Persons with chronic widespread pain experience excess mortality : longitudinal results from UK Biobank and meta-analysis

This manuscript uses the UK Biobank resource (Application 1144). We acknowledge the authors of a previous meta-analysis on this topic (Diane Smith, Ross Wilkie, Olalekan Uthman, Joanne L. Jordan, John McBeth) whose published search strategy we used as the basis for our meta-analysis, albeit that our meta-analysis had a more restricted focus and the criteria for determining eligibility and the data we extracted from eligible studies was not identical and resulted in selection of a different group of studies. We thank John McBeth (University of Manchester) for providing additional data relating to one of the studies, to allow it be included in the meta-analysis. GJM had the idea for the study and together with GTJ designed the analysis plan for UK Biobank. GTJ undertook the UK Biobank analysis. MSB conducted the updated systematic review and all authors participated in undertaking the meta-analysis. GJM drafted the manuscript but all authors made an important intellectual contribution to the text. None of the authors report conflict of interest.Peer reviewedPostprin

The effects of surface structure mutations in <i>Arabidopsis thaliana</i> on the polarization of reflections from virus-infected leaves

<div><p>The way in which light is polarized when reflected from leaves can be affected by infection with plant viruses. This has the potential to influence viral transmission by insect vectors due to altered visual attractiveness of infected plants. The optical and topological properties of cuticular waxes and trichomes are important determinants of how light is polarized upon reflection. Changes in expression of genes involved in the formation of surface structures have also been reported following viral infection. This paper investigates the role of altered surface structures in virus-induced changes to polarization reflection from leaves. The percentage polarization of reflections from <i>Arabidopsis thaliana cer5</i>, <i>cer6</i> and <i>cer8</i> wax synthesis mutants, and the <i>gl1</i> leaf hair mutant, was compared to those from wild-type (WT) leaves. The <i>cer5</i> mutant leaves were less polarizing than WT on the adaxial and abaxial surfaces; <i>gl1</i> leaves were more polarizing than WT on the adaxial surfaces. The <i>cer6</i> and <i>cer8</i> mutations did not significantly affect polarization reflection. The impacts of <i>Turnip vein clearing virus</i> (TVCV) infection on the polarization of reflected light were significantly affected by <i>cer5</i> mutation, with the reflections from <i>cer5</i> mutants being higher than those from WT leaves, suggesting that changes in <i>CER5</i> expression following infection could influence the polarization of the reflections. There was, however, no significant effect of the <i>gl1</i> mutation on polarization following TVCV infection. The <i>cer5</i> and <i>gl1</i> mutations did not affect the changes in polarization following <i>Cucumber mosaic virus</i> (CMV) infection. The accumulation of TVCV and CMV did not differ significantly between mutant and WT leaves, suggesting that altered expression of surface structure genes does not significantly affect viral titres, raising the possibility that if such regulatory changes have any adaptive value it may possibly be through impacts on viral transmission.</p></div

Co-Occurrence and Characteristics of Patients With Axial Spondyloarthritis Who Meet Criteria for Fibromyalgia : Results From a UK National Register

The British Society for Rheumatology (BSR) Biologics Register in Ankylosing Spondylitis is funded by the BSR and they have receive funds for this from Pfizer, AbbVie and UCB. These companies receive advance copies of manuscripts and can provide comments but have no input into determining the topics for analysis, publication and no input into the work involved in this analysis. This analysis is part-funded by Arthritis Research UK (Grant No: 21378)Peer reviewedPublisher PD

Prescribing competency assessment for Canadian medical students: a pilot evaluation

Background: The knowledge and ability to prescribe safely and effectively is a core competency for every graduating medical student. Our previous research suggested concerns about medical student prescribing abilities, and interest in a standardized assessment process. Methods: A multi-year cross-sectional study evaluating the feasibility, acceptability, and discriminative ability of an online prescribing competency assessment for final year Canadian medical students was conducted. Students at nine sites of four Ontario medical schools were invited to participate in an online one-hour exam of eight domains related to prescribing safely. Student feedback on perceived fairness, clarity, and ease of use formed the primary outcome. Exam performance and parity between schools were the secondary outcome.  Results: A total of 714 students completed the assessment during spring final review courses between 2016 and 2018. Student feedback was more favourable than not for appropriateness of content (53.5% agreement vs 18.3% disagreement), clarity of questions (65.5% agreement vs 11.6% disagreement), question layout and presentation (70.8% agreement vs 12.2% disagreement), and ease of use of online interface (67.1% agreement vs 13.6% disagreement). Few (23.6% believed their course work had prepared them for the assessment. Mean total exam score was 70.0% overall (SD 10.4%), with 47.6% scoring at or above the pass threshold of 70%. Conclusion: Our prescribing competency assessment proved feasible, acceptable, and discriminative, and indicated a need for better medical school training to improve prescribing competency. Further evaluation in a larger sample of medical schools is warranted

