well recognized association between depression and diabetes. However, there is little empirical data about the prevalence of depressive symptoms and anxiety among different groups of glucose metabolism in population based samples. The aim of this study was to determine whether the prevalence of increased levels of depression and anxiety is different between patients with type 2 diabetes and subjects with impaired glucose metabolism (IGM) and normal glucose metabolism (NGM). METHODOLOGY/PRINCIPAL FINDINGS: Cross-sectional data from a population-based cohort study of 2667 residents, 1261 men and 1406 women aged 40-65 years from the Hoorn region, the Netherlands. Depressive symptoms and anxiety were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D, score >or=16) and the Hospital Anxiety and Depression Scale--Anxiety Subscale (HADS-A, score >or=8), respectively. Glucose metabolism status was determined by oral glucose tolerance test. In the total study population the prevalence of depressive symptoms and anxiety for the NGM, IGM and type 2 diabetes were 12.5, 12.2 and 21.0% (P = 0.004) and 15.0, 15.3 and 19.9% (p = 0.216), respectively. In men, the prevalence of depressive symptoms was 7.7, 9.5 and 19.6% (p<0.001), and in women 16.4, 15.8 and 22.6 (p = 0.318), for participants with NGM, IGM and type 2 diabetes, respectively. Anxiety was not associated with glucose metabolism when stratified for sex. Intergroup differences (NGM vs. IGM and IGM vs. type 2 diabetes) revealed that higher prevalences of depressive symptoms are mainly manifested in participants with type 2 diabetes, and not in participants with IGM. CONCLUSIONS: Depressive symptoms, but not anxiety are associated with glucose metabolism. This association is mainly determined by a higher prevalence of depressive symptoms in participants with type 2 diabetes and not in participants with IGM

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Study protocol of effectiveness of a biopsychosocial multidisciplinary intervention in the evolution of non-speficic sub-acute low back pain in the working population : cluster randomised trial

Background: Non-specific low back pain is a common cause for consultation with the general practitioner, generating increased health and social costs. This study will analyse the effectiveness of a multidisciplinary intervention to reduce disability, severity of pain, anxiety and depression, to improve quality of life and to reduce the incidence of chronic low back pain in the working population with non-specific low back pain, compared to usual clinical care. Methods/Design: A Cluster randomised clinical trial will be conducted in 38 Primary Health Care Centres located in Barcelona, Spain and its surrounding areas. The centres are randomly allocated to the multidisciplinary intervention or to usual clinical care. Patients between 18 and 65 years old (n = 932; 466 per arm) and with a diagnostic of a non-specific sub-acute low back pain are included. Patients in the intervention group are receiving the recommendations of clinical practice guidelines, in addition to a biopsychosocial multidisciplinary intervention consisting of group educational sessions lasting a total of 10 hours. The main outcome is change in the score in the Roland Morris disability questionnaire at three months after onset of pain. Other outcomes are severity of pain, quality of life, duration of current non-specific low back pain episode, work sick leave and duration, Fear Avoidance Beliefs and Goldberg Questionnaires. Outcomes will be assessed at baseline, 3, 6 and 12 months. Analysis will be by intention to treat. The intervention effect will be assessed through the standard error of measurement and the effect-size. Responsiveness of each scale will be evaluated by standardised response mean and receiver-operating characteristic method. Recovery according to the patient will be used as an external criterion. A multilevel regression will be performed on repeated measures. The time until the current episode of low back pain takes to subside will be analysed by Cox regression. Discussion: We hope to provide evidence of the effectiveness of the proposed biopsychosocial multidisciplinary intervention in avoiding the chronification of low back pain, and to reduce the duration of non-specific low back pain episodes. If the intervention is effective, it could be applied to Primary Health Care Centres

Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopaedic surgery

Abstract. BACKGROUND: Many (artificial) bone substitute materials are currently available for use in orthopaedic trauma surgery. Objective data on their biological and biomechanical characteristics, which determine their clinical application, is mostly lacking. The aim of this study was to investigate structural and in vitro mechanical properties of nine bone substitute cements registered for use in orthopaedic trauma surgery in the Netherlands. METHODS: Seven calcium phosphate cements (BoneSource®, Calcibon®, ChronOS®, Eurobone®, HydroSet™, Norian SRS®, and Ostim®), one calcium sulphate cement (MIIG® X3), and one bioactive glass cement (Cortoss®) were tested. Structural characteristics were measured by micro-CT scanning. Compression strength and stiffness were determined following unconfined compression tests. RESULTS: Each bone substitute had unique characteristics. Mean total porosity ranged from 53% (Ostim®) to 0.5% (Norian SRS®). Mean pore size exceeded 100 μm only in Eurobone® and Cortoss® (162.2 ± 107.1 μm and 148.4 ± 70.6 μm, respectively). However, 230 μm pores were found in Calcibon®, Norian SRS®, HydroSet™, and MIIG® X3. Connectivity density ranged from 27/cm3 for HydroSet™ to 0.03/cm3 for Calcibon®. The ultimate compression strength was highest in Cortoss® (47.32 MPa) and lowest in Ostim® (0.24 MPa). Young's Modulus was highest in Calcibon® (790 MPa) and lowest in Ostim® (6 MPa). CONCLUSIONS: The bone substitutes tested display a wide range in structural properties and compression strength, indicating that they will be suitable for different clinical indications. The data outlined here will help surgeons to select the most suitable products currently available for specific clinical indications

Influence of Substrates on the Surface Characteristics and Membrane Proteome of Fibrobacter succinogenes S85

Although Fibrobacter succinogenes S85 is one of the most proficient cellulose degrading bacteria among all mesophilic organisms in the rumen of herbivores, the molecular mechanism behind cellulose degradation by this bacterium is not fully elucidated. Previous studies have indicated that cell surface proteins might play a role in adhesion to and subsequent degradation of cellulose in this bacterium. It has also been suggested that cellulose degradation machinery on the surface may be selectively expressed in response to the presence of cellulose. Based on the genome sequence, several models of cellulose degradation have been suggested. The aim of this study is to evaluate the role of the cell envelope proteins in adhesion to cellulose and to gain a better understanding of the subsequent cellulose degradation mechanism in this bacterium. Comparative analysis of the surface (exposed outer membrane) chemistry of the cells grown in glucose, acid-swollen cellulose and microcrystalline cellulose using physico-chemical characterisation techniques such as electrophoretic mobility analysis, microbial adhesion to hydrocarbons assay and Fourier transform infra-red spectroscopy, suggest that adhesion to cellulose is a consequence of an increase in protein display and a concomitant reduction in the cell surface polysaccharides in the presence of cellulose. In order to gain further understanding of the molecular mechanism of cellulose degradation in this bacterium, the cell envelope-associated proteins were enriched using affinity purification and identified by tandem mass spectrometry. In total, 185 cell envelope-associated proteins were confidently identified. Of these, 25 proteins are predicted to be involved in cellulose adhesion and degradation, and 43 proteins are involved in solute transport and energy generation. Our results supports the model that cellulose degradation in F. succinogenes occurs at the outer membrane with active transport of cellodextrins across for further metabolism of cellodextrins to glucose in the periplasmic space and inner cytoplasmic membrane

Evidence for Human Fronto-Central Gamma Activity during Long-Term Memory Encoding of Word Sequences

Although human gamma activity (30–80 Hz) associated with visual processing is often reported, it is not clear to what extend gamma activity can be reliably detected non-invasively from frontal areas during complex cognitive tasks such as long term memory (LTM) formation. We conducted a memory experiment composed of 35 blocks each having three parts: LTM encoding, working memory (WM) maintenance and LTM retrieval. In the LTM encoding and WM maintenance parts, participants had to respectively encode or maintain the order of three sequentially presented words. During LTM retrieval subjects had to reproduce these sequences. Using magnetoencephalography (MEG) we identified significant differences in the gamma and beta activity. Robust gamma activity (55–65 Hz) in left BA6 (supplementary motor area (SMA)/pre-SMA) was stronger during LTM rehearsal than during WM maintenance. The gamma activity was sustained throughout the 3.4 s rehearsal period during which a fixation cross was presented. Importantly, the difference in gamma band activity correlated with memory performance over subjects. Further we observed a weak gamma power difference in left BA6 during the first half of the LTM rehearsal interval larger for successfully than unsuccessfully reproduced word triplets. In the beta band, we found a power decrease in left anterior regions during LTM rehearsal compared to WM maintenance. Also this suppression of beta power correlated with memory performance over subjects. Our findings show that an extended network of brain areas, characterized by oscillatory activity in different frequency bands, supports the encoding of word sequences in LTM. Gamma band activity in BA6 possibly reflects memory processes associated with language and timing, and suppression of beta activity at left frontal sensors is likely to reflect the release of inhibition directly associated with the engagement of language functions