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Phenotyping occupational asthma caused by acrylates in a multicentre cohort study.
No full textBACKGROUND
While acrylates are well-known skin sensitisers, they are not classified as respiratory sensitisers although several cases of acrylate-induced occupational asthma (OA) have been reported.
OBJECTIVES
The aim of this study was to evaluate the characteristics of acrylate-induced OA in a large series of cases and compare those with OA induced by other low-molecular-weight (LMW) agents.
METHODS
Jobs and exposures, clinical and functional characteristics, and markers of airway inflammation were analysed in an international, multicentre, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge to acrylates (n= 55) or other LMW agents (n=418) including isocyanates (n=125).
RESULTS
Acrylate-containing glues were the most prevalent products and industrial manufacturing, dental work and beauty care were typical occupations causing OA. Work related rhinitis was more common in acrylate than isocyanate-induced asthma (p<0.001). The increase in post-challenge fractional exhaled nitric oxide (FeNO) was significantly greater in acrylate-induced OA (26.0, 8.2-38.0 ppb) than in OA induced by other LMW agents (3.0, -1.0-10.0 ppb, p<0.001) or isocyanates (5.0, 2.0-16.0 ppb, p=0.010). Multivariable models confirmed that OA induced by acrylates was significantly and independently associated with a post-challenge increase in FeNO (≥17.5 ppb).
CONCLUSIONS
Acrylate-induced OA shows specific characteristics, concomitant work-related rhinitis and exposure-related increases in FeNO, suggesting that acrylates may induce asthma through different immunological mechanisms than other LMW agents. Our findings reinforce the need for a re-evaluation of the hazard classification of acrylates, and further investigation of the pathophysiological mechanisms underlying their respiratory sensitizing potential
EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies.
No full textThe therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations
Standardization of Nomenclature for Ocular Tuberculosis - Results of Collaborative Ocular Tuberculosis Study (COTS) Workshop.
No full text: To standardize a nomenclature system for defining clinical phenotypes, and outcome measures for reporting clinical and research data in patients with ocular tuberculosis (OTB).: Uveitis experts initially administered and further deliberated the survey in an open meeting to determine and propose the preferred nomenclature for terms related to the OTB, terms describing the clinical phenotypes and treatment and reporting outcomes.: The group of experts reached a consensus on terming uveitis attributable to tuberculosis (TB) as tubercular uveitis. The working group introduced a SUN-compatible nomenclature that also defines disease "remission" and "cure", both of which are relevant for reporting treatment outcomes.: A consensus nomenclature system has been adopted by a large group of international uveitis experts for OTB. The working group recommends the use of standardized nomenclature to prevent ambiguity in communication and to achieve the goal of spreading awareness of this blinding uveitis entity
A national study of artificial urinary sphincter and male sling implantation following radical prostatectomy in England.
No full textOBJECTIVES
To consider the provision of post radical prostatectomy (RP) continence surgery in England.
MATERIALS AND METHODS
Patients between 01/01/2010 and 31/3/2018 with an OPCS-4 code for AUS or male sling were searched for within Hospital Episode Statistics (HES). Those without previous prostatectomy were excluded. Multivariable logistic regressions for repeat AUS and sling procedures were built in STATA. Further descriptive analysis of provision of procedures was performed.
RESULTS
1,414 patients received index AUS, 10.3% of which had prior radiotherapy; median follow-up was 3.55 years. The sling cohort contained 816 patients; 6.7% received prior radiotherapy and median follow-up was 3.23 years. Whilst the numbers of AUS implanted has increased each year, male slings peaked in 2014/2015. AUS redo/removal was performed in 11.2% patients. Patients in low volume centres were more likely to require redo/removal (OR 2.23 95%CI 1.02-4.86 p =0.045). 12.0% patients with a sling progressed to AUS and 1.3% had a second sling. Patients with previous radiotherapy were more likely to require a second operation (OR 2.03 95%CI 1.01-4.06 p=0.046). Emergency re-admissions within 30 days of index operation were 3.9% and 3.6% fewer in high volume centres, for AUS and slings respectively. Median time to initial continence surgery from RP was 2.8 years. Increased time from RP conferred no reduced risk of redo surgery for either procedure.
