Cannock Chase Hospital

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

OBJECTIVE: In patients with active rheumatoid arthritis (RA) despite methotrexate, to compare the efficacy of adding tocilizumab to that of switching to tocilizumab monotherapy. METHODS: Double-blind, 2-year study in which adults with active RA (DAS28 >4.4) despite methotrexate were randomly assigned either to continue methotrexate with the addition of tocilizumab (MTX+TCZ) 8 mg/kg every 4 weeks or switch to tocilizumab and placebo (TCZ+PBO). The primary endpoint was the DAS28-erythrocyte sedimentation rate (ESR) remission rate at week 24. Secondary objectives included other symptomatic outcomes, quality of life and progression of structural damage. RESULTS: Of 556 randomly assigned patients, 512 (92%) completed 24 weeks. DAS28-ESR remission rates were 40.4% for TCZ+MTX and 34.8% for TCZ+PBO (p=0.19); American College of Rheumatology 20/50/70/90 rates were 71.5%/45.5%/24.5%/5.8% (TCZ+MTX) and 70.3%/40.2%/25.4%/5.1% (TCZ+PBO; differences not significant). A significant difference between groups was seen for low DAS28 (61.7% vs 51.4%). Radiographic progression was small and not different between groups (Genant-Sharp score progression ≤ smallest detectable change in 91% (TCZ+MTX) and 87% (TCZ+PBO)). Rates per 100 patient-years of serious adverse events and serious infections were 21 and six, respectively, for TCZ+MTX and 18 and six, respectively, for TCZ+PBO. Alanine aminotransferase elevations greater than threefold the upper limit of normal occurred in 7.8% and 1.2% of TCZ+MTX and TCZ+PBO patients, respectively. CONCLUSION: No clinically relevant superiority of the TCZ+MTX add-on strategy over the switch to tocilizumab monotherapy strategy was observed. The combination was more commonly associated with transaminase increases. Meaningful clinical and radiographic responses were achieved with both strategies, suggesting that tocilizumab monotherapy might be a valuable treatment strategy in suitable RA patients.

This paper reports on an investigation of three interdisciplinary mental health teams. The discussion of the responses highlights the boundaries that exist between different professional roles and areas of responsibility. Whereas there is some evidence of role blurring, which was welcomed by a few respondents, others sought to preserve their own professional identity within the multidisciplinary environment. In a paradoxical sense, the lack of managerial direction and the encouragement of generic working seemed to make some respondents all the more insistent on separate professional identities. We conclude that, far from being a relic of the past or a product of 'ingrained attitudes', boundaries between professions are actively encouraged by the experience of interdisciplinary modes of working.

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441.

How to cite this article: McKenzie Y.A., Alder A., Anderson W., Wills A., Goddard L., Gulia P., Jankovich E., Mutch P., Reeves L.B., Singer A. & Lomer M.C.E. on behalf of Gastroenterology Specialist Group of the British Dietetic Association. (2012) British Dietetic Association evidence‐based practice guidelines for the dietary management of irritable bowel syndrome in adults. J Hum Nutr Diet . 25, 260–274 Abstract Background: Irritable bowel syndrome (IBS) is a chronic debilitating functional gastrointestinal disorder. Diet and lifestyle changes are important management strategies. The aim of these guidelines is to systematically review key aspects of the dietary management of IBS, with the aim of providing evidence‐based guidelines for use by registered dietitians. Methods: Questions relating to diet and IBS symptom management were developed by a guideline development group. These included the role of milk and lactose, nonstarch polysaccharides (NSP), fermentable carbohydrates in abdominal bloating, probiotics and empirical or elimination diets. A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic database search engines: Cinahl, Cochrane Library, Embase, Medline, Scopus and Web of Science. Evidence statements, recommendations, good practice points and research recommendations were developed. Results: Thirty studies were critically appraised. A dietetic care pathway was produced following a logical sequence of treatment and formed the basis of these guidelines. Three lines of dietary management were identified. First line: Clinical and dietary assessment, healthy eating and lifestyle management with some general advice on lactose and NSP. Second line: Advanced dietary interventions to improve symptoms based on NSP, fermentable carbohydrates and probiotics. Third line: Elimination and empirical diets. Research recommendations were also identified relating to the need for adequately powered and well designed randomised controlled trials. Conclusions: These guidelines provide evidence‐based details of how to achieve the successful dietary management of IBS.

