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Improved performance predicting clarithromycin resistance in Mycobacterium abscessus on an independent dataset.
No full textIn our recent study of 203 sequential isolates evaluating the ability of whole genome sequencing (WGS) to predict clarithromycin resistance in () (1), we demonstrated high sensitivity but poor specificity of mutations identified in a literature search. …
IM-UNITI: 3 Year Efficacy, Safety, and Immunogenicity of Ustekinumab Treatment of Crohn's Disease.
No full textBACKGROUND AND AIMS
Following induction/maintenance treatment in the UNITI/IM-UNITI studies of ustekinumab for Crohn's disease, patients entered a long-term extension for up to 5 years from induction. Efficacy through 152 and safety through 156 weeks are reported.
METHODS
At IM-UNITI Week 44, 567 ustekinumab-treated patients entered the long-term extension and continued to receive blinded subcutaneous ustekinumab on their assigned dose interval, without any subsequent dose adjustment. Placebo-treated patients discontinued after study unblinding (after IM-UNITI Week 44 analyses). Efficacy data in the LTE were collected every 12 weeks (q12w) prior to unblinding and then at q12w/q8w dosing visits.
RESULTS
Through Week 156, 29.6% of ustekinumab-treated patients discontinued. In an intent-to-treat analysis of randomized patients from IM-UNITI Week 0-152, 38.0% of ustekinumab induction responders receiving drug q12w and 43.0% q8w were in remission at Week 152. Among patients entering the long-term extension in their original randomized groups, 61.9% of q12w and 69.5% of q8w patients were in remission at Week 152. Across all ustekinumab-treated patients (randomized and non-randomized) entering the long-term extension, remission rates at Week 152 were 56.3% and 55.1% for q12w and q8w, respectively.
CONCLUSION
Continued treatment with subcutaneous ustekinumab maintained clinical response and remission through 3 years in a majority of patients who responded to induction therapy and was well-tolerated. ClinicalTrials.gov number NCT01369355
Severe atherosclerosis of donor hepatic arteries is a salvageable condition in liver transplantation to optimise the graft utilisation: A case series and review of the literature.
No full textINTRODUCTION
The presence of atherosclerosis of the common hepatic artery (CHA) in donor livers potentially contributes to vascular complications after liver transplantation, thereby most of those organs are traditionally discarded. Herein, we describe the successful outcome of three patients transplanted with grafts that had severe atherosclerosis of the donor CHA up to the level of the gastroduodenal artery (GDA).
PRESENTATION OF CASE
In all three cases, endarterectomies were performed by dissection between the atheromatous core and the artery intima using a dissecting spatula, allowing to secure the lumen of the vessel. The native CHA/GDA patch was aligned with the corresponding CHA/GDA patch from the graft for the arterial reconstruction. No vascular complications were seen post-operatively.
DISCUSSION
Endarterectomy and anatomical reconstitution of the arterial tree, without any redundancy or kinking, allowed for the successful transplantation of organs that would be otherwise discarded. Further, the straight alignment of the arteries may enhance flow dynamics, preventing thrombosis.
CONCLUSION
This report might guide future studies targeting means to increase the utility of donor livers discarded due to arterial atherosclerosis
Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology.
No full textResident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases
Interventions to Increase the Rate of Influenza and Pneumococcal Vaccination in Patients with Chronic Obstructive Pulmonary Disease: A Scoping Review.
No full textCurrent evidence suggests that patients with chronic obstructive pulmonary disease (COPD) should receive influenza and pneumococcal vaccinations. Despite international guidelines recommending vaccination in patients with COPD, many patients remain unvaccinated. Reasons for vaccine non-acceptance are multifaceted and are likely to be influenced by multiple psychosocial factors and pre-existing health beliefs. The aim of this review was to identify interventions which have been shown to effectively increase vaccination rates in patients with COPD. A structured search of PubMed returned 491 titles. Following title and abstract screening, seven full-text articles reporting on 6 unique interventional studies were extracted for narrative synthesis. A variety of interventions were investigated which, for the purposes of this review, were grouped into patient-focussed, clinician-focussed and mixed interventions. Three papers reported findings from clinical trials (2 unique studies) and 4 papers reported findings from before-after studies. Two studies were conducted in the primary care setting, the remaining studies were conducted in secondary and tertiary care. Most studies reported both influenza and pneumococcal vaccination rates. These studies suggest that multimodal interventions, which target multiple aspects of evidence-based care and use both patient-focussed and clinician-focussed techniques, may have the greatest impact on vaccination rates in patients with COPD. Further, adequately powered, high quality studies are needed. It is crucial for individual institutions to monitor their own vaccination rates to determine if there is scope for performance improvement
2018 Update of the EULAR recommendations for the management of large vessel vasculitis.
No full textBACKGROUND
Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.
