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Background Chronic kidney disease (CKD) is common in aging men and women. In contrast to other European countries, Germany lacks CKD registries. The aim of this study was to determine the incidence of CKD stages 2–5 in men and women in Germany. Furthermore, differences between the sexes in terms of comorbidities, potentially inappropriate medications (PIM), and healthcare utilization were examined. Methods In this retrospective observational study, claims data from members of a statutory health insurance fund aged 18 years or older with incident CKD between 2011 and 2018 were analyzed. Incident CKD was defined as having two confirmed diagnoses of CKD stages 2–5 from outpatient care or one primary or secondary diagnosis from inpatient care. Results The age- and sex-standardized incidence of all CKD stages was 945/100 000 persons between 2011 and 2018. Incident CKD, especially stages 3 and 4, occurred more frequently in women, while the incidence of stages 2 and 5 was higher in men. While women visited their GP more frequently and were prescribed PIMs more often, men were more likely to visit a nephrologist and were more often hospitalized after the incident CKD diagnosis. Conclusion More awareness needs to be raised towards the early detection of CKD and the use of PIMs, especially in women. Improved care coordination is needed to avoid an overprovision of patients with uncomplicated incident stages and ensure that patients with advanced CKD stages get timely access to specialist care.

Purpose Preeclampsia occurs in up to 15% of pregnancies and constitutes a major risk factor for cardiovascular disease. This observational cohort study aimed to examine the association between preeclamptic pregnancies and cardiovascular outcomes as well as primary and specialized care utilization after delivery. Methods Using statutory claims data we identified women with singleton live births between 2010 and 2017. Main outcomes included the occurrence of either hypertension or cardiovascular disease after one or more preeclamptic pregnancies, number of contacts to a general practitioner or cardiologist after delivery and prescribed antihypertensive medication. Data were analyzed using Cox proportional hazard regression models adjusted for maternal age, diabetes, dyslipidemia, and obesity. Results The study cohort consisted of 181,574 women with 240,698 births. Women who experienced preeclampsia once had an increased risk for cardiovascular (hazard ratio, HR = 1.29) or hypertensive (HR = 4.13) events. In women affected by recurrent preeclampsia, risks were even higher to develop cardiovascular disease (HR = 1.53) or hypertension (HR = 6.01). In the following years after delivery, general practitioners were seen frequently, whereas cardiologists were consulted rarely (0.3 and 2.4%). Conclusion Women affected by preeclampsia experience an increased risk of developing chronic hypertension and cardiovascular disease, especially those with recurrent preeclampsia. Future medical guidelines should take this potential risk into account.

Dermatoses in pregnancy are common, they may be very itchy and may influence the life of a pregnant woman dramatically. There are four classical dermatoses of pregnancy, which this chapter will examine. It is particularly important to recognize these as they may have serious health implications for mother and child. Intrahepatic cholestasis of pregnancy occurs in 1/40 to 1/500 pregnancies and is the most serious cause of itch in pregnancy, with potentially substantial effects on mother and fetus. Meanwhile, atopic eruption of pregnancy affects 1/300 pregnancies, typically with an eczematous eruption over abdomen and limbs. Pemphigoid gestationis occurs in 1/50,000 pregnancies and is due to circulating antibodies against the skin basement membrane zone. The eruption often begins around the umbilicus and spreads to the whole trunk, limbs, hands, and feet. If potent topical steroids fail systemic steroids are required. Transplacental transmission to the fetus may also occur. Recurrence in future pregnancies is to be expected.

BACKGROUND: Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. METHODS: We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3-9, 10-30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (

Clinical trials may benefit clinical practice in three ways: firstly, clinicians may change their practice according to the new trial evidence; secondly, clinical processes can improve when working on a trial; and thirdly, research capacity is increased. We held a meeting to present and discuss the results of two large multicentre randomized controlled trials delivered through the U.K. Dermatology Clinical Trials Network. Investigators gave reflections on how the trials had changed their clinical practice. The STOP GAP trial showed that prednisolone and ciclosporin are equally effective as first-line systemic treatment for pyoderma gangrenosum. The final decision of which treatment to use should be based on the different adverse event profiles of the two drugs in relation to comorbidities, along with age, disease severity and patient preference. The BLISTER trial showed that starting people with pemphigoid on doxycycline produces acceptable short-term effectiveness and a superior safety profile to oral corticosteroids. Recruiting to these trials has led to the development of new specialist clinics with improved documentation. It has increased the profile of participating departments and embedded research in the department's activities. Helping to design and run these trials has also allowed trial staff to develop new skills in research design, which has been beneficial for career development. These and other benefits of recruiting to the trials are summarized here. We hope that these reflections will inspire wider involvement in clinical research.