Management Outcomes in Splenic Injury: A Statewide Trauma Center Review

OBJECTIVE: Clinical pathways now highlight both observation and operation as acceptable initial therapeutic options for the management of patients with splenic injury. The purpose of this study was to evaluate treatment trends for splenic injury in all North Carolina trauma centers over a 6-year period. METHODS: Splenic injuries in adults over a 6-year period (January 1988-December 1993) were identified in the North Carolina Trauma Registry using ICD-9-CM codes. Patients were divided into four groups by method of management: 1) no spleen operation, 2) splenectomy, 3) definitive splenorrhaphy, and 4) splenorrhaphy failure followed by splenectomy. The authors examined age, mechanism of injury, admitting blood pressure, and severity of injury by trauma score and injury severity score. SUMMARY BACKGROUND DATA: Comparisons were made between adult (17-64 years of age) and geriatric (older than 65 years of age) patients and between patients with blunt and penetrating injury. Resource utilization (length of stay, hospital charges) and outcome (mortality) were compared. RESULTS: One thousand two hundred fifty-five patients were identified with splenic injury. Rate of splenic preservation increased over time and was achieved in more than 50% of patients through nonoperative management (40%) and splenorrhaphy (12%). Splenorrhaphy was not used commonly in either blunt or penetrating injury. Overall mortality was 13%. Geriatric patients had a higher mortality and resource utilization regardless of their mechanism of injury or method of management. CONCLUSIONS: Nonoperative management represents the prevailing method of splenic preservation in both the adult and geriatric population in North Carolina trauma center hospitals. Satisfactory outcomes and economic advantages accompany nonoperative management in this adult population

The British Society for Rheumatology Biologics Registers in Ankylosing Spondylitis (BSRBR-AS) study : Protocol for a prospective cohort study of the long-term safety and quality of life outcomes of biologic treatment

Acknowledgements Oversight of the study is provided by the BSR Registers Committee of which GJM and GTJ are members, together with investigators from BSRBR-RA, representatives from the BSR clinical affairs section and BSR independent members, currently, Alex MacGregor (University of East Anglia), Elaine Dennison (University of Southampton), Jon Packham (Keele University) and patient representatives Ailsa Bosworth and Debbie Cook. We acknowledge the contribution of the International Advisory Group members Desireé van der Heijde (Netherlands), Matthew Brown (Australia) and Walter Maksymowych (Canada). We thank Neil Basu (University of Aberdeen) for his role with regards to pharmacovigilance and the Robertson Centre for Biostatistics (University of Glasgow) for data management services. Author KTM is currently at the Tayside Clinical Trials Unit, University of Dundee. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Peer reviewedPublisher PD

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis

Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 μg mL–1, P =.223; 3.6 vs 3.5 μg mL–1, P =.569; 50.1 vs 46.8 μg mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival

Physical and mental health comorbidity is common in people with multiple sclerosis: nationally representative cross-sectional population database analysis

&lt;b&gt;Background&lt;/b&gt; Comorbidity in Multiple Sclerosis (MS) is associated with worse health and higher mortality. This study aims to describe clinician recorded comorbidities in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; 39 comorbidities in 3826 people with MS aged ≥25 years were compared against 1,268,859 controls. Results were analysed by age, gender, and socioeconomic status, with unadjusted and adjusted Odds Ratios (ORs) calculated using logistic regression. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; People with MS were more likely to have one (OR 2.44; 95% CI 2.26-2.64), two (OR 1.49; 95% CI 1.38-1.62), three (OR 1.86; 95% CI 1.69-2.04), four or more (OR 1.61; 95% CI 1.47-1.77) non-MS chronic conditions than controls, and greater mental health comorbidity (OR 2.94; 95% CI 2.75-3.14), which increased as the number of physical comorbidities rose. Cardiovascular conditions, including atrial fibrillation (OR 0.49; 95% CI 0.36-0.67), chronic kidney disease (OR 0.51; 95% CI 0.40-0.65), heart failure (OR 0.62; 95% CI 0.45-0.85), coronary heart disease (OR 0.64; 95% CI 0.52-0.71), and hypertension (OR 0.65; 95% CI 0.59-0.72) were significantly less common in people with MS. &lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; People with MS have excess multiple chronic conditions, with associated increased mental health comorbidity. The low recorded cardiovascular comorbidity warrants further investigation

Computational simulation of Haidinger's brushes

Haidinger's brushes (HB) are entoptic phenomena resulting from differential absorption of linear polarized light by the human macula. Computational models have assisted in understanding the behavior of these subjective phenomena but have been limited in their application. This study presents a revised computational model that incorporates known determinants of the form and behavior of HB. The model generates both static and animated simulations of HB that can be quantified by their density, contrast, and radial/circumferential extent. Measured physiological parameters are used to demonstrate the dependency of HB on macular pigment (MP) density, MP distribution, and ocular retardation. Physiological variations in these parameters explain the reported variations in the perception of HB