Evaluation of measurement properties of self-administered PROMs aimed at patients with non-specific shoulder pain and "activity limitations": a systematic review.

To critically appraise and compare the measurement properties of self-administered patient-reported outcome measures (PROMs) focussing on the shoulder, assessing "activity limitations."Systematic review. The study population had to consist of patients with shoulder pain. We excluded postoperative patients or patients with generic diseases. The methodological quality of the selected studies and the results of the measurement properties were critically appraised and rated using the COSMIN checklist.Out of a total of 3427 unique hits, 31 articles, evaluating 7 different questionnaires, were included. The SPADI is the most frequently evaluated PROM and its measurement properties seem adequate apart from a lack of information regarding its measurement error and content validity.For English, Norwegian and Turkish users, we recommend to use the SPADI. Dutch users could use either the SDQ or the SST. In German, we recommend the DASH. In Tamil, Slovene, Spanish and the Danish languages, the evaluated PROMs were not yet of acceptable validity. None of these PROMs showed strong positive evidence for all measurement properties. We propose to develop a new shoulder PROM focused on activity limitations, taking new knowledge and techniques into account

Discontinuation of a randomised controlled trial in general practice due to unsuccessful patient recruitment.

BACKGROUND: A randomised controlled trial (RCT) in general practice, recruiting incident patients with (sub)acute sciatica, was discontinued because of insufficient recruitment. AIM: To describe factors that influenced the recruitment process and ultimately led to discontinuation of this trial, and to enable others to learn from this experience. DESIGN & SETTING: A pragmatic RCT was designed to compare two pain medication prescription strategies for treatment of (sub)acute sciatica in general practice. After 1 year of patient recruitment, the trial was prematurely terminated. METHOD: To analyse the underperforming recruitment, patient information systems of 20 general practices were screened twice a month to search for eligible patients and identify reasons for non-eligibility. Secondly, after study termination, an open question was distributed to the participating GPs for their views on the recruitment process. RESULTS: A total of 116 GPs from 37 general practices collaborated in the trial. Only eight of 234 patients were included after 12 months. The 22 GPs who offered their opinion on the main reasons for unsuccessful recruitment considered that these were the low incidence rate and strict eligibility criteria, a strong patient and/or GP preference, and time constraints. CONCLUSION: For this RCT, multiple factors were related to recruitment problems but it remains unknown which determinants prevailed. As the research question is unanswered but remains relevant, it is recommended that GPs' daily practice is taken into account when designing an RCT, a pilot study should be performed for feasibility of recruitment, and GP assistants should be involved at an early stage

Methanotrophic potential of Dutch canal wall biofilms is driven by Methylomonadaceae

Global urbanization of waterways over the past millennium has influenced microbial communities in these aquatic ecosystems. Increased nutrient inputs have turned most urban waters into net sources of the greenhouse gases carbon dioxide (CO2) and methane (CH4). Here, canal walls of five Dutch cities were studied for their biofilm CH4 oxidation potential, alongside field observations of water chemistry, and CO2 and CH4 emissions. Three cities showed canal wall biofilms with relatively high biological CH4 oxidation potential up to 0.48 mmol gDW-1 d-1, whereas the other two cities showed no oxidation potential. Salinity was identified as the main driver of biofilm bacterial community composition. Crenothrix and Methyloglobulus methanotrophs were observed in CH4-oxidizing biofilms. We show that microbial oxidation in canal biofilms is widespread and is likely driven by the same taxa found across cities with distinctly different canal water chemistry. The oxidation potential of the biofilms was not correlated with the amount of CH4 emitted but was related to the presence or absence of methanotrophs in the biofilms. This was controlled by whether there was enough CH4 present to sustain a methanotrophic community. These results demonstrate that canal wall biofilms can directly contribute to the mitigation of greenhouse gases from urban canals

Regulation of caspase-3 processing by cIAP2 controls the switch between pro-inflammatory activation and cell death in microglia.

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material.The activation of microglia, resident immune cells of the central nervous system, and inflammation-mediated neurotoxicity are typical features of neurodegenerative diseases, for example, Alzheimer's and Parkinson's diseases. An unexpected role of caspase-3, commonly known to have executioner role for apoptosis, was uncovered in the microglia activation process. A central question emerging from this finding is what prevents caspase-3 during the microglia activation from killing those cells? Caspase-3 activation occurs as a two-step process, where the zymogen is first cleaved by upstream caspases, such as caspase-8, to form intermediate, yet still active, p19/p12 complex; thereafter, autocatalytic processing generates the fully mature p17/p12 form of the enzyme. Here, we show that the induction of cellular inhibitor of apoptosis protein 2 (cIAP2) expression upon microglia activation prevents the conversion of caspase-3 p19 subunit to p17 subunit and is responsible for restraining caspase-3 in terms of activity and subcellular localization. We demonstrate that counteracting the repressive effect of cIAP2 on caspase-3 activation, using small interfering RNA targeting cIAP2 or a SMAC mimetic such as the BV6 compound, reduced the pro-inflammatory activation of microglia cells and promoted their death. We propose that the different caspase-3 functions in microglia, and potentially other cell types, reside in the active caspase-3 complexes formed. These results also could indicate cIAP2 as a possible therapeutic target to modulate microglia pro-inflammatory activation and associated neurotoxicity observed in neurodegenerative disorders