OBJECTIVE: To evaluate the efficacy and tolerability of prolonged administration of quinapril, a long-acting angiotensin-converting enzyme inhibitor, in the management of the peripheral vascular manifestations of limited cutaneous systemic sclerosis (lcSSc) and in the prevention of the progression of visceral organ involvement in the disease. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study evaluating quinapril 80 mg/day, or the maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon (RP) and the presence of SSc-specific antinuclear antibodies. Treatment was for 2-3 years. The primary outcome measure was the number of new ischemic ulcers appearing on the hands; secondary measures were the frequency and severity of RP attacks, skin score, treatments for ischemia, health status (measured by the Short Form 36 instrument), measures of kidney and lung function, and echocardiographic estimates of pulmonary artery pressure. An intent-to-treat analysis was used. RESULTS: Quinapril did not affect the occurrence of digital ulcers or the frequency or severity of RP episodes. It did not alter the treatments that were prescribed for either infected ulcers or severe RP symptoms. There was no apparent effect on the estimated tricuspid gradient. Health status was not affected by quinapril, and one-half of the patients who believed they had benefited from the trial treatment were in the placebo arm. Quinapril was not tolerated by one-fifth of the patients, with dry cough being the most frequent side effect. CONCLUSION: Administration of quinapril for up to 3 years had no demonstrable effects on the occurrence of upper limb digital ulcers or on other vascular manifestations of lcSSc in this patient population.

BACKGROUND: Topical photodynamic therapy (PDT) is widely used to treat superficial nonmelanoma skin cancer and dysplasia, and is generally well tolerated. However, as with all treatments, adverse effects may occur and awareness may facilitate approaches to prevention and management. OBJECTIVES: To review the available evidence relating to the adverse effects of topical PDT, to help inform recommendations in updated clinical guidelines produced by the British Association of Dermatologists and British Photodermatology Group, and the efficacy of preventative and therapeutic approaches. METHODS: This review summarizes the published evidence related to the adverse effects of topical PDT and attempts to interpret this evidence in the context of patient risk and management. RESULTS: Pain and discomfort during PDT are acute adverse effects, which can be minimized through the use of modified and low-irradiance PDT regimens and do not therefore usually limit successful treatment delivery. Other adverse effects include the risk of contact allergy to photosensitizer prodrugs, although this is rare but should be kept in mind, particularly for patients who have received multiple PDT treatments to larger areas. There are no other significant documented longer-term risks and, to date, no evidence of cumulative toxicity or photocarcinogenic risk. CONCLUSIONS: Topical PDT is usually well tolerated, reinforcing the utility of this important therapeutic option in dermatology practice. The main acute adverse effect of pain can typically be minimized through preventative approaches of modified PDT regimens. Other adverse effects are uncommon and generally do not limit treatment delivery.

Background: Synovitis is believed to play a role in producing symptoms in persons with hand osteoarthritis, but data on slow-acting anti-inflammatory treatments are sparse. Objective: To determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment of hand osteoarthritis. Design: Randomized, double-blind, placebo-controlled clinical trial with 12-month follow-up. (ISRCTN registry number: ISRCTN91859104). Setting: 13 primary and secondary care centers in England. Participants: Of 316 patients screened, 248 participants (82% women; mean age, 62.7 years) with symptomatic (pain ≥4 on a 0- to 10-point visual analogue scale) and radiographic hand osteoarthritis were randomly assigned and 210 (84.7%) completed the 6-month primary end point. Intervention: Hydroxychloroquine (200 to 400 mg) or placebo (1:1) for 12 months with ongoing usual care. Measurements: The primary end point was average hand pain during the previous 2 weeks (on a 0- to 10-point numerical rating scale [NRS]) at 6 months. Secondary end points included self-reported pain and function, grip strength, quality of life, radiographic structural change, and adverse events. Baseline ultrasonography was done. Results: At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group, with a treatment difference of -0.16 point (95% CI, -0.73 to 0.40 point) (P = 0.57). Results were robust to adjustments for adherence, missing data, and use of rescue medication. No significant treatment differences existed at 3, 6, or 12 months for any secondary outcomes. The percentage of participants with at least 1 joint with synovitis was 94% (134 of 143) on grayscale ultrasonography and 59% on power Doppler. Baseline structural damage or synovitis did not affect treatment response. Fifteen serious adverse events were reported (7 in the hydroxychloroquine group [3 defined as possibly related] and 8 in the placebo group). Limitation: Hydroxychloroquine dosage restrictions may have reduced efficacy. Conclusion: Hydroxychloroquine was no more effective than placebo for pain relief in patients with moderate to severe hand pain and radiographic osteoarthritis. Primary Funding Source: Arthritis Research UK.

