Opportunistic Infections in Rheumatoid Arthritis Patients Exposed to Biologic Therapy: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Objectives: This analysis set out to estimate the risk of opportunistic infection (OI) among patients with RA by biologic class. Methods: The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis is a prospective observational cohort study established to evaluate safety of biologic therapies. The population included adults commencing biologic therapy for RA. The primary outcome was any serious OI excluding tuberculosis (TB). Event rates were compared across biologic classes using Cox proportional hazards with adjustment for potential confounders identified a priori. Analysis of the incidence of TB was performed separately. Results: In total, 19 282 patients with 106 347 years of follow-up were studied; 142 non-TB OI were identified at a rate of 134 cases/100 000 patient years (pyrs). The overall incidence of OI was not significantly different between the different drug classes; however, the rate of Pneumocystis infection was significantly higher with rituximab than with anti-TNF therapy (adjusted hazard ratio = 3.2, 95% CI: 1.4, 7.5). The rate of TB fell dramatically over the study period (783 cases/100 000 pyrs in 2002 to 38 cases/100 000 pyrs in 2015). The incidence of TB was significantly lower among rituximab users than anti-TNF users, with 12 cases/100 000 pyrs compared with 65 cases/100 000 pyrs. Conclusions: The overall rate of OI was not significantly different between drug classes; however, a subtle difference in the pattern of OI was seen between the cohorts. Patient factors such as age, gender and comorbidity were the most important predictors of OI.info:eu-repo/semantics/publishedVersio

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Studying the Underlying Event in Drell-Yan and High Transverse Momentum Jet Production at the Tevatron

We study the underlying event in proton-antiproton collisions by examining the behavior of charged particles (transverse momentum pT > 0.5 GeV/c, pseudorapidity |\eta| < 1) produced in association with large transverse momentum jets (~2.2 fb-1) or with Drell-Yan lepton-pairs (~2.7 fb-1) in the Z-boson mass region (70 < M(pair) < 110 GeV/c2) as measured by CDF at 1.96 TeV center-of-mass energy. We use the direction of the lepton-pair (in Drell-Yan production) or the leading jet (in high-pT jet production) in each event to define three regions of \eta-\phi space; toward, away, and transverse, where \phi is the azimuthal scattering angle. For Drell-Yan production (excluding the leptons) both the toward and transverse regions are very sensitive to the underlying event. In high-pT jet production the transverse region is very sensitive to the underlying event and is separated into a MAX and MIN transverse region, which helps separate the hard component (initial and final-state radiation) from the beam-beam remnant and multiple parton interaction components of the scattering. The data are corrected to the particle level to remove detector effects and are then compared with several QCD Monte-Carlo models. The goal of this analysis is to provide data that can be used to test and improve the QCD Monte-Carlo models of the underlying event that are used to simulate hadron-hadron collisions.Comment: Submitted to Phys.Rev.

Measurement of the W+W−W^+W^- Production Cross Section and Search for Anomalous WWγWW\gamma and WWZWWZ Couplings in ppˉp \bar p Collisions at s=1.96\sqrt{s} = 1.96 TeV

This Letter describes the current most precise measurement of the $W$ boson pair production cross section and most sensitive test of anomalous $WW\gamma$ and $WWZ$ couplings in $p \bar p$ collisions at a center-of-mass energy of 1.96 TeV. The $WW$ candidates are reconstructed from decays containing two charged leptons and two neutrinos, where the charged leptons are either electrons or muons. Using data collected by the CDF II detector from 3.6 fb$^{-1}$ of integrated luminosity, a total of 654 candidate events are observed with an expected background contribution of $320 \pm 47$ events. The measured total cross section is $\sigma (p \bar p \to W^+ W^- + X) = 12.1 \pm 0.9 \textrm{(stat)} ^{+1.6}_{-1.4} \textrm{(syst)}$ pb, which is in good agreement with the standard model prediction. The same data sample is used to place constraints on anomalous $WW\gamma$ and $WWZ$ couplings.Comment: submitted to Phys. Rev. Let

Transgenic Rat Model of Neurodegeneration Caused by Mutation in the TDP Gene

TDP-43 proteinopathies have been observed in a wide range of neurodegenerative diseases. Mutations in the gene encoding TDP-43 (i.e., TDP) have been identified in amyotrophic lateral sclerosis (ALS) and in frontotemporal lobe degeneration associated with motor neuron disease. To study the consequences of TDP mutation in an intact system, we created transgenic rats expressing normal human TDP or a mutant form of human TDP with a M337V substitution. Overexpression of mutant, but not normal, TDP caused widespread neurodegeneration that predominantly affected the motor system. TDP mutation reproduced ALS phenotypes in transgenic rats, as seen by progressive degeneration of motor neurons and denervation atrophy of skeletal muscles. This robust rat model also recapitulated features of TDP-43 proteinopathies including the formation of TDP-43 inclusions, cytoplasmic localization of phosphorylated TDP-43, and fragmentation of TDP-43 protein. TDP transgenic rats will be useful for deciphering the mechanisms underlying TDP-43–related neurodegenerative diseases