CONCLUSION
There is a volume effect for outcomes of AUS procedures suggesting that they should only be performed in high volume centres. Given the known impact of incontinence on quality of life, patients should be referred sooner for post-prostatectomy continence surgery
Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial.
No full textBACKGROUND
The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity.
METHODS
SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40 Gy/15F over three weeks, and 50 Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893.
FINDINGS
Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43-0.90; p = 0.012). In a planned sub-group analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26-0.88; p = 0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p < 0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p = 0.03).
INTERPRETATION
Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemo-radiation was in patients treated with anthracycline-CMF.
FUNDING
Cancer Research UK (CR UK/98/001) and Pharmacia
The Effectiveness of Pharmacological Agents for the Treatment of Uveitic Macular Edema (UMO): A Systematic Review.
No full text: To conduct a systematic review of effectiveness of pharmacological therapies for treatment of Uveitic Macular Edema (UMO). : Comparative studies of pharmacological therapies in patients with UMO were identified in Cochrane CENTRAL/MEDLINE/EMBASE/CINAHL/trials registers (February 2017). PROSPERO registration: CRD42015019170. : Thirty-one studies were included. Corticosteroids were the most frequently studied ( = 20). Corticosteroids (all forms) were consistently of greater/equal efficacy to active comparators; for anti-VEGF ( = 4) improvement, best-corrected visual acuity (BCVA) and central macular thickness (CMT) were mostly less than local corticosteroid injection; for interferon ( = 1) improvement BCVA and CMT were greater than the comparator of methotrexate; for topical indomethacin ( = 1) improvement, BCVA and CMT were greater than placebo. Non-steroidal anti-inflammatory drugs, carbonic anhydrase inhibitors, and vitamin E ( = 5) were not effective for these outcomes. : The review highlights areas where the evidence base is still lacking, and appropriately focused trials are needed to inform best treatment to tackle this sight-threatening condition
Clinicopathologic Examination of Translucent Refractile Intraluminal Tissue Coagulum From the Proximal Tube of a Baerveldt Glaucoma Drainage Device.
No full textPURPOSE
To describe an unusual case of glaucoma drainage tube blockage.
PATIENTS
A 76-year-old woman presented with left endothelial graft failure. Her previous ocular history included primary open-angle glaucoma diagnosed for 15 years and Fuch's endothelial dystrophy. Three years before presentation, the left eye required a Descemet stripping endothelial keratoplasty followed by a trabeculectomy with mitomycin C and subsequent Baerveldt tube insertion 3 years previously. Intraocular pressures were right 9 and left 19 mm Hg. The endothelial graft demonstrated supra-temporal edema, in proximity to the sulcus placed tube tip.
METHODS
A repeat endothelial keratoplasty was undertaken. During surgery, an attempt to flush the tube ab internally with balanced salt solution on a 27-G Rycroft cannula, resulted in extrusion of a long translucent tubular plug from within the silicone tube into the anterior chamber. This was removed with intraocular forceps and sent for histopathology. The endothelial keratoplasty was performed and an air bubble placed in the anterior chamber.
RESULTS
The histopathology was reported as fibrinohemorrhagic material associated with refractile material, detected under polarized light microscopy. At 6 months follow-up, the graft was clearing well, the tube in situ and the intraocular pressure 6 mm Hg.
CONCLUSIONS
One possible cause of the refractile material within the specimen is spalled particles of silicone, presumably from the tube. This finding potentially questions the long-term stability of silicone products in the eye and may be a cause of capsular fibrosis around the glaucoma drainage device plate
Healthcare transition in pediatric liver transplantation: The perspectives of pediatric and adult healthcare professionals.
No full textINTRODUCTION
Transition from pediatric to adult services of young people with a liver transplant is an important priority due to increasing numbers of young people surviving into adulthood. There is increased incidence of graft loss and non-adherence following transfer to adult services. Although studies have considered the views and perceptions of young people who have undergone liver transplantation and their parents about transition, there is currently no qualitative research with healthcare professionals working in the field of liver transplantation. The aim of this study was to elicit the views of this group of stakeholders about barriers and facilitators of an effective transition process.