The overall objective of the guideline is to provide up‐to‐date, evidence‐based recommendations for the use of topical photodynamic therapy (PDT). The document aims to: offer an appraisal of all relevant literature up to April 2018, focusing on any key developments address important, practical clinical questions relating to the primary guideline objective and provide guideline recommendations and if appropriate research recommendations. The guideline is presented as a detailed review with highlighted recommendations for practical use in primary care and in the clinic, in addition to an updated patient information leaflet [available on the British Association of Dermatologists (BAD) website, www.bad.org.uk/leaflets]. The guideline does not cover systemically administered PDT or PDT as a treatment option for genital warts and anal intraepithelial neoplasia, as these are out of the remit of dermatology for this guideline This set of guidelines has been developed using the BAD's recommended methodology1 (see Appendix K in the Supporting Information) with reference to the Appraisal of Guidelines Research and Evaluation (AGREE II) instrument (www.agreetrust.org)2 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE).3 The recommendations were developed for implementation in the U.K. National Health Service. The Guideline Development Group (GDG) consisted of consultant dermatologists (later joined by a trainee dermatologist), a consultant physicist, a photobiology technologist, a patient and a technical team (consisting of a guideline research fellow and project manager providing methodological and technical support). The GDG established several clinical questions pertinent to the scope of the guideline and a set of outcome measures of importance to patients, ranked according to the GRADE methodology4 (see sections section 6 and section 7). A systematic literature search of the PubMed, MEDLINE, Embase, Cochrane and AMED databases was conducted to identify key articles for PDT from 1 January 2007 to April 2018; the search terms and strategies are detailed in Appendix L (see Supporting Information). Additional references relevant to the topic were also isolated from citations in the reviewed literature and the previous versions of the guidelines. Evidence from the included studies was graded according to the GRADE system (high, moderate, low or very low quality). The recommendations are based on evidence drawn from systematic reviews of the literature pertaining to the clinical questions identified. The summary of findings with forest plots (Appendix B), GRADE evidence profiles indicating the quality of evidence (Appendix E), tables Linking the Evidence To the Recommendations (Appendix D), PRISMA flow diagram (Appendix I) and list of excluded studies (Appendix J) are detailed in the Supporting Information and a separate systematic review for basal cell carcinoma (BCC).5 The strength of recommendation is expressed by the wording and symbols shown in Table 1. Strength of recommendation ratings Strength of recommendation ratings Topical PDT has been approved in over 18 countries worldwide for use in at least one nonmelanoma skin cancer (NMSC) indication. Currently, three prodrugs are licensed for use in topical PDT. These include a formulation of 5‐aminolaevulinic acid (ALA), Levulan® (DUSA Pharmaceuticals, Wilmington, MA, U.S.A.), for actinic keratosis (AK) and an esterified formulation, methyl aminolaevulinate (MAL), Metvix® (PhotoCure ASA, Oslo, Norway and Galderma, Paris, France) for AK, squamous cell carcinoma (SCC) in situ and superficial and nodular BCC. A nanoemulsion (nc‐ALA), Ameluz® (Biofrontera AG, Leverkusen, Germany), is licensed for PDT in combination with red light for the treatment of mild and moderate AK. The licensed indications are for the treatment of nonhyperkeratotic AK, SCC in situ and superficial BCC (and in certain thin, nodular BCCs) in adults. The nc‐ALA was also recently licensed for treatment of superficial and/or nodular BCC unsuitable for surgical treatment due to possible treatment‐related morbidity and/or poor cosmetic outcome in adults. Daylight PDT for AK is a recent indication. Metvix is licensed for PDT in combination with daylight, which is increasingly being used as a light source in the treatment of AK. Topical PDT is used in selected patients after considering the appropriateness, clinical efficacy, other modalities of treatment, patient age, lesion site, histology, cosmesis and patient choice. To address these issues the GDG has asked the following question in relation to the use of topical PDT in the treatment of NMSC (see Appendix A in the Supporting Information for the full review protocol). In adults with an NMSC and precancerous lesions,a what are the clinical effectiveness/efficacy, safety and tolerability of photodynamic therapy (MAL‐PDT, ALA‐PDT) compared with cryotherapy, curettage, surgical excision, topicals, laser therapy, placebo or no treatment, each alone or in combination? aIncluding AK, SCC in situ (Bowen disease), BCC (superficial, nodular and other), SCC, skin cancer prophylaxis, cutaneous T‐cell lymphoma (CTCL), intraepithelial neoplasia of the external genitalia (prostatic, vulval and extragenital), extramammary Paget disease and hyperkeratosis in organ transplant patients. Topical PDT has also been used in the treatment of a number of inflammatory conditions on an unlicensed basis. To address these issues the GDG has asked the following question in relation to the use of topical PDT in the treatment of inflammatory conditions with the following criteria (case series with at least four patients will be included). See Appendix A in the Supporting Information for the full review protocol. In adults with certain infectious and inflammatory dermatoses,b what are the clinical effectiveness/efficacy, safety and tolerability of photodynamic therapy (MAL‐PDT, ALA‐PDT) compared with standard treatment modalities, including topical therapies, systemic therapies and ultraviolet B phototherapy, control or each other. bIncluding acne, actinic cheilitis, disseminated superficial actinic porokeratosis, alopecia areata, angiofibroma, cutaneous leishmaniasis, Darier disease, erythrasma, folliculitis, fungal infections, granuloma annulare, hypertrophic scars, keratoacanthoma, lichenoid dermatoses, molluscum contagiosum, morphoea and localized scleroderma, interdigital mycoses, necrobiosis lipoidica, perioral dermatitis, photorejuvenation, porokeratosis, psoriasis, radiodermatitis, rosacea, sebaceous hyperplasia, viral warts, vulval lichen sclerosus, vulvodynia, wound healing and Zoon balanitis. The GDG also established a set of outcome measures of importance to patients (treatment) for each review question, which were agreed on by the patient representative, ranked according to the GRADE methodology.4 Data on these outcomes were extracted from the included studies (Table 2) (also see Appendices F, G and H in the Supporting Information). Outcomes ranked 7, 8 or 9 are critical for decision making; those ranked 4, 5 or 6 are important but not critical for decision making. Important outcome measures for photodynamic therapy Outcomes ranked 7, 8 or 9 are critical for decision making, those ranked 4, 5 or 6 are important but not critical for decision making and those ranked 3 are less important. BCC, basal cell carcinoma; SCC, squamous cell carcinoma. aIncluding actinic keratosis, SCC in situ, BCC (superficial, nodular and other), SCC, skin cancer prophylaxis, cutaneous T‐cell lymphoma, intraepithelial neoplasia of the external genitalia (prostatic, vulval and extragenital), extramammary Paget disease and hyperkeratosis in organ transplant patients. bIncluding acne, actinic cheilitis, disseminated superficial actinic porokeratosis, alopecia areata, angiofibroma, cutaneous leishmaniasis, Darier disease, erythrasma, folliculitis, fungal infections, granuloma annulare, hypertrophic scars, keratoacanthoma, lichenoid dermatoses, molluscum contagiosum, morphoea and localized scleroderma, interdigital mycoses, necrobiosis lipoidica, perioral dermatitis, photorejuvenation, porokeratosis, psoriasis, radiodermatitis, rosacea, sebaceous hyperplasia, viral warts, vulval lichen sclerosus, vulvodynia, wound healing and Zoon balanitis. Important outcome measures for photodynamic therapy Outcomes ranked 7, 8 or 9 are critical for decision making, those ranked 4, 5 or 6 are important but not critical for decision making and those ranked 3 are less important. BCC, basal cell carcinoma; SCC, squamous cell carcinoma. aIncluding actinic keratosis, SCC in situ, BCC (superficial, nodular and other), SCC, skin cancer prophylaxis, cutaneous T‐cell lymphoma, intraepithelial neoplasia of the external genitalia (prostatic, vulval and extragenital), extramammary Paget disease and hyperkeratosis in organ transplant patients. bIncluding acne, actinic cheilitis, disseminated superficial actinic porokeratosis, alopecia areata, angiofibroma, cutaneous leishmaniasis, Darier disease, erythrasma, folliculitis, fungal infections, granuloma annulare, hypertrophic scars, keratoacanthoma, lichenoid dermatoses, molluscum contagiosum, morphoea and localized scleroderma, interdigital mycoses, necrobiosis lipoidica, perioral dermatitis, photorejuvenation, porokeratosis, psoriasis, radiodermatitis, rosacea, sebaceous hyperplasia, viral warts, vulval lichen sclerosus, vulvodynia, wound healing and Zoon balanitis. The following recommendations and ratings were agreed upon unanimously by the core members of the GDG and patient representative. For further information on the wording used for recommendations and strength of recommendation ratings see Section 2. The evidence for recommendations is based on the studies as listed (for details and discussion of the evidence see Appendices B–F in the Supporting Information). The GDG recommendations relating to referral pathways are based on discussion and clinical experience, as evidence‐based details are not available at the time of writing. The GDG is aware of the lack of high‐quality evidence for some of these recommendations, therefore strong recommendations with an asterisk (*) are based on the available evidence, as well as consensus and specialist experience. Good practice point (GPP) recommendations are derived from informal consensus. Please note that the recommendations made in this guideline may only partly overlap with formal licensed indications for the use of topical PDT in skin, hair and nail disorders. The clinical efficacy and appropriateness of other treatment modalities should also be considered, taking into account lesion site, histology, cosmesis, patient age and patient choice. All of the recommendations listed below apply where service provision makes them practically possible to do so. R1 (GPP) Explain the potential benefits and harms of topical PDT to the patient and provide a BAD patient information leaflet (www.bad.org.uk/leaflets) for PDT before choosing the treatment. R2 (GPP) Refer to the appropriate summaries of product characteristics on the electronic Medicines Compendium when administering PDT, as there are different preparation and administration procedures for each licensed indication. R3 () Offer* topical PDT as a treatment option to people with superficial BCC, particularly for poorly healing or cosmetically sensitive skin sites, multiple lesions and large‐area lesions. R4 () Consider topical PDT for people with thin (< 2 mm) nodular BCC in situations where other treatments are not practical or are contraindicated (see R6). R5 () Offer a further cycle of PDT to patients with residual lesions where the BCCs have shown a good response to the preceding treatment. R6 () Do not offer topical PDT as a standard treatment for nodular BCC at high‐risk sites. R7 (GPP) Use red light and not that of a shorter wavelength (blue or green light, or daylight) for enhanced penetration for BCC. R8 () Offer PDT as a treatment option to people with SCC in situ, particularly for poorly healing or cosmetically sensitive skin sites, multiple lesions and large‐area lesions. R9 () Offer topical PDT as a treatment option to people with AK, particularly for cosmetically sensitive skin sites, multiple lesions and large‐area lesions. R10 () Offer a further cycle of topical PDT to patients with residual lesions where the AK lesions have shown a good response to the preceding treatment. R11 () Consider daylight PDT as a treatment option for people with mild (slightly palpable AK, more easily felt than seen; Olsen grade I) or moderate (moderately thick AK, easily felt; Olsen grade II) AK lesions where pain is likely to be an issue, particularly for confluent areas on the face or scalp. R12 () Consider combining topical PDT with other treatment modalities if feasible (e.g. imiquimod or pretreatment with ablative fractional laser) for people with thick AK lesions (very thick or obvious AK; Olsen grade III). R13 () Consider PDT as a treatment option for microinvasive SCC if surgery is contraindicated. R14 () Do not offer PDT as a treatment option for invasive SCC. R15 () Consider field PDT as prophylaxis to reduce the emergence of new lesions in people with AK or NMSC, including those with organ transplantation. R16 () Consider PDT as a treatment option for vulval intraepithelial neoplasia lesions that are: unifocal nonpigmented without associated human papillomavirus infection with lower grades of dysplasia. R17 () Consider PDT as a treatment option for erythroplasia of Queyrat, bearing in mind that pain may be a limiting factor. R18 () Consider PDT as a treatment option for CTCL, particularly for early‐stage disease, few localized lesions and challenging sites such as skinfolds. R19 () Consider PDT as a treatment option for extramammary Paget disease (EMPD) for thin or small lesions: where the Paget cell infiltrate is less dense when there is limited adnexal involvement. R20 () Consider PDT as a treatment option for EMPD either before or after surgery. R21 () Consider CO2 laser prior to PDT as a treatment option for EMPD. R22 () Consider PDT as a treatment option for acne where standard treatments are ineffective or contraindicated. R23 () Consider conventional PDT as a treatment option for cutaneous leishmaniasis, particularly in cosmetically sensitive skin sites. R24 () Consider daylight PDT as a treatment option for cutaneous leishmaniasis, bearing in mind that many treatments may be required. () Consider PDT as a treatment option for viral () Do not PDT as a treatment option for fungal () Do not PDT as a treatment option for () Consider PDT as a treatment option for actinic there is evidence to any recommendation for the alopecia areata, angiofibroma, Darier disease, folliculitis, granuloma annulare, hypertrophic scars, keratoacanthoma, lichenoid dermatoses, necrobiosis lipoidica, morphoea and localized scleroderma, perioral dermatitis, photorejuvenation, porokeratosis, radiodermatitis, rosacea, sebaceous hyperplasia, vulval lichen sclerosus, vulvodynia, wound healing and Zoon balanitis. of topical therapies with PDT for superficial or thin nodular where there is residual BCC at 3 after the cycle of PDT to include detailed of and tolerability over time and in and patient treatment for combination therapy including PDT to response in BCC. of PDT in combination with other therapies for lesions or lesions to in BCC. of conventional PDT in BCC. of the efficacy of conventional daylight PDT for AK in a by Olsen grade of AK response and at sites other than the with treatment of AK treatment of the field of of conventional daylight PDT in AK, with of response and is the efficacy and safety of daylight PDT in SCC in of PDT with and in SCC in of PDT in combination with other therapies for lesions or lesions to in SCC in of the efficacy and safety of PDT for superficial microinvasive SCC where surgery is contraindicated. for combination therapy including PDT to response in microinvasive SCC when surgery is contraindicated. for to the efficacy of PDT for vulval intraepithelial neoplasia, erythroplasia of Queyrat, anal intraepithelial neoplasia, and EMPD. measures be used to pain in patients with genital lesions with of light and and to more of for studies of the full face than face for acne, with to the of and for studies with a and of clinical findings for for studies conventional PDT with topical or placebo for cutaneous for studies daylight PDT with topical or placebo for cutaneous for studies PDT with conventional treatments for PDT is using the prodrugs and methyl is by and is by the to of the has several with the being for in treatment of a of skin lesions including BCC and SCC in situ, the (blue is also for more superficial lesions such as AK. The prodrugs are in the is and addition of the methyl the more with the to and in AK and inflammatory acne but less for the with and less pain with treatment efficacy of and is and are in SCC in situ and BCC, with less pain with PDT with is according to a treatment cycle one PDT treatment in AK and PDT treatments with a in SCC in situ and nodular and superficial BCC, with light 3 after A PDT cycle is at 3 in lesions. In a of different and have been A has been licensed for use in mild A formulation of with nc‐ALA which and skin has shown lesion than in The nc‐ALA formulation has also recently been licensed for the treatment of superficial and nodular BCC. to of prodrugs and include the use of a low in of have been by treatment with including and and are also with after for in pretreatment with fractional have also been made to topical PDT using particularly to the of using with and PDT with This studies of the use of which was and in a in NMSC and and A of PDT with topical of the placebo in in with a wound with or without of when this is prior to treatment with PDT or The topical prodrugs and have been with used in therapy and The the of a by ultraviolet a this is a and to clinical practice is The also be use of with In addition to include point (e.g. which of superficial are in combining with such as or is in to with human studies indicating for in of of and also be in a of situations including of of and of clinical In of treatment to patient A light source is that will the the of the at to the to The light used for PDT of skin lesions are laser or have the of a with and are These all light with an and are also used for PDT of AK. are the use of other light including and In the of standard procedures the use of details and are in Appendix (see Supporting Information). a few clinical studies have been out using different light more than in one but other studies to a when different light were is evidence to a treatment in which a is light pretreatment using a fractional laser may penetration of the PDT has been a treatment using light are to of the treatment. These include PDT using a and to PDT the is to use daylight as the light PDT light are with no evidence of to to the In one the to over at a of only 2 from the is important to the being to the such as the treatment and use of an into of the a in of for a wavelength of compared with also that the treatment from to for light of and and further to for due to A PDT outcome the of the appropriate or light and the of The photodynamic at the cell the PDT the of the for the compared with The prodrugs are to by the photodynamic cell and of and also In addition to the of PDT on and the inflammatory and The of PDT with multiple different are to the The following recommended to the prodrugs that are licensed for use in the for nonhyperkeratotic SCC in situ and superficial and which is the only source approved in the U.K. that is licensed for on face and recently also licensed for BCC. of administration of PDT studies may to in the to preparation is a of topical PDT of which product is being The of and with a or is without pain and does not The treatment be with for preparation or combination treatment include skin with CO2 laser or ablative fractional A of 1 thick is to the lesion and the of sites are with as full to light the of or penetration before is standard practice for conventional PDT using and the time of 3 the is with the or with This is by using red light of a of or a with a from skin to of a of with an of The for AK is one treatment, for BCC and SCC in situ is treatments used in other indications are with each indication. Daylight PDT is by the of an by lesion preparation to the treatment without a patients are to daylight for for treatment of and the of daylight be The of topical PDT is with this was a limiting for the of PDT in some pain to have and inflammatory for pain have been but many studies have multiple that treatment of lesions or particularly if there is and those on the and are associated with the of of pain than lesions or on and sites. of pain such as topical and and have or limited on the pain may be more The of PDT with (e.g. daylight has the to to a and the tolerability of the treatment. with and appropriate of PDT treatment pain no to be a limiting for patients PDT. The topical PDT is an than an as and in some patients. and are also which may for to after treatment. is a and cosmetic outcome is a of PDT in with other treatments such as to the prodrugs used in topical PDT may and this should be particularly for patients have treatment to areas and in multiple such as those with field and including patients daylight PDT. is with to patients or after should be out if to of PDT are there are isolated of invasive SCC and at sites by PDT, these are in patients with skin and any with PDT is there is no evidence of a of PDT, is and references of the of topical PDT are included in a separate In the patients with PDT is there evidence of of AK, SCC in situ and superficial BCC lesions daylight PDT for AK lesions or field at 3 after the treatment at after the treatment in situ and superficial BCC pain for patients for AK, SCC in situ or BCC lesions pain of treatment or on with cosmetic outcome at 1 moderate, good or with PDT therapy in (very or very therapy, if therapies for the or lesion in indications for which PDT is not The recommendation of is to reduce in the and to different to this recommendation may to all in the preceding (see Appendix in the Supporting Information). The document and information were made available to the BAD the British Group the British Group the and the Group for which were by the further the was for review by the of the BAD up of the Guidelines prior to for This document has been on of the BAD and is based on the available when the document was is that certain conditions may be to from the guidelines and that the of studies may some of the recommendations to be is that limited in the of the U.K. may on the of a therapy the National Health evidence of to to these guidelines should not be should to these recommendations a a of The for this set of recommendations is for where important will be updated on the BAD are very to patient for in the clinical of the patient and section of the Linking Evidence To the evidence and the and to all those on the the of has been an for Galderma, and on for and and an in a by has been an for and and an in a a ultraviolet for has to a of and from and been on an for has prior to from and for photodynamic therapy on three prior to from to the PDT from These were by the British Group in were reviewed and updated by the British Association of Dermatologists and the British Group in and This is an updated guideline for the BAD which the Guidelines of the have been are National Guideline Research and has the used by the British Association of Dermatologists to clinical guidelines. The is and to using the in the updated for a British Association of Dermatologists clinical the of the GRADE The on information on be at Appendix A protocol. Appendix B Appendix evidence Appendix Linking Evidence To Appendix GRADE evidence Appendix of included Appendix G findings for Appendix H findings for Appendix PRISMA diagram Appendix excluded from Appendix K Appendix L Appendix and Appendix and

