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Relapse rates after elective discontinuation of anti-TNF therapy in rheumatoid arthritis: a meta-analysis and review of literature
Full text link© The Author(s) 2019
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.Abstract
Background
Inhibitors of tumor necrosis factor alpha (TNF-α) are current mainstay of therapies for rheumatoid arthritis (RA). The decision when to withdraw TNF-α inhibitors after achieving remission and the incidence of relapse rates with elective discontinuation are both important questions that demand intense survey in these patients. In this meta-analysis we aimed to estimate the magnitude of relapse rate after elective TNF-α inhibitor discontinuation in RA patients with remission.
Methods
Systematic searches of PubMed/MEDLINE, Cochrane Library databases, grey literature (unpublished and ongoing trials) from the WHO International Clinical Trials Registry Platform and the US National Institutes of Health were performed for studies reporting the outcomes of elective discontinuation of TNF-α inhibitor in RA patients after remission. Random-effects models for meta-analyses were conducted on extracted data.
Results
Out of 390 references screened, 16 RCTs were included. Meta-analysis of 1264 patient data revealed a relapse rate of 0.47 (95% CI 0.41–0.54). Sensitivity analysis showed that none of the studies had higher influence on the results.
Conclusions
Almost half of all the RA patients in remission relapse after elective TNF-α inhibitor discontinuation. This information might be useful when considering this management option with individual patients
Electrically Sorted Single-Walled Carbon Nanotubes-Based Electron Transporting Layers for Perovskite Solar Cells
Full text link© 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Incorporation of as prepared single-walled carbon nanotubes (SWCNTs) into the electron transporting layer (ETL) is an effective strategy to enhance the photovoltaic performance of perovskite solar cells (PSCs). However, the fundamental role of the SWCNT electrical types in the PSCs is not well understood. Herein, we prepared semiconducting (s-) and metallic (m-) SWCNT families and integrated them into TiO2 photoelectrodes of the PSCs. Based on experimental and theoretical studies, we found that the electrical type of the nanotubes plays an important role in the devices. In particular, the mixture of s-SWCNTs and m-SWCNTs (2:1 w/w)-based PSCs exhibited a remarkable efficiency of up to 19.35%, which was significantly higher than that of the best control cell (17.04%). In this class of PSCs, semiconducting properties of s-SWCNTs play a critical role in extracting and transporting electrons, whereas m-SWCNTs provide high conductance throughout the electrode
Sudden natural death behind the wheel: Review of driver deaths and fitness to drive assessment history in Victoria, Australia 2012–2013
Full text link© 2018 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (February 2019) in accordance with the publisher’s archiving policyThis study reviews the circumstances and medical causes of death of motor vehicle drivers who died in circumstances of sudden illness whilst behind the wheel in Victoria, Australia 2012-13. The driver's fitness to drive assessment history was also examined to identify prevention opportunities.
Deaths included in the study were those referred to a panel responsible for determining whether the driver fatality should be included in the official road toll, where prior doubt exists. A research team comprising of forensic physicians examined the case file of each death involving sudden illness.
Forty-five driver deaths during the two-year period were reviewed. Ischaemic heart disease was the most common cause of death. Over 80% of drivers were male with a median age of 64 years. While limited medical history was available, significantly impacting study analysis, findings identified minimal opportunity to improve the fitness to drive review process
Creating the first national linked dataset on perinatal and maternal outcomes in Australia: Methods and challenges
Full text link© 2019 Elsevier Inc. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:
http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (March 2019) in accordance with the publisher’s archiving policyBackground
Data linkage offers a powerful mechanism for examining healthcare outcomes across populations and can generate substantial robust datasets using routinely collected electronic data. However, it presents methodological challenges, especially in Australia where eight separate states and territories maintain health datasets. This study used linked data to investigate perinatal and maternal outcomes in relation to place of birth. It examined data from all eight jurisdictions regarding births planned in hospitals, birth centres and at home. Data linkage enabled the first Australia-wide dataset on birth outcomes. However, jurisdictional differences in data collection created challenges in obtaining comparable cohorts of women with similar low-risk pregnancies in all birth settings. The objective of this paper is to describe the techniques for managing previously linked data, and specifically for ensuring the resulting dataset contained only low-risk pregnancies.
Methods
This paper indicates the procedures for preparing and merging linked perinatal, inpatient and mortality data from different sources, providing technical guidance to address challenges arising in linked data study designs.
Results
We combined data from eight jurisdictions linking four collections of administrative healthcare and civil registration data. The merging process ensured that variables were consistent, compatible and relevant to study aims. To generate comparable cohorts for all three birth settings, we developed increasingly complex strategies to ensure that the dataset eliminated women with pregnancies at risk of complications during labour and birth. It was then possible to compare birth outcomes for comparable samples, enabling specific examination of the impact of birth setting on maternal and infant safety across Australia.