METHODS
Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.
RESULTS
Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.
CONCLUSIONS
We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice
Occupational asthma; the limited role of air-fed respiratory protective equipment.
No full textBACKGROUND
Evidence-based reviews have found that evidence for the efficacy of respiratory protective equipment (RPE) in the management of occupational asthma (OA) is lacking.
AIMS
To quantify the effectiveness of air-fed RPE in workers with sensitizer-induced OA exposed to metal-working fluid aerosols in a car engine and transmission manufacturing facility.
METHODS
All workers from an outbreak of metal-working fluid-induced OA who had continuing peak expiratory flow (PEF) evidence of sensitizer-induced OA after steam cleaning and replacement of all metal-working fluid were included. Workers kept 2-hourly PEF measurements at home and work, before and after a strictly enforced programme of RPE with air-fed respirators with charcoal filters. The area-between-curve (ABC) score from the Oasys plotter was used to assess the effectiveness of the RPE.
RESULTS
Twenty workers met the inclusion criteria. Records were kept for a mean of 24.6 day shifts and rest days before and 24.7 after the institution of RPE. The ABC score improved from 26.6 (SD 16.2) to 17.7 (SD 25.4) l/min/h (P > 0.05) post-RPE; however, work-related decline was <15 l/min/h in only 12 of 20 workers, despite increased asthma treatment in 5 workers.
CONCLUSIONS
Serial PEF measurements assessed with the ABC score from the Oasys system allowed quantification of the effect of RPE in sensitized workers. The RPE reduced falls in PEF associated with work exposure, but this was rarely complete. This study suggests that RPE use cannot be relied on to replace source control in workers with OA, and that monitoring post-RPE introduction is needed
Phenotypic characteristics and risk factors in a multi-ethnic cohort of young adults with type 2 diabetes.
No full textEarly onset of type 2 diabetes (T2DM) is associated with prolonged exposure to hyperglycaemia and increased propensity to chronic complications. The aim of this study was to characterise and compare the phenotypic characteristics and risk factors in a multi-ethnic cohort of young adults with type 2 diabetes (T2DMY). 100 young adults (White European [WE], South Asian [SA] and African-Caribbean [AC]) diagnosed with T2DM before the age of 40 years were recruited. Demographics, family history, diabetes related complications, co-morbidities, anthropometry (Body Mass Index (BMI), Body composition), physical activity and biochemistry (HbA1c, lipid profile, liver and renal function) and autoantibodies (anti GAD, anti islet cell) were collected for all participants. Data were analysed for the most represented ethnic groups: (WE, N = 36 and SA, N = 53) using SPSS version 23. Mean (± standard deviation) age at diagnosis was 32.5 ± 5.5 years and mean diabetes duration was 7.7 ± 3.8 years. Overweight/obesity was present in 95% of participants, history of maternal diabetes in 68%, deprivation 75%, low physical activity 40%, polycystic ovarian disease 29% (in females), acanthosis nigricans 12%, and non alcoholic fatty liver 11%. There was considerable clustering of risk factors within the cohort with over 75% of all subjects having 3 or more of the above risk factors and fifty two percent required insulin within 3 years of diagnosis. Two-thirds of the patients had evidence of at least one diabetes related micro-vascular complication. T2DMY is characterised by a high burden of commonly associated risk factors for both the disease and its long-term complications
Developing a Process for Criteria-Led Discharge: Selection of Patients for Efficient and Effective Discharge (SPEED).
No full textBACKGROUND
Criteria-led discharge (CLD) is an approach for maximizing bed capacity by expediting patient discharge.
PROBLEM
In acute medicine settings, patients commonly have multiple medical problems, which render single care pathway and clinical protocols of limited use. CLD offers potential, but little evidence exists about how to best implement it in these contexts.
APPROACH
Retrospective case note analysis generated characteristics from patients' discharge plans to design a criterion-based framework to aid patient selection for CLD. These criteria were hypothetically tested on patient case notes (n = 50).
OUTCOMES
CLD was identified as suitable (n = 27) and unsuitable (n = 23) from 50 case notes. Interrater agreement was 86% between 3 reviewers.
CONCLUSIONS
This review has provided greater understanding of the complexity of discharge in acute medicine settings. Implementing CLD to optimize timeliness of patient discharge might offer a solution for selected patients