BackgroundBullous pemphigoid (BP) is an autoimmune blistering skin disorder with increased morbidity and mortality in the elderly.ObjectivesTo evaluate the effectiveness, safety and cost-effectiveness of a strategy of initiating BP treatment with oral doxycycline or oral prednisolone. We hypothesised that starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral prednisolone.DesignPragmatic multicentre two-armed parallel-group randomised controlled trial with an economic evaluation.SettingA total of 54 dermatology secondary care centres in the UK and seven in Germany.ParticipantsAdults with BP [three or more blisters at two sites and positive direct and/or indirect immunofluorescence (immunoglobulin G and/or complement component 3 immunofluorescence at the dermal-epidermal junction)] and able to give informed consent.InterventionsParticipants were allocated using online randomisation to initial doxycycline treatment (200 mg/day) or prednisolone (0.5 mg/kg/day). Up to 30 g/week of potent topical corticosteroids was permitted for weeks 1–3. After 6 weeks, clinicians could switch treatments or alter the prednisolone dose as per normal practice.Main outcome measuresPrimary outcomes: (1) the proportion of participants with three or fewer blisters at 6 weeks (investigator blinded) and (2) the proportion with severe, life-threatening and fatal treatment-related events at 52 weeks. A regression model was used in the analysis adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Secondary outcomes included the effectiveness of blister control after 6 weeks, relapses, related adverse events and quality of life. The economic evaluation involved bivariate regression of costs and quality-adjusted life-years (QALYs) from a NHS perspective.ResultsIn total, 132 patients were randomised to doxycycline and 121 to prednisolone. The mean patient age was 77.7 years and baseline severity was as follows: mild 31.6% (three to nine blisters), moderate 39.1% (10–30 blisters) and severe 29.3% (> 30 blisters). For those starting on doxycycline, 83 out of 112 (74.1%) had three or fewer blisters at 6 weeks, whereas for those starting on prednisolone 92 out of 101 (91.1%) had three or fewer blisters at 6 weeks, an adjusted difference of 18.6% in favour of prednisolone [90% confidence interval (CI) 11.1% to 26.1%], using a modified intention-to-treat (mITT) analysis. Per-protocol analysis showed similar results: 74.4% compared with 92.3%, an adjusted difference of 18.7% (90% CI 9.8% to 27.6%). The rate of related severe, life-threatening and fatal events at 52 weeks was 18.2% for those started on doxycycline and 36.6% for those started on prednisolone (mITT analysis), an adjusted difference of 19.0% (95% CI 7.9% to 30.1%;p = 0.001) in favour of doxycycline. Secondary outcomes showed consistent findings. There was no significant difference in costs or QALYs per patient at 1 year between doxycycline-initiated therapy and prednisolone-initiated therapy (incremental cost of doxycycline-initiated therapy £959, 95% CI –£24 to £1941; incremental QALYs of doxycycline-initiated therapy –0.024, 95% CI –0.088 to 0.041). Using a willingness-to-pay criterion of ConclusionsA strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and considerably safer in the long term. The limitations of the trial were the wide non-inferiority margin, the moderate dropout rate and that serious adverse event collection was unblinded. Future work might include inducing remission with topical or oral corticosteroids and then randomising to doxycycline or prednisolone for maintenance.Trial registrationCurrent Controlled Trials ISRCTN13704604.FundingThis 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. 21, No. 10. See the NIHR Journals Library website for further project information.

The objective of this study was to investigate whether circulating basement membrane zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy-confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1-4). Immunoblotting was carried out on salt-split and urea-extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal-binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.

The aim of the study was to investigate the prevalence of hepatitis C (HCV) antibodies, hepatitis B surface antigen (HBsAg) carriage and liver disease in 100 females with genital lichen planus (LP) in Oxfordshire. Sera were screened for HCV antibodies (AxSYM HCV 3.0 Abbott), HBV surface antigen (AxSYM HBsAg V2 Abbott), mitochrondrial and anti-smooth muscle antibodies. Liver function tests were undertaken. All sera were negative for HCV antibody and HBsAg. Transiently abnormal liver function tests (2) and liver specific antibodies (2) were detected in four patients with no underlying liver disease. We found no association between HBV or HCV and genital LP in this population.

Clinical Question Are topical corticosteroids safe for use in pregnancy? Bottom Line The available evidence found no associations of maternal use of topical corticosteroids of any potency with mode of delivery, birth defects, preterm delivery, fetal death, and low Apgar score. However, maternal use of potent to very potent topical corticosteroids, especially when the cumulative dosage of topical corticosteroids throughout the pregnancy is very large, is associated with low birth weight.

Background Lichen sclerosus is a chronic inflammatory skin disease. It is thought to be underdiagnosed and undertreated. If it is not treated, lichen sclerosus is associated with a greater degree of scarring and an elevated risk of cancer in the genital area.

Background Pregnant women may have skin conditions that require topical corticosteroids. However, little is known about their safety in pregnancy. Objective We sought to evaluate the available evidence concerning the safety of topical corticosteroids in pregnancy. Methods We systematically searched 17 databases and trial registers, and contacted pharmaceutical companies. Randomized controlled trials and cohort studies of topical corticosteroids in pregnant women, and case-control studies comparing maternal exposure to topical corticosteroids between patients and control subjects were included. The Newcastle-Ottawa Scale was used for quality assessment of included studies. Results Seven studies, including two cohort and five case-control studies, were included. Most studies did not find significant associations of topical corticosteroids with congenital abnormality, preterm delivery stillbirth, and mode of delivery. One study found a significant association between first-trimester use of topical corticosteroids and orofacial cleft, and another study found a significant association between very potent topical corticosteroids and low birthweight. Limitations The available data were limited and mainly on orofacial cleft. The quality of evidence was generally low. Conclusions Currently limited and inconclusive data are unable to detect an association between topical corticosteroids and congenital abnormality, preterm delivery, or stillbirth. The current evidence shows no statistically significant difference between pregnant women who use and those who do not use topical corticosteroids. However, there does appear to be an association of very potent topical corticosteroids with low birthweight. Further cohort studies with comprehensive outcome measures, consideration of corticosteroid potency, dosage and indications, and a large sample size are needed.

Background Systemic glucocorticoids (GCs) are often needed to treat dermatologic patients. The long-term use of GCs, however, is associated with potentially severe side-effects. GC-induced osteoporosis (GIO) is one of the most serious complications, but the risk of the occurrence of GIO seems to be generally underestimated. Aim To provide an update of the recent advances in the prevention of GIO in dermatologic practice. Methods Review of the literature and several European and US guidelines up to August 2007. Results Data regarding the prevention and treatment of GIO are limited and guidelines for the prevention of GIO are not fully consistent. Conclusion The prophylaxis of osteoporosis needs to be started early during treatment with GCs. Calcium and vitamin D supplements in all patients on systemic GCs and bisphosphonates in patients who take GCs for more than 3 months are practical and effective measures.

Summary Background Chronic wounds represent a major problem to our society. Therefore, advanced wound-healing strategies for the treatment of these wounds are expanding into the field of tissue engineering. Objectives To develop a novel tissue-engineered, autologous, full-thickness skin substitute of entirely human origin and to determine its ability to heal chronic wounds. Methods Skin substitutes (fully differentiated epidermis on fibroblast-populated human dermis) were constructed from 3-mm punch biopsies isolated from patients to be treated. Acellular allodermis was used as a dermal matrix. After a prior 5-day vacuum-assisted closure therapy to prepare the wound bed, skin substitutes were applied in a simple one-step surgical procedure to 19 long-standing recalcitrant leg ulcers (14 patients; ulcer duration 0·5–50 years). Results The success rate in culturing biopsies was 97%. The skin substitute visibly resembled an autograft. Eleven of the 19 ulcers (size 1–10 cm2) healed within 8 weeks after a single application of the skin substitute. The other eight larger (60–150 cm2) and/or complicated ulcers healed completely (n = 5) or continued to decrease substantially in size (n = 3) after the 8-week follow-up period. Wound healing occurred by direct take of the skin substitute (n = 12) and/or stimulation of granulation tissue/epithelialization (n = 7). Skin substitutes were very well tolerated and pain relief was immediate after application. Conclusions Application of this novel skin substitute provides a promising new therapy for healing chronic wounds resistant to conventional therapies.

In 1953, Lever differentiated bullous pemphigoid from autoimmune pemphigus. The natural course of bullous pemphigoid is relatively benign, with a disease-related mortality rate of 24% compared with around 70% in pemphigus. In spite of the introduction of systemic corticosteroids, the mortality rates in bullous pemphigoid have generally not improved and vary between 0% and 40%. Higher doses of systemic corticosteroids seem to be associated with higher mortality rates, which led to the addition of corticosteroid-sparing agents to the treatment of bullous pemphigoid. However, many of these modalities are also accompanied by severe adverse effects and have not led to a significant decrease in the mortality rate. In recent years, there has been a move toward less toxic treatment options for a disease that is usually self-limited. A systematic review of the literature found that treatment with lower doses of systemic corticosteroids and potent topical corticosteroids is effective and accompanied by less serious adverse effects, including death. No benefit of the addition of plasmapheresis or azathioprine to systemic corticosteroids has been shown. The treatment of bullous pemphigoid with tetracyclines and niacinamide (nicotinamide) is effective and accompanied by less serious adverse effects. However, more randomized controlled trials are needed to confirm these results and to determine the best treatment for bullous pemphigoid.

Twenty patients with bullous pemphigoid were studied prospectively: sequential sera, in different phases of the disease, were collected over a period of approximately 2 years, the sera were tested using standard immunofluorescence techniques with salt-split and intact human tissue from different sites of the body (thigh, breast, oral mucosa, vagina); an early serum of each patient was tested by Western blotting. The concentration of circulating antibodies detected by the intact skin and intact mucous membranes was similar; split tissue was more sensitive than intact tissue. For eight of 19 patients, split vagina and occasionally split oral mucosa (in the same patients) were much less sensitive than all other tissues. Furthermore, there was a correlation between autoantibody reactivity with split mucous membrane tissues and clinical mucosal involvement. These results strongly suggest heterogeneity of antigens or epitopes expressed between tissues. In both split skin and mucosa all sera consistently detected an antigen on the epidermal side of the split regardless of the stage of the disease. Immunoblotting studies showed no correlation between specific antigens and mucosal expression or skin involvement.

Das vernarbende Pemphigoid (VP) umfast eine Gruppe von Patienten mit einer chronischen, subepidermal blasenbildenden Dermatose, welche primar die Schleimhaute betrifft; die Lasionen heilen charakteristischerweise unter Narbenbildung. Immunfluoreszenzuntersuchungen weisen lineare Ablagerungen von IgG und weniger oft von IgA entlang der Basalmembranzone nach. Diesen Autoantikorpern wird eine entscheidende Rolle bei der Pathogenese der Blasenbildung zugestanden. Der groste Teil der Patienten mit VP bindet das 180 kD schwere bullose Pemphigoidantigen 2 (BPag2), Kollagen Typ XVII. Eine kleine Gruppe weist Autoantikorper gegen Laminin 5 auf. Die pathogenetische Relevanz der Autoantikorperbindung an diese Adhasionsmolekule (BPag2 und Laminin 5) konnte im Tiermodell bestatigt werden. Desweiteren werden bei kleineren Gruppen oder bei einzelnen Patienten mit VP Autoantikorper gegen meist nicht naher charakterisierte Antigene beschrieben. Die besprochenen Molekule bilden den hemidesmosomalen Adhasionskomplex. Es ist nachvollziehbar, das bei gestorter Funktion einer der Komponenten die Separation der Epidermis von der Dermis resultiert; bessere Kenntnisse uber die einzelnen Molekule und die genaue Antikorperbindungsstelle konnten Ruckschlusse auf das klinische Bild zulassen.

We have recently identified patients with a form of cicatricial pemphigoid who have IgG anti-basement membrane autoantibodies directed against epiligrin, a laminin isoform closely related if not identical to laminin 5. These patients' autoantibodies bind the lower lamina lucida of human epidermal basement membrane and immunoprecipitate this laminin isoform from extracts and media of biosynthetically radiolabeled human keratinocytes. Immunoblot studies show that these patients' autoantibodies specifically bind the alpha subunit of this laminin (i.e., laminin subunit alpha 3). We have found no evidence of these autoantibodies in normal volunteers or patients with other bullous skin diseases (including those with other forms of CP). These studies have identified a group of patients with an acquired, autoimmune, subepidermal bullous disorder who have disease-specific autoantibodies directed against the alpha subunit of epiligrin/laminin 5. These findings correlate with prior reports showing that a monoclonal antibody directed against this laminin subunit induces detachment of keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these findings suggest that this laminin mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic. Moreover, recent studies showing that subunits of this laminin isoform are mutated in some patients with Herlitz's junctional epidermolysis bullosa indicate that acquired or inherited abnormalities in this adhesion ligand are associated with skin diseases characterized by separation of epidermis from epidermal BM.

Erosive lichen planus (ELP) affecting mucosal surfaces is a chronic autoimmune disease of unknown aetiology. It is often more painful and debilitating than the non-erosive types of lichen planus. Treatment is difficult and aimed at palliation rather than cure. Several topical and systemic agents have been used with varying results.To assess the effects of interventions in the treatment of erosive lichen planus affecting the oral, anogenital, and oesophageal regions.We searched the following databases up to September 2009: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched reference lists of articles and online trials registries for ongoing trials.We considered all randomised controlled trials (RCTs) that evaluated the effectiveness of any topical or systemic interventions for ELP affecting either the mouth, genital region, or both areas, in participants of any age, gender, or race.The primary outcome measures were as follows:(a) Pain reduction using a visual analogue scale rated by participants; (b) Physician Global Assessment; and (c) Participant global self-assessment.Changes in scores at the end of therapy compared with baseline were analysed.A total of 15 RCTs were identified, giving a total of 473 participants with ELP. All studies involved oral ELP only. Six of the 15 studies included participants with non-erosive lichen planus. In these studies, only the erosive subgroup was included for intended subgroup analysis. We were unable to pool data from any of the nine studies with only ELP participants or any of the six studies with the ELP subgroup, due to small numbers and the heterogeneity of the interventions, design methods, and outcome variables between studies. One small study involving 50 participants found that 0.025% clobetasol propionate administered as liquid microspheres significantly reduced pain compared to ointment (Mean difference (MD) -18.30, 95% confidence interval (CI) -28.57 to -8.03), but outcome data was only available in 45 participants. However, in another study, a significant difference in pain was seen in the small subgroup of 11 ELP participants, favouring ciclosporin solution over 0.1% triamcinolone acetonide in orabase (MD -1.40, 95% CI -1.86 to -0.94). Aloe vera gel was 6 times more likely to result in at least a 50% improvement in pain symptoms compared to placebo in a study involving 45 ELP participants (Risk ratio (RR) 6.16, 95% CI 2.35 to 16.13). In a study involving 20 ELP participants, 1% pimecrolimus cream was 7 times more likely to result in a strong improvement as rated by the Physician Global Assessment when compared to vehicle cream (RR 7.00, 95% CI 1.04 to 46.95).There is no overwhelming evidence for the efficacy of a single treatment, including topical steroids, which are the widely accepted first-line therapy for ELP. Several side-effects were reported, but none were serious. With topical corticosteroids, the main side-effects were oral candidiasis and dyspepsia.This review suggests that there is only weak evidence for the effectiveness of any of the treatments for oral ELP, whilst no evidence was found for genital ELP. More RCTs on a larger scale are needed in the oral and genital ELP populations. We suggest that future studies should have standardised outcome variables that are clinically important to affected individuals. We recommend the measurement of a clinical severity score and a participant-rated symptom score using agreed and validated severity scoring tools. We also recommend the development of a validated combined severity scoring tool for both oral and genital populations.

Background Lichen sclerosus (LS) is a chronic inflammatory dermatosis that occurs mainly in the anogenital area and causes itching and soreness. Progressive destructive scarring may result in burying of the clitoris in females and phimosis in males. Affected people have an increased risk of genital cancers. Objective We sought to assess the effects of topical interventions for genital LS. Methods We undertook a systematic review and meta-analysis using the methodology of the Cochrane Collaboration. Results We included 7 randomized controlled trials with a total of 249 participants covering 6 treatments. Clobetasol propionate 0.05% was better than placebo in treating genital LS (participant-rated improvement/remission of symptoms: risk ratio 2.85 [95% confidence interval {CI} 1.45-5.61]; investigator-rated global degree of improvement: standardized mean difference [SMD] 5.74 [95% CI 4.26-7.23]) as was mometasone furoate 0.05% (change in clinical grade of phimosis: SMD −1.04 [95% CI −1.77 to −0.31]). We found no evidence supporting the efficacy of topical androgens and progesterone. There were no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (SMD −0.33 [95% CI −0.99 to 0.33]) and burning/pain (SMD 0.03 [95% CI −0.62 to 0.69]). However, pimecrolimus was less effective than clobetasol propionate in improving gross appearance (investigator-rated global degree of improvement: SMD −1.64 [95% CI −2.40 to −0.87]). Limitations Most of the included studies were small. Conclusions The current limited evidence supports the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital LS. Further randomized controlled trials are needed.

Background The Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) tool is intended to be used in the design phase of trials to help investigative teams design trials in-line with their purpose. Our team applied this tool to an ongoing trial (BLISTER) to determine whether the initial suggestion among some team members that the trial could be described as largely pragmatic was the consensus. Methods Each of the six members of the BLISTER trial team was sent a blank PRECIS wheel to independently complete. The results obtained were averaged and plotted on a single PRECIS wheel to illustrate the degree of pragmatism of the trial. Results The trial team found that the design of the trial was closest to the pragmatic end of the pragmatic-explanatory continuum. The strongest consensus was found on the ‘flexibility of the comparison intervention’ and ‘practitioner adherence’ domains (SD = 13). The trial team appeared to disagree most on the ‘eligibility criteria’ (SD = 35) and ‘participant compliance’ (SD = 31) domains, although the large standard deviations were a result of a single outlier in the two domains. Conclusion The PRECIS tool can be used to retrospectively determine the pragmatism of a trial provided enough expertise and information on the trial is available. Illustrating the design of a trial on the PRECIS wheel can help research users more easily identify studies of interest. We hope our recommendations for applying this useful tool will encourage others to consider using it when designing, conducting and reporting studies. Trial registration Current Controlled Trials http://www.controlled-trials.com/ISRCTN13704604

BACKGROUND: Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily affects the genital area and around the anus, where it causes persistent itching and soreness. Scarring after inflammation may lead to severe damage by fusion of the vulval lips (labia); narrowing of the vaginal opening; and burying of the clitoris in women and girls, as well as tightening of the foreskin in men and boys, if treatments are not started early. Affected people have an increased risk of genital cancers. OBJECTIVES: To assess the effects of topical interventions for genital lichen sclerosus and adverse effects reported in included trials. SEARCH METHODS: We searched the following databases up to 16 September 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British Nursing Index and Archive (from 1985), Science Citation Index Expanded (from 1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and Conference Proceedings Citation Index ‐ Science (from 1990). We also searched ongoing trial registries and scanned the bibliographies of included studies, published reviews, and papers that had cited the included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of topical interventions in genital lichen sclerosus. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion. MAIN RESULTS: We included 7 RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs tested the efficacy of one active intervention against placebo or another active intervention, while the other trial tested three active interventions against placebo. When compared to placebo in one trial, clobetasol propionate 0.05% was effective in treating genital lichen sclerosus in relation to the following outcomes: 'participant‐rated improvement or remission of symptoms' (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator‐rated global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI 4.26 to 7.23). When mometasone furoate 0.05% was compared to placebo in another trial, there was a significant improvement in the 'investigator‐rated change in clinical grade of phimosis' (SMD ‐1.04, 95% CI ‐1.77 to ‐0.31). Both trials found no significant differences in reported adverse drug reactions between the corticosteroid and placebo groups. The data from four trials found no significant benefit for topical testosterone, dihydrotestosterone, and progesterone. When used as maintenance therapy after an initial treatment with topical clobetasol propionate in another trial, topical testosterone worsened the symptoms (P < 0.05), but the placebo did not. One trial found no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (itching) (SMD ‐0.33, 95% CI ‐0.99 to 0.33) and burning/pain (SMD 0.03, 95% CI ‐0.62 to 0.69). However, pimecrolimus was less effective than clobetasol propionate with regard to the 'investigator‐rated global degree of improvement' (SMD ‐1.64, 95% CI ‐2.40 to ‐0.87). This trial found no significant differences in reported adverse drug reactions between the pimecrolimus and placebo groups. AUTHORS' CONCLUSIONS: The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.