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. TRIAL REGISTRATION NUMBER: NCT02339441.

BACKGROUND: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. METHODS: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)-European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). FINDINGS: Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47-2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). INTERPRETATION: In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response. FUNDING: UK Medical Research Council and Versus Arthritis.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

BACKGROUND: Topical photodynamic therapy (PDT) is an established treatment option for low-risk basal cell carcinoma (BCC). OBJECTIVES: To compare efficacy, cosmesis and tolerability of PDT for BCC with alternative treatments. METHODS: MEDLINE, PubMed, Embase and CENTRAL databases were searched from inception until 1 September 2017. Included studies were randomized controlled trials (RCTs) of PDT for nodular (n) and superficial (s) BCC reporting at least one of the following outcomes: clearance at 3 months and sustained at 1 or 5 years; recurrence at ≥ 1 year; cosmesis; adverse events; tolerability. RESULTS: From 2331 search results, 15 RCTs (2327 patients; 3509 BCCs) were included. PDT efficacy (5-year sustained clearance) was high but inferior to excisional surgery [nBCC pooled risk ratio (RR) 0·76; 95% confidence interval (CI) 0·63-0·91], and without re-treatment of partially responding lesions, was modestly inferior to imiquimod (sBCC: RR 0·81; 95% CI 0·70-0·95) and similar to fluorouracil (sBCC: RR 0·88; 95% CI 0·75-1·04). Five-year sustained clearance was inferior with conventional vs. fractionated PDT (sBCC: RR 0·76; 95% CI 0·68-0·84). PDT cosmesis was superior to surgery (sBCC: RR 1·68, 95% CI 1·32-2·14; nBCC: RR 1·82, 95% CI 1·19-2·80) and cryosurgery (BCC: RR 3·73, 95% CI 1·96-7·07), and without re-treatment of partially responding lesions was similar to imiquimod (sBCC: RR 1·01, 95% CI 0·85-1·19) and fluorouracil (sBCC: RR 1·04, 95% CI 0·88-1·24). Peak pain was higher but of shorter duration with PDT than topical treatments. Serious adverse reactions were rarer with PDT than imiquimod (sBCC: RR 0·05, 95% CI 0·00-0·84) and fluorouracil (sBCC: RR 0·11, 95% CI 0·01-2·04). Combination PDT regimens demonstrated reduced recurrence and improved cosmesis; however, results from these small studies were often nonsignificant. CONCLUSIONS: PDT is an effective treatment for low-risk BCC, with excellent cosmesis and safety. Imiquimod has higher efficacy than single-cycle PDT but more adverse effects. Highest efficacy is with excisional surgery. Fractionated and combination PDT options warrant further study.

Background: Contradictory evidence exists for association of hyperuricemia and kidney function. To investigate the association of hyperuricemia and kidney function decline (hyperuricemia question) and effect of urate-lowering therapies (ULTs) on kidney function (ULT question), we performed a systematic review and meta-analysis. Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to July 2020. We selected observational studies for the hyperuricemia question and controlled trials for the ULT question. Two investigators independently assessed study eligibility and abstracted the data. Risk of bias was assessed using the Newcastle–Ottawa Scale and Cochrane risk of bias tool. Meta-analysis was done using the inverse variance method and random effect model. We estimated odds ratio (OR), hazard ratio (HR), risk ratio (RR), and the mean difference (MD). Evidence certainty was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: Of 12,037 studies screened, 131 studies with 3,414,226 patients were included. Hyperuricemia was associated with a significant risk of rapid estimated glomerula filtration rate (eGFR) decline ⩾3 ml/min per 1.73 m 2 per year (OR 1.38, 95% CI 1.20–1.59; low certainty), albuminuria (OR/HR 1.94, 95% CI 1.34–2.79; very low certainty), chronic kidney disease (OR/HR 2.13, 95% CI 1.74–2.61; very low certainty), and kidney failure (HR 1.53, 95% CI 1.18–1.99; very low certainty). Compared with control, ULT use for ⩾1 year was associated with significantly more improved eGFR (MD 1.81 ml/min per 1.73 m 2 , 95% CI 0.26–3.35; very low certainty), serum creatinine (MD −0.33 mg/dl, 95% CI −0.47 to −0.19; low certainty), and proteinuria (MD −5.44 mg/day, 95% CI −8.49 to −2.39; low certainty), but no difference in kidney failure. Conclusion: Hyperuricemia is associated with worsening eGFR, albuminuria, chronic kidney disease, and kidney failure. ULT use for ⩾1 year may improve kidney function. Registration: The protocol was registered at PROSPERO database, CRD42015013859.