Workplace violence in a large correctional health servce in New South Wales, Australia: a retrospective review of incident management records

BackgroundLittle is known about workplace violence among correctional health professionals. This studyaimed to describe the patterns, severity and outcomes of incidents of workplace violenceamong employees of a large correctional health service, and to explore the help-seekingbehaviours of staff following an incident.MethodsThe study setting was Justice Health, a statutory health corporation established to providehealth care to people who come into contact with the criminal justice system in New SouthWales, Australia. We reviewed incident management records describing workplace violenceamong Justice Health staff. The three-year study period was 1/7/2007-30/6/2010.ResultsDuring the period under review, 208 incidents of workplace violence were recorded. Verbalabuse (71%) was more common than physical abuse (29%). The most (44%) incidents ofworkplace violence (including both verbal and physical abuse) occurred in adult maleprisons, although the most (50%) incidents of physical abuse occurred in a forensic hospital.Most (90%) of the victims were nurses and two-thirds were females. Younger employees andmales were most likely to be a victim of physical abuse. Preparing or dispensing medicationand attempting to calm and/or restrain an aggressive patient were identified as ‘high risk’work duties for verbal abuse and physical abuse, respectively. Most (93%) of the incidents ofworkplace violence were initiated by a prisoner/patient. Almost all of the incidents receivedeither a medium (46%) or low (52%) Severity Assessment Code. Few victims of workplaceviolence incurred a serious physical injury – there were no workplace deaths during the studyperiod. However, mental stress was common, especially among the victims of verbal abuse(85%). Few (6%) victims of verbal abuse sought help from a health professional.ConclusionsAmong employees of a large correctional health service, verbal abuse in the workplace wassubstantially more common than physical abuse. The most incidents of workplace violenceoccurred in adult male prisons. Review of the types of adverse health outcomes experiencedby the victims of workplace violence and the assessments of severity assigned to violentincidents suggests that, compared with health care settings in the community, correctionalsettings are fairly safe places in which to practice

Character pathology and neuropsychological test performance in remitted opiate dependence

<p>Abstract</p> <p>Background</p> <p>Cognitive deficits and personality pathology are prevalent in opiate dependence, even during periods of remission, and likely contribute to relapse. Understanding the relationship between the two in vulnerable, opiate-addicted patients may contribute to the design of better treatment and relapse prevention strategies.</p> <p>Methods</p> <p>The Millon Multiaxial Clinical Inventory (MCMI) and a series of neuropsychological tests were administered to three subject groups: 29 subjects receiving methadone maintenance treatment (MM), 27 subjects in protracted abstinence from methadone maintenance treatment (PA), and 29 healthy non-dependent comparison subjects. Relationships between MCMI scores, neuropsychological test results, and measures of substance use and treatment were examined using bivariate correlation and regression analysis.</p> <p>Results</p> <p>MCMI scores were greater in subjects with a history of opiate dependence than in comparison subjects. A significant negative correlation between MCMI scores and neuropsychological test performance was identified in all subjects. MCMI scores were stronger predictors of neuropsychological test performance than measures of drug use.</p> <p>Conclusion</p> <p>Formerly methadone-treated opiate dependent individuals in protracted opiate abstinence demonstrate a strong relationship between personality pathology and cognitive deficits. The cause of these deficits is unclear and most likely multi-factorial. This finding may be important in understanding and interpreting neuropsychological testing deficiencies in opiate-dependent subjects.</p

Characterizing the role of rice NRAMP5 in Manganese, Iron and Cadmium Transport

Metals like manganese (Mn) and iron (Fe) are essential for metabolism, while cadmium (Cd) is toxic for virtually all living organisms. Understanding the transport of these metals is important for breeding better crops. We have identified that OsNRAMP5 contributes to Mn, Fe and Cd transport in rice. OsNRAMP5 expression was restricted to roots epidermis, exodermis, and outer layers of the cortex as well as in tissues around the xylem. OsNRAMP5 localized to the plasma membrane, and complemented the growth of yeast strains defective in Mn, Fe, and Cd transport. OsNRAMP5 RNAi (OsNRAMP5i) plants accumulated less Mn in the roots, and less Mn and Fe in shoots, and xylem sap. The suppression of OsNRAMP5 promoted Cd translocation to shoots, highlighting the importance of this gene for Cd phytoremediation. These data reveal that OsNRAMP5 contributes to Mn, Cd, and Fe transport in rice and is important for plant growth and development