Conclusions
Data linkage is a valuable resource to enhance knowledge about birth outcomes from different settings, notwithstanding methodological challenges. Researchers can develop and share practical techniques to address these challenges. Study findings suggest that jurisdictions develop more consistent data collections to facilitate future data linkage
Using audit and feedback to increase clinician adherence to clinical practice guidelines in brain injury rehabilitation: A before and after study
Full text linkCopyright: © 2019 Jolliffe et al. This 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.Objective
This study evaluated whether frequent (fortnightly) audit and feedback cycles over a sustained period of time (>12 months) increased clinician adherence to recommended guidelines in acquired brain injury rehabilitation.
Design
A before and after study design.
Setting
A metropolitan inpatient brain injury rehabilitation unit.
Participants
Clinicians; medical, nursing and allied health staff.
Interventions
Fortnightly cycles of audit and feedback for 14 months. Each fortnight, medical file and observational audits were completed against 114 clinical indicators.
Main outcome measure
Adherence to guideline indicators before and after intervention, calculated by proportions, Mann-Whitney U and Chi square analysis.
Results
Clinical and statistical significant improvements in median clinical indicator adherence were found immediately following the audit and feedback program from 38.8% (95% CI 34.3 to 44.4) to 83.6% (95% CI 81.8 to 88.5). Three months after cessation of the intervention, median adherence had decreased from 82.3% to 76.6% (95% CI 72.7 to 83.3, p<0.01). Findings suggest that there are individual indicators which are more amenable to change using an audit and feedback program.
Conclusion
A fortnightly audit and feedback program increased clinicians’ adherence to guideline recommendations in an inpatient acquired brain injury rehabilitation setting. We propose future studies build on the evidence-based method used in the present study to determine effectiveness and develop an implementation toolkit for scale-up
A realist review of infant feeding counselling to increase exclusive breastfeeding by HIV-positive women in sub Saharan-Africa: what works for whom and in what contexts
Full text link© The Author(s). 2019 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.The most recent World Health Organization (WHO) guidelines on Human Immunodeficiency Virus (HIV) and infant feeding promotes exclusive breastfeeding (EBF) in resource limited settings for the prevention of mother to child transmission (PMTCT) of HIV. Literature reveals poor uptake of WHO feeding guidelines, with mixed feeding being a regular practice. In light of the limited success in EBF promotion, a realist review was conducted, analysing the use of feeding counselling to increase exclusive breastfeeding by HIV-positive women in sub Saharan-Africa, where the majority of HIV childhood infections occur. We considered what mechanisms were at play, for whom and in what circumstances they led to exclusive breastfeeding
Strategic Groundwater Research Partnership Final Report
No full textCopyright: This work is copyright. Apart from any use permitted under the Copyright Act 1968, no part may be reproduced by any process, nor may any other exclusive rights be exercised, without the permission of Flinders University, GPO Box 2100, Adelaide 5001, South Australia, 2018.The MDBA-NCGRT Strategic Groundwater Research Partnership was a three year, $2 million research program funded by the Murray-Darling Basin Authority between 2015 and 2018. Its overarching goal was to undertake strategic research in support of enhanced groundwater knowledge and management in the Murray-Darling Basin (MDB). It has examined critical science issues in three thematic priority areas, namely:
• SW-GW Connectivity: improving knowledge and predictive capacity at the regional scale in the MDB;
• Groundwater Recharge: increasing our understanding of MDB recharge processes with a strong emphasis on improving recharge estimation and predictions techniques, and quantifying and managing uncertainty in recharge estimation;
• Socioeconomics and Integration: identifying the socioeconomic factors that will improve water management in the MDB, including factors such as conjunctive use; building tools and approaches in a participatory relationship that facilitates the integration of important biophysical and social models, knowledge and data.
Research on these issues was advanced through a range of modelling and field-based projects. A focus case study was chosen to be in the Campaspe in north-central Victoria. Some activities were also undertaken in the Murrumbidgee catchment. Many of the approaches and findings presented in this report, and associated papers and reports, are based on work in the Campaspe region. We anticipate that many of the approaches developed here will be applicable in and transferable to many parts of the Murray-Darling Basin. However, they should be evaluated and tested on a case by case basis to ensure applicability and transferability.
The Partnership has considerably enhanced the MDBA and NCGRT’s scientific and socioeconomic knowledge base; delivered state-of-the-art modelling processes and integrated assessment tools for managing groundwater in the Basin with a particular focus on understanding and managing surface water and groundwater interaction in the future; leveraged the NCGRT’s extensive national and international network of groundwater scientists and field research sites and equipment; trained postgraduate students to build relevant capacity for the future; delivered innovative new scientific and management tools and practises to support integrated catchment scale socio-hydrology; and produced transferable outcomes that will assist in the management of major Basin groundwater systems in the MDB. The approaches and findings from this Partnership will allow government and industry to better understand, conceptualise, measure, model, predict and manage groundwater behaviour in the Basin – both biophysically and socially. These underpin important policy and management frameworks and state / national strategic planning for water, environmental and agricultural security in the Basin.