OBJECTIVE: Patients with rheumatoid arthritis (RA) should start treatment early with the aim of suppressing the inflammatory process completely. It is not known if this strategy should, or can, be continued in later disease. METHODS: In a multicentre, randomized, observer-blinded, controlled trial, 466 patients with established RA (>5 yr), on stable therapy for at least 6 months, were randomized to adequate symptom control/shared care setting (SCSC) or aggressive treatment/hospital setting (ATH). All were reviewed annually by a rheumatologist. The primary outcome after 3 yr was the Health Assessment Questionnaire (HAQ). Others included the OMERACT core set and the Disease Activity Score (DAS) 28. RESULTS: Three hundred and ninety-nine patients completed the trial. There was a significant deterioration in HAQ in both arms. Only the physician global score differed between the arms. CONCLUSIONS: The trial showed no additional benefit of intensified treatment with traditional disease modifying anti-rheumatic drugs (DMARDs) in patients with stable, established RA. It proved hard to suppress C-reactive protein levels. Patients in the SCSC arm were able to initiate treatment changes when their symptoms deteriorated without frequent hospital assessment. Pending further evidence, the model of shared care with annual hospital review is as good as 4-monthly hospital review for these patients.

The Mayo Conservative Hip femoral prosthesis has been designed to optimise proximal femoral loading as well as preserving proximal femoral bone stock. Between October 2003 and May 2006, 42 patients (49 hips) underwent total hip replacement (THR) using the Mayo Conservative Hip femoral component. The mean age at operation was 57.8 years (range 44 to 74) and the mean clinical follow up was 3.1 years (range 2.3 to 4.7 years). The aim of our study was to review the short term results of this unorthodox femoral component. We found that 18% degrees of stems were malaligned >or= 5 degrees and the prevalence of intra-operative femoral fracture was 4%. We feel this prosthesis is difficult to implant and has an unacceptable fracture rate.

Background Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. Objective To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. Design Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. Setting Sixteen UK hospitals – participants were recruited from primary and secondary care and the community. Participants Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. Interventions Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. Main outcome measures The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment (‘a lot less noticeable’ or ‘no longer noticeable’ on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). Results In total, 517 participants were randomised (adults,n = 398; and children,n = 119; 52% male; 57% paler skin types I–III, 43% darker skin types IV–VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment ‘success’ was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%;p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval –4.4% to 14.9%;p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). Limitations Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. Conclusion Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. Future work Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. Trial registration Current Controlled Trials ISRCTN17160087. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information.

OBJECTIVE: Although drug survival time might be a better measure of clinical effectiveness than drug adherence, there is little research literature in this area, in particular about the influence of medication beliefs and psychosocial factors. This study aimed to investigate the above relationships using patients who were newly diagnosed with rheumatoid arthritis (RA). METHODS: Sixty-eight RA patients starting their first disease-modifying anti-rheumatic drug (DMARD) were interviewed shortly after initiating therapy, and then one year later. Before each meeting, patients were asked to complete a set of questionnaires, including Beliefs about Medication, Spielberger State-Trait Anxiety Inventory - Short Form, the modified Stanford Health Assessment Questionnaire, Beck Depression Inventory-1 and the Significant Others Scale. Relevant sociodemographic background, disease activity and drug history were obtained. Clinical measures such as grip strength and joint count were assessed. RESULTS: A stepwise logistic regression analysis was applied to two patient groups: those who continued taking their DMARD one year later, and those who did not. No significant difference between the groups for levels of disability and disease activity were found. Only age and anxiety emerged as significant predictors of drug discontinuation at 52 weeks. CONCLUSIONS: Contrary to expectation, this study demonstrated that older and less anxious patients were more likely to discontinue taking their initial DMARD within the first year. The study may have implications for counselling older and less anxious patients prior to DMARD therapy. However, there are limitations in generalizing the results because of the small population sample. It also did not take into account drug intolerance as a pertinent factor for early drug discontinuation.

Cerebral malaria is a significant cause of childhood morbidity in our region. The challenges of effective management include time and quality of treatment. The study appraised the health care seeking behavior of caregivers of sick children who developed cerebral malaria, in Zaria, northwestern Nigeria. Caregivers indentified were parents 29 (87.9%) and grandparents 4 (12.1%). Most of them were in the upper social classes. Health care options utilized before presentation at our facility were formal health facility 24 (72.7%), patent medicine seller 12 (36.4%), home treatment 10 (30.3%), and herbal concoction 6 (18.2%) with majority 24 (72.7%) using more than one option. Antimalarial therapy was instituted in 25 (75.6%) of the cases. Mortality was significantly associated with the use of herbal concoction, treatment at a formal health facility and patent medicine seller, multiple convulsions, age less than 5 years, and noninstitution of antimalarial therapy before presentation. The study showed use of inappropriate health care options by caregivers and highlighted the need to pursue an awareness drive among caregivers on the use of health care options.