Comparison between 2000 and 2018 on the reporting of statistical significance and clinical relevance in physiotherapy clinical trials in six major physiotherapy journals: a meta-research design

DesignMeta-research.ObjectiveTo compare the prevalence of reporting p values, effect estimates and clinical relevance in physiotherapy randomised controlled trials (RCTs) published in the years 2000 and 2018.MethodsWe performed a meta-research study of physiotherapy RCTs obtained from six major physiotherapy peer-reviewed journals that were published in the years 2000 and 2018. We searched the databases Embase, Medline and PubMed in May 2019, and extracted data on the study characteristics and whether articles reported on statistical significance, effect estimates and confidence intervals for baseline, between-group, and within-group differences, and clinical relevance. Data were presented using descriptive statistics and inferences were made based on proportions. A 20% difference between 2000 and 2018 was regarded as a meaningful difference.ResultsWe found 140 RCTs: 39 were published in 2000 and 101 in 2018. Overall, there was a high prevalence (>90%) of reporting p values for the main (between-group) analysis, with no difference between years. Statistical significance testing was frequently used for evaluating baseline differences, increasing from 28% in 2000 to 61.4% in 2018. The prevalence of reporting effect estimates, CIs and the mention of clinical relevance increased from 2000 to 2018 by 26.6%, 34% and 32.8% respectively. Despite an increase in use in 2018, over 40% of RCTs failed to report effect estimates, CIs and clinical relevance of results.ConclusionThe prevalence of using p values remains high in physiotherapy research. Although the proportion of reporting effect estimates, CIs and clinical relevance is higher in 2018 compared to 2000, many publications still fail to report and interpret study findings in this way.</jats:sec

Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas

Dysregulation of apoptosis plays an important role in tumour progression and resistance to chemotherapy. The X-linked inhibitor of apoptosis ( XIAP) is considered to be the most potent caspase inhibitor of all known inhibitor of apoptosis-family members. Only recently, an antagonist of XIAP has been identified, termed Smac/DIABLO. To explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs), we analysed XIAP and Smac/DIABLO mRNA and protein expression in the primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA. X-linked inhibitor of apoptosis and Smac/DIABLO mRNA expression was found in all RCCs. Importantly, the relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages ( P = 0.0002) and also with tumour dedifferentiation ( P = 0.04). Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. Consequently, the mRNA expression ratio between antiapoptotic XIAP and proapoptotic Smac/DIABLO markedly increased during progression from early ( pT1) to advanced ( pT3) tumour stages. Moreover, RCCs confined within the organ capsule ( pT1 and pT2) exhibited a significantly lower XIAP to Smac/DIABLO expression ratio when compared with RCCs infiltrating beyond the kidney ( pT3; P = 0.01). Thus, our investigation demonstrates that the delicate balance between XIAP and Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of antiapoptotic XIAP over proapoptotic Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.OncologySCI(E)46ARTICLE71349-13579

The effect of Tai Chi Chuan in reducing falls among elderly people: design of a randomized clinical trial in the Netherlands [ISRCTN98840266]

BACKGROUND: Falls are a significant public health problem. Thirty to fifty percent of the elderly of 65 years and older fall each year. Falls are the most common type of accident in this age group and can result in fractures and subsequent disabilities, increased fear of falling, social isolation, decreased mobility, and even an increased mortality. Several forms of exercise have been associated with a reduced risk of falling and with a wide range of physiological as well as psychosocial health benefits. Tai Chi Chuan seems to be the most promising form of exercise in the elderly, but the evidence is still controversial. In this article the design of a randomized clinical trial is presented. The trial evaluates the effect of Tai Chi Chuan on fall prevention and physical and psychological function in older adults. METHODS/DESIGN: 270 people of seventy years and older living at home will be identified in the files of the participating general practitioners. People will be asked to participate when meeting the following inclusion criteria: have experienced a fall in the preceding year or suffer from two of the following risk factors: disturbed balance, mobility problems, dizziness, or the use of benzodiazepines or diuretics. People will be randomly allocated to either the Tai Chi Chuan group (13 weeks, twice a week) or the no treatment control group. The primary outcome measure is the number of new falls, measured with a diary. The secondary outcome measures are balance, fear of falling, blood pressure, heart rate, lung function parameters, physical activity, functional status, quality of life, mental health, use of walking devices, medication, use of health care services, adjustments to the house, severity of fall incidents and subsequent injuries. Process parameters will be measured to evaluate the Tai Chi Chuan intervention. A cost-effectiveness analysis will be carried out alongside the evaluation of the clinical results. Follow-up measurements will be collected at 3, 6 and 12 months after randomization. DISCUSSION: As far as we know this is the first trial in Europe considering Tai Chi Chuan and fall prevention. This project will answer a pragmatic research question regarding the efficacy of Tai Chi Chuan regarding fall reduction

Influenza A virus evolution and spatio-temporal dynamics in Eurasian wild birds: a phylogenetic and phylogeographical study of whole-genome sequence data.

Low pathogenic avian influenza A viruses (IAVs) have a natural host reservoir in wild waterbirds and the potential to spread to other host species. Here, we investigated the evolutionary, spatial and temporal dynamics of avian IAVs in Eurasian wild birds. We used whole-genome sequences collected as part of an intensive long-term Eurasian wild bird surveillance study, and combined this genetic data with temporal and spatial information to explore the virus evolutionary dynamics. Frequent reassortment and co-circulating lineages were observed for all eight genomic RNA segments over time. There was no apparent species-specific effect on the diversity of the avian IAVs. There was a spatial and temporal relationship between the Eurasian sequences and significant viral migration of avian IAVs from West Eurasia towards Central Eurasia. The observed viral migration patterns differed between segments. Furthermore, we discuss the challenges faced when analysing these surveillance and sequence data, and the caveats to be borne in mind when drawing conclusions from the apparent results of such analyses.We thank all ornithologists and other collaborators for their continuous support. We thank V. Munster, E. Skepner, O. Vuong, C. Baas, J. Guldemeester, M. Schutten, G. van der Water, D. Smith and E. Bortz for technical support and stimulating discussions. This manuscript was prepared while D.E. Wentworth was employed at the JCVI. The opinions expressed in this article are the author’s own and do not reflect the view of the Centers for Disease Control, the Department of Health and Human Services, or the United States government. This work was supported by NIAID/NIH contract HHSN266200700010C, HHSN272201400008C, HHSN272201400006C and HHSN272200900007C, a Wellcome Trust Fellowship Strategic Travel Award under contract WT089235MF, a DTRA FRCWMD Broad Agency Announcement under contract HDTRA1-09-14-FRCWMD GRANT11177182, by the EU Framework six program NewFluBird (044490) by contracts with the Dutch Ministry of Economic Affairs and a NIAID/NIH CEIRS travel grant under contract HHSN266200700010C. The Swedish sampling and analysis was supported by the Swedish Research Councils VR and FORMAS.This is the final version of the article. It first appeared from the Society for General Microbiology via http://dx.doi.org/10.1099/vir.0.00015

A soccer player with idiopathic osteonecrosis of the complete lateral talar dome: a case report

We report a 13-year-old soccer player with osteonecrosis of the talus and a large carticular fragment. The defect was revitalized with curettage and drilling and filled with autologous bone graft followed by the fixation of the carticular fragment with two conventional lag screws. Screw placement was such that they could be removed arthroscopically. Healing was uneventful. Eighteen months postoperative hardware was indeed removed arthroscopically. He returned to his former competitive level without restrictions or complaints

Modification of the FoxP3 Transcription Factor Principally Affects Inducible T Regulatory Cells in a Model of Experimental Autoimmune Encephalomyelitis

T regulatory (Treg) cells expressing the transcription factor FoxP3 play a key role in protection against autoimmune disease. GFP-FoxP3 reporter mice have been used widely to study the induction, function and stability of both thymically- and peripherally-induced Treg cells. The N-terminal modification of FoxP3, however, affects its interaction with transcriptional co-factors; this can alter Treg cell development and function in certain self-antigen specific animal models. Interestingly, Treg cell function can be negatively or positively affected, depending on the nature of the model. In this study, we focused on the effect of the GFP-FoxP3 reporter on Treg cell development and function in the Tg4 mouse model. In this model, T cells express a transgenic T cell receptor (TCR) specific for the Myelin Basic Protein (MBP) peptide Ac1-9, making the animals susceptible to experimental autoimmune encephalomyelitis (EAE), a disease akin to multiple sclerosis in humans. Unlike diabetes-susceptible mice, Tg4 FoxP3(gfp) mice did not develop spontaneous autoimmune disease and did not demonstrate augmented susceptibility to induced disease. Concurrently, thymic generation of natural Treg cells was not negatively affected. The induction of FoxP3 expression in naive peripheral T cells was, however, significantly impaired as a result of the transgene. This study shows that the requirements for the interaction of FoxP3 with co-factors, which governs its regulatory ability, differ not only between natural and inducible Treg cells but also between animal models of diseases such as diabetes and EAE