The Murray-Darling Basin Authority – NCGRT Strategic Groundwater Research Partnership has led to a number of key findings that form the basis for key recommendations in each of the above priority areas, as well as for groundwater modelling and groundwater management. These key findings and recommendations given are presented in this report. They are not prioritised or presented in any order of importance
Intraocular Chemotherapy for Vitreoretinal Lymphoma: a review
Full text link© 2019 Royal Australian and New Zealand College of OphthalmologistsVitreoretinal lymphomas are rare ocular cancers, and the subset of primary central nervous system lymphomas that are based in the posterior eye. These tumours are challenging to treat, and today management generally involves a multispecialty team coordinating a treatment protocol that may include intraocular chemotherapy, ocular irradiation, systemic chemotherapy and/or autologous stem cell transplantation. The ophthalmologist has specific responsibility for the intraocular chemotherapy, which is delivered to the eye by intravitreal injection. The most commonly injected drugs are methotrexate—an anti‐metabolite—and rituximab—an anti‐human B cell monoclonal antibody. A range of intraocular chemotherapy treatment schedules have been described in the medical literature, although to date there have been no randomized clinical trials of these schedules. In this article, we review the development and current status of intraocular chemotherapy for vitreoretinal lymphoma
Diverse dynamics features of novel protein kinase C (PKC) isozymes determine the selectivity of a fluorinated balanol analogue for PKCε
Full text linkThis 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.Abstract
Background
(−)-Balanol is an ATP-mimicking inhibitor that non-selectively targets protein kinase C (PKC) isozymes and cAMP-dependent protein kinase (PKA). While PKA constantly shows tumor promoting activities, PKC isozymes can ambiguously be tumor promoters or suppressors. In particular, PKCε is frequently implicated in tumorigenesis and a potential target for anticancer drugs. We recently reported that the C5(S)-fluorinated balanol analogue (balanoid 1c) had improved binding affinity and selectivity for PKCε but not to the other novel PKC isozymes, which share a highly similar ATP site. The underlying basis for this fluorine-based selectivity is not entirely comprehended and needs to be investigated further for the development of ATP mimic inhibitors specific for PKCε.
Results
Using molecular dynamics (MD) simulations assisted by homology modelling and sequence analysis, we have studied the fluorine-based selectivity in the highly similar ATP sites of novel PKC (nPKC) isozymes. The study suggests that every nPKC isozyme has different dynamics behaviour in both apo and 1c-bound forms. Interestingly, the apo form of PKCε, where 1c binds strongly, shows the highest degree of flexibility which dramatically decreases after binding 1c.
Conclusions
For the first time to the best of our knowledge, we found that the origin of 1c selectivity for PKCε comes from the unique dynamics feature of each PKC isozyme. Fluorine conformational control in 1c can synergize with and lock down the dynamics of PKCε, which optimize binding interactions with the ATP site residues of the enzyme, particularly the invariant Lys437. This finding has implications for further rational design of balanol-based PKCε inhibitors for cancer drug development
Long term prognostic importance of late gadolinium enhancement in first-presentation non-ischaemic dilated cardiomyopathy
Full text link© 2019 Elsevier B.V. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (January 2019) in accordance with the publisher’s archiving policyBackground
Presence of myocardial fibrosis in well-established non-ischaemic dilated cardiomyopathy (NIDCM) is associated with adverse clinical outcomes. However, the impact of myocardial fibrosis at first presentation in NIDCM, and its long-term association with left ventricular (LV) dysfunction, heart failure (HF) and ventricular arrhythmia (VA) remains unclear. We investigated whether the presence of myocardial fibrosis quantified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) at presentation, is independently associated with long-term major adverse cardiovascular events (MACE) in patients with first presentation NIDCM.
Methods
Consecutive patients with a first diagnosis of NIDCM were recruited. Patients underwent LGE-CMR at baseline. Replacement myocardial fibrosis by LGE-CMR was quantified by experienced observers blinded to patient outcome. MACE was defined as a composite end-point including cardiac death, HF rehospitalisation and the occurrence of sustained VA.
Results
Fifty-one patients with first presentation NIDCM were included, of which 49 (96%) had follow up and outcome data. Median follow up was 8.2 years. Both the LGE positive and LGE negative groups had similar clinical characteristics at follow up. In univariate Cox regression analysis, positive LGE was associated with MACE (HR:3.44; 95% CI:1.89 to 6.24, p-value < 0.001) and HF rehospitalisation (HR:2.89; 95% CI:1.42 to 5.85, p-value = 0.003). In multivariate Cox regression, positive LGE-CMR was independently associated with MACE (HR:3.53; 95% CI:1.51 to 8.27, p-value = 0.004) and HF rehospitalisation (HR:3.07; 95% CI:1.24 to 7.59, p-value = 0.015).
Conclusions
The presence of myocardial fibrosis in first presentation NIDCM is independently associated with an increased risk of HF rehospitalisation, at long term follow-up