Showing papers by "John R. Ingram published in 2015"

Interventions for hidradenitis suppurativa

Abstract: Background Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterised by recurrent painful boils in flexural sites, such as the axillae and groin, that affects about 1% of the population, with onset in early adulthood. Objectives To assess the effects of interventions for HS in people of all ages. Search methods We searched the following databases up to 13 August 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five trials registers and handsearched the conference proceedings of eight dermatology meetings. We checked the reference lists of included and excluded studies for further references to relevant trials. Selection criteria Randomised controlled trials (RCTs) of all interventions for hidradenitis suppurativa. Data collection and analysis Two review authors independently assessed study eligibility and methodological quality and performed data extraction. Our primary outcomes were quality of life, measured by a validated dermatology‐specific scale, and adverse effects of the interventions. Main results Twelve trials, with 615 participants, met our inclusion criteria. The median number of participants in each trial was 27, and median trial duration was 16 weeks. The included studies were conducted over a 32‐year time period, from 1983 to 2015. A single RCT that was underpowered to detect clinically meaningful differences investigated most interventions. There were four trials of anti‐TNF‐α (tumour necrosis factor‐alpha) therapies, which included etanercept, infliximab, and adalimumab. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) score in participants with moderate to severe HS by 4.0 points relative to placebo (95% confidence interval (CI) ‐6.5 to ‐1.5 points), an effect size approximately equal to the DLQI minimal clinically important difference. We reduced the evidence quality to 'moderate' because the effect size was based on the results of only one study. In a meta‐analysis of two studies with 124 participants, standard dose adalimumab 40 mg every other week was ineffective compared with placebo (moderate quality evidence). In a smaller study of 38 participants, of whom only 33 provided efficacy data, infliximab 5 mg/kg treatment improved DLQI by 8.4 DLQI points after eight weeks. Etanercept 50 mg twice weekly was well tolerated but ineffective. In a RCT of 200 participants, no difference was found in surgical complications (week one: risk ratio (RR) 0.78, 95% CI 0.58 to 1.05, moderate quality evidence) or risk of recurrence (after three months: RR 0.96, 95% CI 0.68 to 1.34, moderate quality evidence) in those randomised to receive a gentamicin‐collagen sponge prior to primary closure compared with primary closure alone. RCTs of other interventions, including topical clindamycin 1% solution; oral tetracycline; oral ethinylestradiol 50 mcg with either cyproterone acetate 50 mg or norgestrel 500 mcg; intense pulsed light; neodymium‐doped yttrium aluminium garnet (Nd:YAG) laser; methylene blue gel photodynamic therapy; and staphage lysate, were relatively small studies, preventing firm conclusions due to imprecision. Authors' conclusions Many knowledge gaps exist in RCT evidence for HS. Moderate quality evidence exists for adalimumab, which improves DLQI score when 40 mg is given weekly, twice the standard psoriasis dose. However, the 95% confidence interval includes an effect size of only 1.5 DLQI points, which may not be clinically relevant, and the safety profile of weekly dosing has not been fully established. Infliximab also improves quality of life, based on moderate quality evidence. More RCTs are needed in most areas of HS care, particularly oral treatments and the type and timing of surgical procedures. Outcomes should be validated, ideally, including a minimal clinically important difference for HS.