METHODS
Semi-structured interviews were carried out with 11 HCPs from pediatric and adult liver transplant programs and from a range of professional backgrounds. Interviews were transcribed verbatim and analyzed using thematic analysis.
RESULTS
Four themes were identified: "non-adherence and psychosocial issues," "need for better psychological support," "the role of parents," and "the emotional impact of transition on healthcare professionals." Within these themes, professionals described factors which hindered or promoted an effective transition process.
CONCLUSIONS
Screening tools which address psychological and social aspects of the lives of young people should be used in routine practice to identify patients requiring psychosocial support and to identify those at risk of non-adherence. All staff involved with transition should be trained in the use of psychosocial screening strategies. The development of a formal referral pathway so that young people can access psychological support in adult services is recommended
Advanced endoscopic techniques in the assessment of inflammatory bowel disease: new technology, new era.
No full textEndoscopic assessment of inflammation and mucosal healing is crucial for appropriate management in IBD. Current definition of endoscopic mucosal healing has been derived using previous generation of standard white light endoscopes. New endoscopy technologies widely available provide much more detailed images of mucosal and vascular patterns. Novel endoscopic techniques with high definition image, optical and digital enhancement have enhanced the quality and fine details of vascular and mucosal pattern so that endoscopic images have started to reflect histological changes for lesions and inflammation/healing. These technologies can now define subtle inflammatory changes and increase detection and characterisation of colonic lesions in patients with IBD. The best endoscopic technique to detect dysplasia in IBD is still debated. Dye chromoendoscopy with targeted biopsies is considered by Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC consensus the standard of care and recommended for adoption by gastroenterologists in practice. In future, it is possible that well-trained colonoscopists using high definition equipment with image enhancements may be able to obtain equivalent yield without pan-colonic dye spraying and characterise lesions. Finally, SCENIC introduced endoscopic resectability of some dysplastic colonic lesions-new techniques may now better characterise endoscopic resectability and limit the number of colectomies. In this review, we will provide a state-of-the-art opinion on the direction of technological advances in the assessment of IBD and how new concepts will refine clinical practice
Violet-Blue Light Arrays at 405 Nanometers Exert Enhanced Antimicrobial Activity for Photodisinfection of Monomicrobial Nosocomial Biofilms.
No full textLight-emitting diodes (LEDs) demonstrate therapeutic effects for a range of biomedical applications, including photodisinfection. Bands of specific wavelengths (centered at 405 nm) are reported to be the most antimicrobial; however, there remains no consensus on the most effective irradiation parameters for optimal photodisinfection. The aim of this study was to assess decontamination efficiency by direct photodisinfection of monomicrobial biofilms using a violet-blue light (VBL) single-wavelength array (SWA) and multiwavelength array (MWA). Mature biofilms of nosocomial bacteria (, , , and ) were grown on 96-well polypropylene PCR plates. The biofilms were then exposed to VBL for 2,700 s (SWA) and 1,170 s (MWA) to deliver 0 to 670 J/cm, and the antibacterial activity of VBL was assessed by comparing the seeding of the irradiated and the nonirradiated biofilms. Nonirradiated groups were used as controls. The VBL arrays were characterized optically (spectral irradiance and beam profile) and thermally. The SWA delivered 401-nm VBL and the MWA delivered between 379-nm and 452-nm VBL, albeit at different irradiances and with different beam profiles. In both arrays, the irradiated groups were exposed to increased temperatures compared to the nonirradiated controls. All bacterial isolates were susceptible to VBL and demonstrated reductions in the seeding of exposed biofilms compared with the nonirradiated controls. VBL at 405 nm exerted the most antimicrobial activity, exhibiting reductions in seeding of up to 94%. Decontamination efficiency is dependent on the irradiation parameters, bacterial species and strain, and experimental conditions. Controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology. This study reports the efficacy of VBL and blue light (BL) and their antimicrobial activity against mature biofilms of a range of important nosocomial pathogens. While this study investigated the antibacterial activity of a range of wavelengths of between 375 and 450 nm and identified a specific wavelength region (∼405 nm) with increased antibacterial activity, decontamination was dependent on the bacterial species, strain, irradiation parameters, and experimental conditions. Further research with controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology