Publications by authors named "Ruth Murphy"

47 Publications

Behçet's syndrome in children and young people in the United Kingdom & Republic of Ireland: a prospective epidemiological study.

Rheumatology (Oxford) 2021 Feb 2. Epub 2021 Feb 2.

Department of Rheumatology, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.

Objectives: To define the incidence and prevalence of Behçet's syndrome (BS) in children and young people (CYP) up to the age of 16 years in the United Kingdom (UK) and Republic of Ireland (ROI).

Methods: A prospective epidemiological study was undertaken with the support of the British Paediatric Surveillance Unit (BPSU) and the British Society of Paediatric Dermatologists (BSPD). Consultants reported anonymised cases of BS seen. A follow-up study at one year examined progression of disease and treatment.

Results: Over a two-year period, 56 cases met International Criteria for Behçet's Disease. For children under 16 years of age, the two-year period prevalence estimate was 4.2 per million (95% CI 3.2-5.4) and the incidence was 0.96 per million person years (95% CI 0.66-1.41). Mucocutaneous disease was the most common phenotype (56/100%), with ocular (10/56; 17.9%), neurological (2/56; 3.6%) and vascular involvement (3/56; 5.4%) being less common. Median age at onset was 6.34 years and at diagnosis was 11.72 years. There were slightly more female than male children reported (32/56; 55.6%). The majority of cases (85.7%) were white Caucasian. Apart from genital ulcers, which were more common in females, there were no significant differences in frequency of manifestations between male or females, nor between ethnicities. Over 83% of cases had three or more non-primary care healthcare professionals involved in their care.

Conclusion: BS is extremely rare in CYP in the UK and ROI and most have mucocutaneous disease. Healthcare needs are complex, and coordinated care is key.
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http://dx.doi.org/10.1093/rheumatology/keab084DOI Listing
February 2021

Plasma cell mucositis related to qat chewing: a report of 2 cases and review of the literature.

Oral Surg Oral Med Oral Pathol Oral Radiol 2021 Mar 30;131(3):e65-e70. Epub 2020 Sep 30.

Oral Medicine, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, England.

Plasma cell mucositis is a rare, benign mucosal condition with characteristic histological features of a dense polyclonal plasmacytic infiltrate. A variety of mucosal sites are affected and the presentation varies from a cobblestone to an intensely erythematous, lobulated appearance. Idiopathic cases are well documented and it has been attempted to define the entity as a hypersensitivity reaction, however reports show inconsistencies. The last two decades have highlighted an emerging association between qat (khat) chewing and plasma cell mucositis. This report provides a review of the most pertinent literature and describes two cases intimately related to qat chewing, whereby resolution occurred upon qat cessation. One case requiring systemic steroidal therapy due to severe symptoms. This highlights the need for an increased awareness amongst clinicians of a potential aetiological link between qat and plasma cell mucositis, emphasises the benefit of qat cessation and the scenarios whereby systemic steroidal therapy should be considered.
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http://dx.doi.org/10.1016/j.oooo.2020.09.009DOI Listing
March 2021

Interventions for treating oral lichen planus: corticosteroid therapies.

Cochrane Database Syst Rev 2020 02 28;2:CD001168. Epub 2020 Feb 28.

University of Newcastle upon Tyne, Department of Oral Medicine, School of Dental Sciences, Framlington Place, Newcastle upon Tyne, UK, NE2 4BW.

Background: Oral lichen planus (OLP) is a relatively common chronic T cell-mediated disease, which can cause significant pain, particularly in its erosive or ulcerative forms. As pain is the indication for treatment of OLP, pain resolution is the primary outcome for this review. This review is an update of a version last published in 2011, but focuses on the evidence for corticosteroid treatment only. A second review considering non-corticosteroid treatments is in progress.

Objectives: To assess the effects and safety of corticosteroids, in any formulation, for treating people with symptoms of oral lichen planus.

Search Methods: Cochrane Oral Health's Information Specialist searched the following databases to 25 February 2019: Cochrane Oral Health's Trials Register, CENTRAL (2019, Issue 1), MEDLINE Ovid, and Embase Ovid. ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. There were no restrictions on language or date of publication.

Selection Criteria: We considered randomised controlled clinical trials (RCTs) of any local or systemic corticosteroid treatment compared with a placebo, a calcineurin inhibitor, another corticosteroid, any other local or systemic (or both) drug, or the same corticosteroid plus an adjunctive treatment.

Data Collection And Analysis: Three review authors independently scanned the titles and abstracts of all reports identified, and assessed risk of bias using the Cochrane tool and extracted data from included studies. For dichotomous outcomes, we expressed the estimates of effects of an intervention as risk ratios (RR), with 95% confidence intervals (CI). For continuous outcomes, we used mean differences (MD) and 95% CI. The statistical unit of analysis was the participant. We conducted meta-analyses only with studies of similar comparisons reporting the same outcome measures. We assessed the overall certainty of the evidence using GRADE.

Main Results: We included 35 studies (1474 participants) in this review. We assessed seven studies at low risk of bias overall, 11 at unclear and the remaining 17 studies at high risk of bias. We present results for our main outcomes, pain and clinical resolution measured at the end of the treatment course (between one week and six months), and adverse effects. The limited evidence available for comparisons between different corticosteroids, and corticosteroids versus alternative or adjunctive treatments is presented in the full review. Corticosteroids versus placebo Three studies evaluated the effectiveness and safety of topical corticosteroids in an adhesive base compared to placebo. We were able to combine two studies in meta-analyses, one evaluating clobetasol propionate and the other flucinonide. We found low-certainty evidence that pain may be more likely to be resolved when using a topical corticosteroid rather than a placebo (RR 1.91, 95% CI 1.08 to 3.36; 2 studies, 72 participants; I² = 0%). The results for clinical effect of treatment and adverse effects were inconclusive (clinical resolution: RR 6.00, 95% CI 0.76 to 47.58; 2 studies, 72 participants; I² = 0%; very low-certainty evidence; adverse effects RR 1.48, 95% 0.48 to 4.56; 3 studies, 88 participants, I² = 0%, very low-certainty evidence). Corticosteroids versus calcineurin inhibitors Three studies compared topical clobetasol propionate versus topical tacrolimus. We found very low-certainty evidence regarding any difference between tacrolimus and clobetasol for the outcomes pain resolution (RR 0.45, 95% CI 0.24 to 0.88; 2 studies, 100 participants; I² = 80%), clinical resolution (RR 0.61, 95% CI 0.38 to 0.99; 2 studies, 52 participants; I² = 95%) and adverse effects (RR 0.05, 95% CI 0.00 to 0.83; 2 studies, 100 participants; very low-certainty evidence) . One study (39 participants) compared topical clobetasol and ciclosporin, and provided only very low-certainty evidence regarding the rate of clinical resolution with clobetasol (RR 3.16, 95% CI 1.00 to 9.93), pain resolution (RR 2.11, 95% CI 0.76 to 5.86) and adverse effects (RR 6.32, 95% CI 0.84 to 47.69). Two studies (60 participants) that compared triamcinolone and tacrolimus found uncertain evidence regarding the rate of clinical resolution (RR 0.86, 95% CI 0.55 to 1.35; very low-certainty evidence) and that there may be a lower rate of adverse effects in the triamcinolone group (RR 0.47, 95% CI 0.22 to 0.99; low-certainty evidence). These studies did not report on pain resolution.

Authors' Conclusions: Corticosteroids have been first line for the treatment of OLP. This review found that these drugs, delivered topically as adhesive gels or similar preparations, may be more effective than placebo for reducing the pain of symptomatic OLP; however, with the small number of studies and participants, our confidence in the reliability of this finding is low. The results for clinical response were inconclusive, and we are uncertain about adverse effects. Very low-certainty evidence suggests that calcineurin inhibitors, specifically tacrolimus, may be more effective at resolving pain than corticosteroids, although there is some uncertainty about adverse effects and clinical response to tacrolimus showed conflicting results.
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http://dx.doi.org/10.1002/14651858.CD001168.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047223PMC
February 2020

A Comparison of Psoriasis Severity in Pediatric Patients Treated With Methotrexate vs Biologic Agents.

JAMA Dermatol 2020 04;156(4):384-392

Department of Dermatology, Radboud University, Nijmegen, the Netherlands.

Importance: Few studies have compared the use of methotrexate and biologics, the most commonly used systemic medications for treatment of moderate to severe psoriasis in children.

Objective: To assess the real-world, 6-month reduction in psoriasis severity and long-term drug survival (rate and duration of adherence to a specific drug) of methotrexate vs biologics in plaque psoriasis in children.

Design, Setting, And Participants: A retrospective medical records review was conducted at 20 European and North American centers. Treatment response was based on site-reported Psoriasis Area and Severity Index (PASI) and/or Physician Global Assessment (PGA) scores at baseline and within the first 6 months of treatment. Participants included all 234 consecutively seen children with moderate to severe psoriasis who received at least 3 months of methotrexate or biologics from December 1, 1990, to September 16, 2014, with sufficient data for analysis. Data analysis was performed from December 14, 2015, to September 1, 2016.

Main Outcomes And Measures: PASI, with a range from 0 to 72 (highest score indicating severe psoriasis), and/or PGA, with a scale of 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), and 5 (very severe).

Results: Of 234 pediatric patients (103 boys [44.0%]; 131 girls [56.0%]) treated with methotrexate and/or biologics, 163 patients (69.7%) exclusively received methotrexate, 47 patients (20.1%) exclusively received biologics, and 24 children (10.2%) received methotrexate and biologics sequentially. Of the latter cohort, 23 children were treated initially with methotrexate. Mean (SD) age at initiation was 11.6 (3.7) years for methotrexate and 13.3 (2.9) years for biologics (73.2% for etanercept) (P = .002). Among patients evaluated by a scoring method at 6-month follow-up, 75% or greater improvement in PASI (PASI75) was achieved in 12 of 30 patients (40.0%) receiving methotrexate and 20 of 28 patients (71.4%) receiving biologics, and PGA was clear/almost clear (PGA 0/1) in 41 of 115 patients (35.6%) receiving methotrexate and 18 of 37 patients (48.6%) receiving biologics. Achieving PASI75 and/or PGA 0/1 between baseline and 6 months was more likely with biologics than methotrexate (PASI75: odds ratio [OR], 4.56; 95% CI, 2.02-10.27; P < .001; and PGA 0/1: OR, 2.00; 95% CI, 0.98-4.00; P = .06). Decreased mean PASI and PGA scores were associated with biologics more than with methotrexate (PASI effect, -3.13; 95% CI, -4.33 to -1.94; P < .001; and PGA effect, -0.31; 95% CI, -0.56 to -0.06; P = .02). After 1, 3, and 5 years of use, overall drug survival rates for methotrexate were 77.5%, 50.3%, and 35.9%, and for biologics, the rates were 83.4%, 64.3%, and 57.1%, respectively. Biologics were associated with a better confounder-corrected drug survival than methotrexate (hazard ratio [HR], 2.23; 95% CI, 1.21-4.10; P = .01). Discontinuation owing to lack of response was comparable (HR, 1.64; 95% CI, 0.80-3.36; P = .18).

Conclusions And Relevance: Methotrexate and biologics appear to be associated with improvement in pediatric psoriasis, although biologics seem to be associated with greater reduction in psoriasis severity scores and higher drug survival rates than methotrexate in the real-world setting. Additional studies directly comparing these medications should be performed for confirmation.
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http://dx.doi.org/10.1001/jamadermatol.2019.4835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042803PMC
April 2020

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Clin Transl Sci 2020 03 29;13(2):400-409. Epub 2020 Jan 29.

St. John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (E ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes.
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http://dx.doi.org/10.1111/cts.12725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070790PMC
March 2020

Age, psychiatry admission status and linear mental capacity for treatment decisions.

Int J Law Psychiatry 2019 Sep - Oct;66:101469. Epub 2019 Jul 17.

Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin D24 NR0A, Ireland. Electronic address:

The relationship between age and mental capacity among psychiatry inpatients is not fully understood. We aimed to assess mental capacity for treatment decisions in voluntary and involuntary psychiatry inpatients in Ireland and, in this analysis of our data-set, to elucidate the linear relationship, if any, between linear (as opposed to categorical) mental capacity and age. We used the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) to assess mental capacity for treatment decisions in 215 psychiatry inpatients (176 voluntary and 39 involuntary) in four psychiatry admission units in Ireland. Mean age was 46.2 years and majorities were male (58.1%), never married (74.0%), unemployed (64.2%) and of Irish ethnicity (87.0%). The most common primary diagnoses were schizophrenia and related disorders (42.8%) followed by affective disorders (36.7%). On multi-variable linear regression analysis, linear mental capacity was significantly associated with voluntary admission status, being employed, having a primary diagnosis other than schizophrenia or a related disorder, and younger age. Together, these factors accounted for 44.4% of the variance in mental capacity between participants. Overall, while increased age is associated with diminished mental capacity, other factors appear more significant, including involuntary admission status which is likely an indicator of symptom severity. There is a need for further research to (a) elucidate the relationships between the significant factors identified in this study and the cognitive status of patients (which impacts on assessments of mental capacity); (b) identify and elucidate other factors of likely relevance to mental capacity (e.g. medical illness, medication use); and (c) translate these findings into targeted interventions to support decision-making in clinical practice among psychiatry inpatients, especially those with involuntary status.
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http://dx.doi.org/10.1016/j.ijlp.2019.101469DOI Listing
May 2020

Convergence or Divergence? Comparing Mental Capacity Assessments Based on Legal and Clinical Criteria in Medical and Surgical Inpatients.

J Leg Med 2019 Jul-Sep;39(3):213-227

Despite the high prevalence of mental incapacity for treatment decisions in hospitals (27.7%), there is little information about the relationship, if any, between mental capacity assessments based on clinical and legal criteria. We performed a cross-sectional study of mental incapacity for treatment decisions in 300 hospital inpatients in two hospitals in Ireland, using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and the legal definition of mental incapacity in Ireland's incoming Assisted Decision-Making (Capacity) Act 2015. We found that patients who lacked mental capacity according to the legal criteria scored significantly lower on all four subscales of the MacCAT-T (Understanding, Appreciation, Reasoning, and Communication) compared to those who had mental capacity according to the legal criteria. In light of the similarity between Ireland's legal definition of mental incapacity and legislative definitions in other jurisdictions (e.g. England and Wales), we conclude that legal assessments of mental incapacity in these countries accord closely with clinical assessments (as reflected in the MacCAT-T). Ireland's new mental capacity legislation should be implemented promptly in order to further operationalize Ireland's new legal definition of mental incapacity and provide patients with the supports they need to optimize their mental capacity for treatment decisions in hospitals.
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http://dx.doi.org/10.1080/01947648.2019.1622476DOI Listing
December 2019

Association of Serum Ustekinumab Levels With Clinical Response in Psoriasis.

JAMA Dermatol 2019 Sep 18. Epub 2019 Sep 18.

St John's Institute of Dermatology, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.

Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab.

Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis.

Design, Setting, And Participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria.

Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay.

Main Outcomes And Measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less.

Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5).

Conclusions And Relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.
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http://dx.doi.org/10.1001/jamadermatol.2019.1783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751771PMC
September 2019

Do we need a core curriculum for medical students? A scoping review.

BMJ Open 2019 08 30;9(8):e027369. Epub 2019 Aug 30.

Medical Education Centre, School of Medicine, University of Nottingham, Nottingham, UK.

Objective: The General Medical Council (GMC) recommends medical schools to develop and implement curricula enabling students to achieve the required learning outcomes. UK medical schools follow the GMC's Outcomes for graduates, which are generic. GMC plans to introduce a national Medical Licensing Assessment (MLA) for the medical graduates wanting to practise medicine in the UK in 2022. With no standardised or unified undergraduate (UG) curriculum in UK, various specialties have expressed concerns about not being represented in medical schools and developed specialty-specific core curricula. The aim of this review was to identify learned bodies who have developed a core curriculum for UK medical schools and highlight the drivers, gaps and future approaches to curricular development and implementation.

Methods: A literature search was conducted using online databases (EMBASE, MEDLINE, ERIC, HMIC, PubMed and CDSR), search engines and related websites (Google and Google Scholar, Department of Health, GMC and BMA) for relevant articles from 1996 to 5 March 2019 (~20 years). A methodological framework to map the key concepts of UG medical curriculum was followed. Any relevant body with a core curriculum for UK medical UGs was included.

Results: A total of 1283 articles were analysed with 31 articles included in the qualitative synthesis, comprising 26 specialties (clinical n=18, foundation subjects n=4 and professionalism related n=4). WHO, European and national (eg, Royal Colleges of UK) specialty bodies provided specific core learning outcomes for the medical graduates. Patient safety, disease burden, needs of society and inadequate preparedness of medical graduates were drivers for the development of these curricula.

Conclusions: This is the first comprehensive review of literature on UG core curricula recommending minimum standards on knowledge and skills, in alignment with GMC's Outcomes for graduates for all the UK medical students. Adopting and assessing unified standards would help reduce variability across UK medical schools for both generic and specialty-specific competencies.
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http://dx.doi.org/10.1136/bmjopen-2018-027369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720253PMC
August 2019

Protocol for a case-control diagnostic accuracy study to develop diagnostic criteria for psoriasis in children (DIPSOC study): a multicentre study recruiting in UK paediatric dermatology clinics.

BMJ Open 2019 08 27;9(8):e028689. Epub 2019 Aug 27.

Centre of Evidence Based Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.

Introduction: Diagnosing psoriasis in children can be challenging. Early and accurate diagnosis is important to ensure patients receive psoriasis specific treatment and monitoring. It is recognised that the physical, psychological, quality of life, financial and comorbid burden of psoriasis are significant. The aim of this study is to develop clinical examination and history-based diagnostic criteria for psoriasis in children to help differentiate psoriasis from other scaly inflammatory rashes. The criteria tested in this study were developed through a consensus study with a group of international psoriasis experts (International Psoriasis Council).

Methods And Analysis: Children and young people (<18 years) with psoriasis (cases) and other scaly inflammatory skin diseases (controls) diagnosed by a dermatologist are eligible for recruitment. All participants complete a single research visit including a diagnostic criteria assessment by a trained investigator blinded to the participant's diagnosis. The reference standard of a dermatologist's diagnosis is extracted from the medical record. Sensitivity and specificity of the consensus derived diagnostic criteria will be calculated and the best predictive criteria developed using multivariate logistic regression.

Ethics And Dissemination: Health Regulatory Authority and National Health Service Research Ethics Committee approvals were granted in February 2017 (REC Ref: 17/EM/0035). Dissemination will be guided by stakeholders; patients, children and young people, dermatologists, primary care and paediatric rheumatologists. The aim is to publish the study results in a high-quality peer-reviewed journal, present the findings at international academic meetings and disseminate more widely through social media and working with patient associations.

Trial Registration Number: ISRCTN98851260.
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http://dx.doi.org/10.1136/bmjopen-2018-028689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720549PMC
August 2019

Categorical mental capacity for treatment decisions among psychiatry inpatients in Ireland.

Int J Law Psychiatry 2019 May - Jun;64:53-59. Epub 2019 Feb 6.

Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin 24 D24 NR0A, Ireland. Electronic address:

This study aimed to assess mental capacity for treatment decisions among psychiatry inpatients in Ireland and explore the relationship, if any, between mental capacity and various demographics and clinical variables. We assessed mental capacity for treatment decisions in 215 psychiatry inpatients in four psychiatry admission units. Almost half of the participants were female and the most common diagnoses were schizophrenia or a related disorder and affective disorders. Overall, 1.9% of participants lacked mental capacity for treatment decisions; 50.7% had partial mental capacity; and 47.4% had full mental capacity. These proportions did not differ between female and male patients. On multi-variable regression analysis, greater mental capacity was significantly associated with, in order of strength of association, voluntary admission status, Irish ethnicity, being employed and younger age. However, while these relationships were statistically significant (i.e. were unlikely to have occurred by chance), together they accounted for just 27.6% of the variance in mental capacity between participants (i.e. they were not very strong). The relatively high rate of "partial mental capacity" identified in our work suggests that decision-making supports are likely to be of substantial importance in assisting psychiatry inpatients making decisions about treatment, especially involuntary inpatients whose mental capacity is especially likely to be impaired. Future research could usefully clarify and quantify the role of cognitive and other factors in relation to the unexplained variance (72.4%) in mental capacity identified in this study; and explore which models of supported decision-making are most likely to assist the substantial proportion (50.7%) of psychiatry inpatients who have partial mental capacity for treatment decisions, as well as the minority lacking such mental capacity (1.9%).
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http://dx.doi.org/10.1016/j.ijlp.2019.02.001DOI Listing
February 2020

Concordance of mental capacity assessments based on legal and clinical criteria: A cross-sectional study of psychiatry inpatients.

Psychiatry Res 2019 06 9;276:160-166. Epub 2019 May 9.

Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin 24, D24 NR0A, Ireland. Electronic address:

This study aimed to compare assessments of mental capacity based on legal criteria with assessments based on clinical criteria among psychiatry inpatients to establish the concordance, if any, between these two approaches to assessing mental capacity. We assessed mental capacity for treatment decisions in 215 psychiatry inpatients (176 voluntary and 39 involuntary) in four psychiatry admission units in Ireland using both legal criteria (Ireland's Assisted Decision-Making (Capacity) Act 2015) and clinical criteria (the MacArthur Competence Assessment Tool for Treatment; MacCAT-T). Over one third of participants (34.9%) lacked mental capacity for treatment decisions according to the legal criteria. Mental incapacity was associated with involuntary admission status, being unemployed, a primary diagnosis of schizophrenia or a related disorder, and older age. Patients who lacked mental capacity according to the legislation scored significantly lower on all subscales of the MacCAT-T than patients who had mental capacity. We conclude that mental capacity assessments based on legal criteria correlate closely with those based on clinical criteria. These findings support current legal definitions of mental incapacity in Ireland and other jurisdictions with similar legislation (e.g. England and Wales).
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http://dx.doi.org/10.1016/j.psychres.2019.05.015DOI Listing
June 2019

HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis.

J Allergy Clin Immunol 2019 06 20;143(6):2120-2130. Epub 2018 Dec 20.

St John's Institute of Dermatology, Faculty of Life Sciences & Medicine, London, United Kingdom. Electronic address:

Background: Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection could improve patient outcomes and treatment cost-effectiveness.

Objective: We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti-TNF-α) and ustekinumab (anti-IL-12/23).

Methods: This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*06:02 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables.

Results: HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio [OR], 2.95; P = 5.85 × 10), and the difference was greater in HLA-C*06:02-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10). Biologic-naive patients who were HLA-C*06:02 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10). Results from HLA-wide analyses were consistent with HLA-C*06:02 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*06:02 and ERAP1.

Conclusion: This large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.
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http://dx.doi.org/10.1016/j.jaci.2018.11.038DOI Listing
June 2019

A Case of Concomitant Pemphigus Foliaceus and Oral Pemphigus Vulgaris.

Head Neck Pathol 2018 Dec 16;12(4):592-597. Epub 2018 Jan 16.

Oral Medicine Unit, Charles Clifford Dental Hospital, 76 Wellesley Road, Sheffield, S10 2SZ, UK.

Pemphigus is a chronic autoimmune condition that can affect multiple areas of the body. The two main subtypes of pemphigus are pemphigus vulgaris (PV) and pemphigus foliaceus (PF) which can rarely occur concurrently or even transition from one to the other. The process of transition may be explained by qualitative changes in desmoglein autoantibody profile. We present a rare case of concomitant PF and oral PV and explore the literature on transitions between pemphigus subtypes and whether this case could represent a transition from PF to PV. Furthermore, the realities of multidisciplinary patient management are discussed.
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http://dx.doi.org/10.1007/s12105-017-0884-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232195PMC
December 2018

Adalimumab, etanercept and ustekinumab for treating plaque psoriasis in children and young people: systematic review and economic evaluation.

Health Technol Assess 2017 11;21(64):1-244

Centre for Health Economics, University of York, York, UK.

Background: Psoriasis is a chronic inflammatory disease that predominantly affects the skin. Adalimumab (HUMIRA, AbbVie, Maidenhead, UK), etanercept (Enbrel, Pfizer, New York, NY, USA) and ustekinumab (STELARA, Janssen Biotech, Inc., Titusville, NJ, USA) are the three biological treatments currently licensed for psoriasis in children.

Objective: To determine the clinical effectiveness and cost-effectiveness of adalimumab, etanercept and ustekinumab within their respective licensed indications for the treatment of plaque psoriasis in children and young people.

Data Sources: Searches of the literature and regulatory sources, contact with European psoriasis registries, company submissions and clinical study reports from manufacturers, and previous National Institute for Health and Care Excellence (NICE) technology appraisal documentation.

Review Methods: Included studies were summarised and subjected to detailed critical appraisal. A network meta-analysis incorporating adult data was developed to connect the effectiveness data in children and young people and populate a de novo decision-analytic model. The model estimated the cost-effectiveness of adalimumab, etanercept and ustekinumab compared with each other and with either methotrexate or best supportive care (BSC), depending on the position of the intervention in the management pathway.

Results: Of the 2386 non-duplicate records identified, nine studies (one randomised controlled trial for each drug plus six observational studies) were included in the review of clinical effectiveness and safety. Etanercept and ustekinumab resulted in significantly greater improvements in psoriasis symptoms than placebo at 12 weeks' follow-up. The magnitude and persistence of the effects beyond 12 weeks is less certain. Adalimumab resulted in significantly greater improvements in psoriasis symptoms than methotrexate for some but not all measures at 16 weeks. Quality-of-life benefits were inconsistent across different measures. There was limited evidence of excess short-term adverse events; however, the possibility of rare events cannot be excluded. The majority of the incremental cost-effectiveness ratios for the use of biologics in children and young people exceeded NICE's usual threshold for cost-effectiveness and were reduced significantly only when combined assumptions that align with those made in the management of psoriasis in adults were adopted.

Limitations: The clinical evidence base for short- and long-term outcomes was limited in terms of total participant numbers, length of follow-up and the absence of young children.

Conclusions: The paucity of clinical and economic evidence to inform the cost-effectiveness of biological treatments in children and young people imposed a number of strong assumptions and uncertainties. Health-related quality-of-life (HRQoL) gains associated with treatment and the number of hospitalisations in children and young people are areas of considerable uncertainty. The findings suggest that biological treatments may not be cost-effective for the management of psoriasis in children and young people at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year, unless a number of strong assumptions about HRQoL and the costs of BSC are combined. Registry data on biological treatments would help determine safety, patterns of treatment switching, impact on comorbidities and long-term withdrawal rates. Further research is also needed into the resource use and costs associated with BSC. Adequately powered randomised controlled trials (including comparisons against placebo) could substantially reduce the uncertainty surrounding the effectiveness of biological treatments in biologic-experienced populations of children and young people, particularly in younger children. Such trials should establish the impact of biological therapies on HRQoL in this population, ideally by collecting direct estimates of EuroQol-5 Dimensions for Youth (EQ-5D-Y) utilities.

Study Registration: This study is registered as PROSPERO CRD42016039494.

Funding: The National Institute for Health Research Health Technology Assessment programme.
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http://dx.doi.org/10.3310/hta21640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5694897PMC
November 2017

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research.

Ann Rheum Dis 2018 02 30;77(2):241-250. Epub 2017 Oct 30.

Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.

Objectives: This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres.

Methods: A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process. Exploiting Delphi methodology, two web-based questionnaires were distributed to healthcare professionals caring for patients with JDM identified through email distribution lists of international paediatric rheumatology and myositis research groups. A separate questionnaire was sent to parents of children with JDM and patients with JDM, identified through established research networks and patient support groups. The results of these parallel processes informed a face-to-face nominal group consensus meeting of international myositis experts, tasked with defining the content of the dataset. This developed dataset was tested in routine clinical practice before review and finalisation.

Results: A dataset containing 123 items was formulated with an accompanying glossary. Demographic and diagnostic data are contained within form A collected at baseline visit only, disease activity measures are included within form B collected at every visit and disease damage items within form C collected at baseline and annual visits thereafter.

Conclusions: Through a robust international process, a consensus dataset for JDM has been formulated that can capture disease activity and damage over time. This dataset can be incorporated into national and international collaborative efforts, including existing clinical research databases.
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http://dx.doi.org/10.1136/annrheumdis-2017-212141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816738PMC
February 2018

Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

J Invest Dermatol 2018 03 17;138(3):534-541. Epub 2017 Oct 17.

Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, Manchester, UK. Electronic address:

Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9 (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR = 1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis.
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http://dx.doi.org/10.1016/j.jid.2017.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5832757PMC
March 2018

Safety of Systemic Agents for the Treatment of Pediatric Psoriasis.

JAMA Dermatol 2017 11;153(11):1147-1157

Department of Dermatology, Northwestern University, Chicago, Illinois.

Importance: Use of systemic therapies for moderate to severe psoriasis in children is increasing, but comparative data on their use and toxicities are limited.

Objective: To assess patterns of use and relative risks of systemic agents for moderate to severe psoriasis in children.

Design, Setting, And Participants: A retrospective review was conducted at 20 centers in North America and Europe, and included all consecutive children with moderate to severe psoriasis who used systemic medications or phototherapy for at least 3 months from December 1, 1990, to September 16, 2014.

Main Outcomes And Measures: The minimal core data set included age, sex, severity of psoriasis, systemic interventions, monitoring, adverse events (AEs), and reason for discontinuation.

Results: For 390 children (203 girls and 187 boys; mean [SD] age at diagnosis, 8.4 [3.7] years) with psoriasis who used 1 or more systemic medications, the mean interval between diagnosis and starting systemic therapy was 3.0 years. Methotrexate was used by 270 patients (69.2%), biologic agents (primarily etanercept) by 106 (27.2%), acitretin by 57 (14.6%), cyclosporine by 30 (7.7%), fumaric acid esters by 19 (4.9%), and more than 1 medication was used by 73 (18.7%). Of 270 children taking methotrexate, 130 (48.1%) reported 1 or more AEs associated with methotrexate, primarily gastrointestinal (67 [24.8%]). Folic acid 6 days per week (odds ratio, 0.16; 95% CI, 0.06-0.41; P < .001) or 7 days per week (OR, 0.21; 95% CI, 0.08-0.58; P = .003) protected against gastrointestinal AEs more than once-weekly folic acid, regardless of the total weekly dosage. Methotrexate-associated hepatic transaminase elevations were associated with obesity (35 of 270 patients [13.0%]), but a folic acid regimen was not. Injection site reactions occurred in 20 of 106 patients (18.9%) treated with tumor necrosis factor inhibitors, but did not lead to discontinuation of treatment. Having 1 or more AEs related to medication, gastrointestinal AE, laboratory abnormality, or AE leading to discontinuation of the drug was more likely with methotrexate than tumor necrosis factor inhibitors, but having 1 or more infections related to medication (predominantly upper airway) was less likely. Six patients developed a serious treatment-related AE (methotrexate, 3; fumaric acid esters, 2; and adalimumab, 1), but methotrexate and biologic agents were taken for a mean duration that was 2-fold greater than the mean duration for cyclosporine or fumaric acid esters. No patient developed tuberculosis or a malignant neoplasm.

Conclusions And Relevance: Medication-related AEs occur less often with tumor necrosis factor inhibitors than with methotrexate. Folic acid administration 6 or 7 times per week protected more against methotrexate-induced gastrointestinal AEs than did weekly administration. A prospective registry is needed to track the long-term risks of systemic agents for pediatric psoriasis.
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http://dx.doi.org/10.1001/jamadermatol.2017.3029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710436PMC
November 2017

Re: Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis.

J Invest Dermatol 2017 12 31;137(12):2644-2646. Epub 2017 Aug 31.

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust & King's College, London, UK. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2017.07.848DOI Listing
December 2017

True communication skills assessment in interdepartmental OSCE stations: Standard setting using the MAAS-Global and EduG.

Patient Educ Couns 2018 Jan 11;101(1):147-151. Epub 2017 Jul 11.

School of Medicine, College of Medicine, Nursing & Health Sciences, National University of Ireland, Galway, Ireland. Electronic address:

Background: Comparing outcome of clinical skills assessment is challenging. This study proposes reliable and valid comparison of communication skills (1) assessment as practiced in Objective Structured Clinical Examinations (2). The aim of the present study is to compare CS assessment, as standardized according to the MAAS Global, between stations in a single undergraduate medical year.

Methods: An OSCE delivered in an Irish undergraduate curriculum was studied. We chose the MAAS-Global as an internationally recognized and validated instrument to calibrate the OSCE station items. The MAAS-Global proportion is the percentage of station checklist items that can be considered as 'true' CS. The reliability of the OSCE was calculated with G-Theory analysis and nested ANOVA was used to compare mean scores of all years.

Results: MAAS-Global scores in psychiatry stations were significantly higher than those in other disciplines (p<0.03) and above the initial pass mark of 50%. The higher students' scores in psychiatry stations were related to higher MAAS-Global proportions when compared to the general practice stations.

Conclusion: Comparison of outcome measurements, using the MAAS Global as a standardization instrument, between interdisciplinary station checklists was valid and reliable.

Practice Implications: The MAAS-Global was used as a single validated instrument and is suggested as gold standard.
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http://dx.doi.org/10.1016/j.pec.2017.07.003DOI Listing
January 2018

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis.

J Invest Dermatol 2017 08 27;137(8):1646-1654. Epub 2017 Apr 27.

St John's Institute of Dermatology, Guy's and St. Thomas' NHS Foundation Trust, London, UK. Electronic address:

Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).
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http://dx.doi.org/10.1016/j.jid.2017.04.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519491PMC
August 2017

Neuropsychiatric syndromes of multiple sclerosis.

J Neurol Neurosurg Psychiatry 2017 08 11;88(8):697-708. Epub 2017 Mar 11.

Department of Psychiatry, National University of Ireland, Galway, Ireland.

Neuropsychiatric signs and symptoms occur frequently in individuals with multiple sclerosis (MS), either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and the treatments of MS can adversely impact an individual's mental health. In this review, we discuss the common neuropsychiatric syndromes that occur in MS and describe the clinical symptoms, aetiology, neuroimaging findings and management strategies for these conditions.
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http://dx.doi.org/10.1136/jnnp-2016-315367DOI Listing
August 2017

Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis.

J Invest Dermatol 2016 08 13;136(8):1584-1591. Epub 2016 Apr 13.

Dermatology Centre, Salford Royal NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Electronic address:

A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12-16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36-1.41) and weeks 20-30 (odds ratio = 2.27, 95% confidence interval = 0.45-11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47-4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world.
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http://dx.doi.org/10.1016/j.jid.2016.03.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946794PMC
August 2016

Systemic therapy for vulval Erosive Lichen Planus (the 'hELP' trial): study protocol for a randomised controlled trial.

Trials 2016 Jan 4;17. Epub 2016 Jan 4.

Centre of Evidence Based Dermatology, University of Nottingham, King's Meadow Campus, Lenton Lane, NG7 2NR, Nottingham, UK.

Background: Erosive lichen planus affecting the vulva (ELPV) is a relatively rare, chronic condition causing painful raw areas in the vulvovaginal region. Symptoms are pain and burning, which impact upon daily living. There is paucity of evidence regarding therapy. A 2012 Cochrane systematic review found no randomised controlled trials (RCTs) in this field. Topically administered corticosteroids are the accepted first-line therapy: however, there is uncertainty as to which second-line treatments to use. Several systemic agents have been clinically noted to show promise for ELPV refractory to topically administered corticosteroids but there is no RCT evidence to support these. The 'hELP' study is a RCT with an internal pilot phase designed to provide high-quality evidence.

Methods/design: The objective is to test whether systemic therapy in addition to standard topical therapy is a beneficial second-line treatment for ELPV. Adjunctive systemic therapies used are hydroxychloroquine, methotrexate, mycophenolate mofetil and prednisolone. Topical therapy plus a short course of prednisolone given orally is considered the comparator intervention. The trial is a four-armed, open-label, pragmatic RCT which uses a blinded independent clinical assessor. To provide 80 % power for each comparison, 96 participants are required in total. The pilot phase aims to recruit 40 participants. The primary clinical outcome is the proportion of patients achieving treatment success at 6 months. 'Success' is defined by a composite measure of Patient Global Assessment score of 0 or 1 on a 4-point scale plus improvement from baseline on clinical photographs scored by a clinician blinded to treatment allocation. Secondary clinical outcomes include 6-month assessment of: (1) Reduction in pain/soreness; (2) Global assessment of disease; (3) Response at other affected mucosal sites; (4) Hospital Anxiety and Depression Scale scores; (5) Sexual function; (6) Health-related quality of life using 'Short Form 36' and 'Skindex-29' questionnaires; (7) Days of topical steroid use; (8) Treatment satisfaction; (9) Discontinuation of medications due to treatment failure; (10) Per participant cost of intervention in each treatment group. Adverse events will also be reported.

Discussion: 'hELP' is the first RCT to address second-line treatment of ELPV. The trial has encountered unique methodological challenges and has required collaborative efforts of the UK Dermatology Clinical Trials Network alongside expert clinicians.

Trial Registration:

Current Controlled Trials: ISRCTN 81883379 . Date of registration 12 June 2014.
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http://dx.doi.org/10.1186/s13063-015-1133-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4698814PMC
January 2016

Anti-TNF agents for paediatric psoriasis.

Cochrane Database Syst Rev 2015 Nov 24(11):CD010017. Epub 2015 Nov 24.

Grupo de Investigación Dermatológica (GRID), Universidad de Antioquia, Carrera 25 A #1 A Sur 45, Of 733, Torre Medica El Tesoro, Medellín, Colombia.

Background: Psoriasis is a chronic skin disease that may develop at any age. Estimates for the United States and Europe suggest that psoriasis accounts for 4% of skin diseases in children. In most cases, the condition is mild and can be treated with creams. However, a small percentage of children have moderate to severe disease that requires drugs, such as ciclosporin or methotrexate, and some will require injections with newer biological agents, such as anti-TNF (tumour necrosis factor) drugs. Anti-TNF drugs (among them etanercept, infliximab, and adalimumab) are designed to reduce inflammation in the body caused by tumour necrosis factor. Evidence for the safety and efficacy of these biological agents in paediatric psoriasis is lacking.

Objectives: To assess the efficacy and safety of anti-TNF agents for the treatment of paediatric psoriasis.

Search Methods: We searched the following databases up to July 2015: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), and LILACS (from 1982). We also searched 13 trials registers and checked the reference lists of included studies and key review articles for further references to relevant randomised controlled trials (RCTs). We handsearched conference proceedings and attempted to contact trial authors and relevant pharmaceutical manufacturers. We searched the US Food and Drug Administration's and European Medicines Agency's adverse effects databases.

Selection Criteria: All relevant RCTs that evaluated the efficacy and safety of anti-TNF agents for the treatment of chronic plaque psoriasis in individuals less than 18 years of age.

Data Collection And Analysis: Two review authors independently checked titles and abstracts and performed data extraction and 'Risk of bias' assessment of the included studies. One review author entered data into Review Manager (RevMan), and a second review author checked the data. We also attempted to obtain unclear data from the trial authors where possible.Our primary outcomes were investigator-assessed number of participants achieving a 75% improvement in Psoriasis Area and Severity Index-75 (PASI 75) compared to baseline, improvement in quality of life using an instrument such as Children's Dermatology Life Quality Index (CDLQI), and adverse effects. Our secondary outcomes included the proportion of participants achieving PASI 50 and the Physician's Global Assessment (PGA).

Main Results: We included one study with 211 participants (median age 13 years), in which etanercept (dosage ranged from 0.8 to 50 mg per kilogram of body weight) was compared to placebo. Follow-up was over a 48-week period.At week 12, 57% versus 11% who received etanercept or placebo, respectively, achieved the PASI 75 (risk ratio 4.95, 95% confidence interval (CI) 2.83 to 8.65; high-quality evidence). Absolute risk reduction and the number needed to treat to obtain a benefit with etanercept was 45% (95% CI 33.95 to 56.40) and 2 (95% CI 1.77 to 2.95), respectively.The percentage improvement from baseline of the CDLQI scores at week 12 was better in the etanercept group than the placebo group (52.3% versus 17.5%, respectively (P = 0.0001)). Analysis between the groups showed an effect size that was clinically important (mean difference 2.30, 95% CI 0.85 to 3.75; high-quality evidence). However, means, medians, and minimal important difference results and results of the Pediatric Quality of Life Inventory, Stein Impact on Family Scale, and Harter Self-Perception Profile for Children scores must be interpreted with caution, as they were not prespecified outcomes.Three serious adverse events were reported, but they were resolved without sequelae. Deaths or other events such as malignant tumours, opportunistic infections, tuberculosis, or demyelination were not reported in the included study.Also, 13% of participants in the placebo group and 53% in the etanercept group had a PGA of clear or almost clear (risk ratio 3.96, 95% CI 2.36 to 6.66; high-quality evidence) at week 12.

Authors' Conclusions: This review found only one RCT evaluating the use of this type of biological therapy. Although the risk of publication bias was high, as we included only one industry-sponsored RCT, the risk of allocation, selection, performance, attrition, and selective reporting biases for all outcomes (except for CDLQI) was low, and no short-term serious adverse events were found.We can conclude, based on this single included study, that etanercept seems to be efficacious and safe (at least in the short term) for the treatment of paediatric psoriasis. However, as the GRADE approach refers not to individual studies but to a body of evidence, we shall wait for the results of the ongoing studies in a future update of this review. In addition, future studies should evaluate quality-of-life endpoints established a priori and standardise primary outcome measures such as PASI 75, and should include the PGA as a secondary endpoint. Also, collating and reporting adverse events uniformly is required to better evaluate safety.
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http://dx.doi.org/10.1002/14651858.CD010017.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6493213PMC
November 2015

Clozapine-induced stuttering: an estimate of prevalence in the west of Ireland.

Ther Adv Psychopharmacol 2015 Aug;5(4):232-6

Department of Psychiatry, National University of Ireland Galway, Galway, Ireland.

Objectives: Clozapine is the most effective treatment available for treatment-resistant schizophrenia; however, it is also associated with a large array of adverse effects that limits its tolerability. A number of previous case reports have noted an association between clozapine and stuttering, however the rate of this possible adverse effect is yet to be established.

Methods: In this paper, we present six cases of patients treated with clozapine who developed stuttering.

Results: Clozapine was associated with stuttering in 0.92% of individuals treated with clozapine in the region. Clozapine-induced stuttering was associated with an increase in treatment dose or with dose titration at initiation of clozapine in five individuals, with dose reduction or slower dose titration associated with a cessation of stuttering in these cases.

Conclusions: This is the largest case series to date examining clozapine-induced stuttering and indicates that clozapine-induced stuttering is a relatively common adverse effect that can be managed by a slower titration of clozapine dosage or a modest reduction in dose in most cases.
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http://dx.doi.org/10.1177/2045125315590060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4535049PMC
August 2015

Mucocutaneous manifestations in juvenile-onset systemic lupus erythematosus: a review of literature.

Pediatr Rheumatol Online J 2015 5;13. Epub 2015 Jan 5.

Institute of Translational Medicine, Alder Hey Children's NHS Foundation Trust, University of Liverpool, Liverpool, UK ; Department of Women's and Children's Health, Institute of Translational Medicine, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, L12 2AP UK.

Patients diagnosed with juvenile-onset systemic lupus erythematosus (JSLE) often have skin and oral lesions as part of their presentation. These mucocutaneous lesions, as defined by the American College of Rheumatology (ACR) in 1997, include malar rash, discoid rash, photosensitivity and oral ulcers. It is therefore essential to recognize mucocutaneous lesions to accurately diagnose JSLE. The mucocutaneous lesions can be divided into those with classical histological features (LE specific) and those strongly associated with and forming part of the diagnostic spectrum, but without the classical histological changes of lupus (LE nonspecific). A malar rash is the most commonly associated LE specific dermatological presentation. This skin manifestation is an acute form and also correlates with disease activity. Subacute (polycyclic or papulosquamous lesions) and chronic (discoid lesions) forms, whilst showing classical histological changes supportive of lupus, are less commonly associated with systemic lupus and do not correlate with disease activity. The most commonly associated skin lesions without classical lupus changes are cutaneous vasculitis, oral ulcers and diffuse non-scarring alopecia. These signs frequently relate to disease activity. An understanding of cutaneous signs and symptoms of lupus in children is important to avoid delay in diagnosis. They will often improve as lupus is adequately controlled and their reappearance is often the first indicator of a disease flare.
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http://dx.doi.org/10.1186/1546-0096-13-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292833PMC
September 2015

Biological therapies for the treatment of severe psoriasis in patients with previous exposure to biological therapy: a cost-effectiveness analysis.

Pharmacoeconomics 2015 Feb;33(2):163-77

Symmetron Limited, Kinetic Centre, Theobald Street, Borehamwood, Hertfordshire, WD6 4PJ, UK,

Background: Biologic therapies have revolutionised the care of patients with psoriasis, although they come at significant extra cost. Guidance on their use in the UK National Health Service (NHS) has so far focused on patients who are "biologic naive", yet a minority of patients have poor response and require further treatment.

Objectives: To assess the potential cost effectiveness of sequential biologic therapies in patients with psoriasis who have been exposed to previous biologic therapy.

Methods: A two-part model with a 10-year time horizon was built to model an initial 13.5-week "trial" phase and a longer-term "treatment" period with annual Markov cycles. Psoriasis Area and Severity Index (PASI) response rates from subgroup analyses of three randomised placebo-controlled trials evaluating biologic agents were considered. A meta-analysis of these data provided probabilities of achieving PASI response (50/75/90) in the short term, and published evidence and assumptions were used to predict outcomes over the longer term. Benefits were measured in quality-adjusted life years (QALYs), and costs (2013-14) to the UK NHS included drugs, administration, monitoring, and hospitalisation. Costs and benefits were discounted 3.5 % per annum. Cost effectiveness of sequential biologic therapy was measured using an incremental cost-effectiveness ratio (ICER) compared to best supportive care (BSC). Extensive sensitivity analyses were performed to assess the impact of alternative assumptions on the results.

Results: Results indicate that over 10 years, switching to a second biologic following intolerance to or failure of a first is likely to generate more QALYs than BSC, but at a higher cost. Base case results suggest the ICER of the second biologic compared to BSC is £17,681 per QALY; however, sensitivity analyses indicate that changes in the efficacy of BSC, drug costs, dropout rates, and rates of hospitalisation have a significant impact, causing the ICER to range from less than £10,000 to over £50,000 per QALY.

Conclusions: Further biologic therapy for patients with psoriasis who have previously been treated with biologic therapy may be cost effective, although there is considerable uncertainty in the results. Future studies should be designed to evaluate the clinical efficacy of biologic therapies in this subgroup with particular attention given to short-term and longer-term responses.
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http://dx.doi.org/10.1007/s40273-014-0226-yDOI Listing
February 2015