Oral fumaric acid esters for psoriasis

Abstract: Background: Psoriasis is a chronic inflammatory skin condition that can markedly reduce life quality. Several systemic therapies exist for moderate to severe psoriasis, including oral fumaric acid esters (FAE). These contain dimethyl fumarate (DMF), the main active ingredient, and monoethyl fumarate. FAE are licensed for psoriasis in Germany but used off-licence in many countries. Objectives: To assess the effects and safety of oral fumaric acid esters for psoriasis. Search methods: We searched the following databases up to 7 May 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 4, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials. We handsearched six conference proceedings that were not already included in the Cochrane Skin Group Specialised Register. Selection criteria: Randomised controlled trials (RCTs) of FAE, including DMF monotherapy, in individuals of any age and sex with a clinical diagnosis of psoriasis. Data collection and analysis: Two review authors independently assessed trial quality and extracted data. Primary outcomes were improvement in Psoriasis Area and Severity Index (PASI) score and the proportion of participants discontinuing treatment due to adverse effects. Main results: We included 6 studies (2 full reports, 2 abstracts, 1 brief communication, and 1 letter), with a total of 544 participants. Risk of bias was unclear in several studies because of insufficient reporting. Five studies compared FAE with placebo, and one study compared FAE with methotrexate. All studies reported data at 12 to 16 weeks, and we identified no longer-term studies. When FAE were compared with placebo, we could not perform meta-analysis for the primary outcome of PASI score because the three studies that assessed this outcome reported the data differently, although all studies reported a significant reduction in PASI scores with FAE. Only 1 small study designed for psoriatic arthritis reported on the other primary outcome of participants discontinuing treatment due to adverse effects (2 of 13 participants on FAE compared with none of the 14 participants on placebo; risk ratio (RR) 5.36, 95% confidence interval (CI) 0.28 to 102.1; 27 participants; very low-quality evidence). However, these findings are uncertain due to indirectness and a very wide confidence interval. Two studies, containing 247 participants and both only reported as abstracts, allowed meta-analysis for PASI 50, which showed superiority of FAE over placebo (RR 4.55, 95% CI 2.80 to 7.40; low-quality evidence), with a combined PASI 50 of 64% in those given FAE compared with a PASI 50 of 14% for those on placebo, representing a number needed to treat to benefit of 2. The same studies reported more participants achieving PASI 75 with FAE, but we did not pool the data because of significant heterogeneity; none of the studies measured PASI 90. One study reported significant improvement in participants' quality of life (QoL) with FAE, measured with Skindex-29. However, we could not compute the mean difference because of insufficient reporting in the abstract. More participants experienced adverse effects, mainly gastrointestinal disturbance and flushing, on FAE (RR 4.72, 95% CI 2.45 to 9.08; 1 study, 99 participants; moderate-quality evidence), affecting 76% of participants given FAE and 16% of the placebo group (representing a number needed to treat to harm of 2). The other studies reported similar findings or did not report adverse effects fully. One study of 54 participants compared methotrexate (MTX) with FAE. PASI score at follow-up showed superiority of MTX (mean Difference (MD) 3.80, 95% CI 0.68 to 6.92; 51 participants; very low-quality evidence), but the difference was not significant after adjustment for baseline disease severity. The difference between groups for the proportion of participants who discontinued treatment due to adverse effects was uncertain because of imprecision (RR 0.19, 95% CI 0.02 to 1.53; 1 study, 51 participants; very low-quality evidence). Overall, the number of participants experiencing common nuisance adverse effects was not significantly different between the 2 groups, with 89% of the FAE group affected compared with 100% of the MTX group (RR 0.89, 95% CI 0.77 to 1.03; 54 participants; very low-quality evidence). Flushing was more frequent in those on FAE, with 13 out of 27 participants affected compared with 2 out of 27 given MTX. There was no significant difference in the number of participants who attained PASI 50, 75, and 90 in the 2 groups (very low-quality evidence) whereas this study did not measure the effect of treatments on QoL. The included studies reported no serious adverse effects of FAE and were too small and of limited duration to provide evidence about rare or delayed effects. Authors' conclusions: Evidence suggests that FAE are superior to placebo and possibly similar in efficacy to MTX for psoriasis; however, the evidence provided in this review was limited, and it must be noted that four out of six included studies were abstracts or brief reports, restricting study reporting. FAE are associated with nuisance adverse effects, including flushing and gastrointestinal disturbance, but short-term studies reported no serious adverse effects.

Management of hidradenitis suppurativa: a U.K. survey of current practice.

Abstract: DEAR EDITOR, Management of hidradenitis suppurativa (HS; also known as acne inversa) remains a challenge owing to a combination of multiple treatment options and, until recently, a relative lack of published guidelines to assist treatment choices. More than 30 interventions are currently available, while the evidence base to support many of the interventions is weak, as highlighted by a recent HS Priority Setting Partnership. It was hypothesized that considerable variation may exist in current U.K. management of HS. To investigate this, an online survey was made available to the membership of the U.K. Dermatology Clinical Trials Network and British Association of Dermatologists between 1 November and 5 December 2014. There were 134 responses, including 88 from consultant dermatologists, 15 from dermatology registrars (residents), 14 from associate specialists, nine from dermatology specialist nurses and eight from general practitioners. Respondents were located in England, Wales, Scotland and Northern Ireland. Thirty-seven per cent saw three or more new patients with HS each month and 68% had at least six patients with HS under current follow-up. Two clinicians each saw > 50 patients with HS for regular review. In terms of topical therapy, antiseptics were routinely used by 88% of respondents and topical antibiotics were prescribed by 67%. A few clinicians used topical retinoids and three prescribed potent topical corticosteroids for disease flares. Resorcinol peels were not prescribed by any of the respondents. Clinicians were asked to select their most frequently used nontopical interventions for moderate-to-severe HS from a list of 30 options, and to rank these from first to tenth choice. A further option was offered to give details of any other therapy not included in the list. One hundred and seventeen individuals provided a response. Oral tetracyclines were the most frequently prescribed first-line therapy and were the first choice for 75% of clinicians. Most gave lymecycline or doxycycline, and 25% prescribed more than the dose recommended for acne, typically giving double the standard dose. A combination of clindamycin and rifampicin was used as the first-choice treatment by 12% of clinicians and as the second-choice treatment by 43%, representing the most frequently used second-line systemic intervention. The dosage of both antibiotics was 300 mg twice daily for 96% of respondents, and 74% gave a treatment duration of between 10 and 12 weeks, with most of the remainder prescribing a variable treatment duration. A minority of 14% gave only a single course of clindamycin and rifampicin, while the majority prescribed multiple courses depending on patient response. Ranking of the next most frequently chosen oral systemic treatments by mode was found to coincide with the frequency of being selected in respondents’ top 10 interventions (Fig. 1). Acitretin, isotretinoin, dapsone and ciclosporin were ranked third-, fourth-, fifthand sixth-choice interventions, respectively. Many respondents noted that use of biological agents was restricted by funding issues; however, 54 (46%) included infliximab in their top 10 treatments, 32 (27%) included adalimumab and 10 (9%) included ustekinumab. The two surgical treatment options listed in the survey were ‘narrow margin excision of most active lesion(s)’ and ‘wide local excision of most active region’. The limited excision option was offered by 38 (32%) respondents. Extensive excision was employed by 48 (41%) clinicians and the timing of this procedure in the treatment pathway varied from thirdto tenth-choice therapy, the mode being seventh choice. Three other interventions were included in their 10 mostused therapies by at least 20% of respondents, namely oral prednisolone (26%), intralesional triamcinolone injections (24%) and the oral contraceptive pill (21%). The group of laser, light, phototherapy and photodynamic therapies, comprising seven options in the treatment list, were infrequently used, selected only 16 times in total. Management of an acute flare was ranked as the second-highest priority in the HS Priority Setting Partnership. Survey respondents were asked to indicate their recommended management of an acute, painful HS abscess, and the results are shown in Fig. 2. The most frequent response was incision and drainage (43%). Prescription of a 1-week course of antibiotics was selected by 29%, although it has been suggested that this option may not alter the natural history of an individual HS lesion. This survey has provided insight into current U.K. management of HS, which broadly mirrors the recommendations of the European S1 guidelines, which were published after the survey closed. The results indicate that oral tetracyclines remain the first choice for systemic treatment in the U.K., while the combination of clindamycin and rifampicin is often, but not exclusively, prescribed as second-line therapy. Most clinicians prescribe 10–12-week combined courses of clindamycin 300 mg twice daily and rifampicin 300 mg twice daily, which is in line with published case series evidence, and the majority offer multiple courses. Isotretinoin continues to be used by about half of respondents, despite the available

Validation of the global resource of eczema trials (GREAT database).

Abstract: Background Eczema (syn. Atopic Eczema or Atopic Dermatitis) is a chronic, relapsing, itchy skin condition which probably results from a combination of genetic and environmental factors. The Global Resource of EczemA Trials (GREAT) is a collection of records of randomised controlled trials (RCTs) for eczema treatment produced from a highly sensitive search of six reference databases. We sought to assess the sensitivity of the GREAT database as a tool to save future researchers repeating extensive bibliographic searches.

Academic mentorship in dermatology

Abstract: The first reference to mentorship can be found in Greek mythology, when Odysseus asked the goddess Athena to nurture his son Telemachus. She achieved this disguised in human form as an old family friend by the name of Mentor. The Oxford English Dictionary defines a mentor as ‘a person who acts as guide and adviser to another person, especially one who is younger and less experienced.’ In essence, mentorship involves a trusting relationship in which a more experienced person uses their knowledge to guide someone less experienced. Mentorship is an important element of an evolving academic career, not least to minimize unintended consequences of a trainee’s actions in novel situations. Making mistakes can be a valuable but potentially painful method of learning, and not all mistakes can be undone. A mentor who has been in a similar position can provide empathetic advice to avoid mistakes and can provide an overview based on their greater experience.

Introducing cover image as a new category of publication in the BJD.

Abstract: The phrase ‘one picture is worth a thousand words’ became widely used in the U.S.A. in the early twentieth century. It has been attributed to Frederick R. Barnard in 1921, when commenting on the value of graphics in advertising in an American trade magazine. However, variants of the phrase appeared 100 years earlier, and the first use of the idiom is difficult to determine. The longevity of the phrase confirms its utility, and, in a visual specialty such as dermatology, there is rarely a better way to communicate information. Currently, in line with many other journals, the BJD displays one of the figures from each issue’s content as the cover image on the front page of the printed journal. Arguably, the cover image is one of the most important features of each issue, drawing readers into the journal. It is a prestigious and high-profile element of the publication. At the moment, the cover image is selected by the Editor, using a shortlist of figures identified by the editorial manager from articles appearing in the same issue. As a result, the same image features twice in each issue and the potential opportunity to impart new information is lost. A number of high-impact general medical journals have recognized the importance of clinical images and have developed a separate manuscript category, usually based on an educational case report format. Examples include Minerva in the BMJ, Clinical Pictures in the Lancet and Images in Clinical Medicine in the New England Journal of Medicine. The images are accompanied by text that adds educational value to the image and provides contextual information. They are a highly competitive element of these high-impact journals, particularly sought after by more junior authors as a chance to publish in a widely read communication. Having reflected on these issues, the BJD is introducing Cover Image as a new category of publication. It will be a stand-alone feature, accompanied by a concise scholarly caption of up to 100 words, which will be printed on the inside of the front cover. The photographs or images should be visually striking, high quality and, most importantly, of educational value. Examples of image types might include normal or diseased skin, an image using a diagnostic technique such as histopathology, immunostaining or electron microscopy, or a device. Historical images are also welcome, including treatments and historical milestones within dermatology. Submissions to the Cover Image section will undergo a rigorous selection process similar to any other BJD manuscript category. At least two members of the editorial team will provide an independent assessment, followed by a final decision from the Editor. Selection criteria will be scientific merit, visual impact, originality and relevance to the journal readership. It is intended that the Cover Image category will be particularly appealing to more junior authors, offering a chance for an accessible yet high-impact publication. In this context, at least one of the editorial selection team will be a BJD editorial registrar, at the end of their dermatology training, offering a ‘near-peer’ perspective. Creation of the new Cover Image category is consistent with the BJD’s aim to maximize the educational value of each journal component. The learning value of pictures is particularly useful for those readers in the ‘visual learning style’ group, whose retention of ideas and concepts is best facilitated by images. By providing a publication outlet for trainee dermatologists, the BJD will be supporting one of its key stakeholders, familiarizing trainees with the publication process. The restricted word count of the caption will reinforce the value of clarity and brevity in scholarly writing. Historical images will also provide trainees and others with a chance to reflect on the changing nature of dermatology practice over time. If the submitted picture is indeed worth a thousand words, authors should find it easy to explain and inform their submission with just 100 more.