Systematic review of combination therapies for mycosis fungoides.

BACKGROUND: A variety of therapeutic options are available for mycosis fungoides, the most prevalent subtype of cutaneous T cell lymphomas, but thus far, no regimen has been proven to be curative. A combination of treatments is a well-established strategy to increase the therapeutic efficacy. However, data from clinical trials analyzing such combinations for the treatment of mycosis fungoides are scarce. OBJECTIVE: To analyze the available evidence on combination therapies with emphasis on the combination of psoralen with UVA phototherapy (PUVA), interferon-alpha and bexarotene with another treatment. METHODS: Systematic literature review of the databases Embase, Cochrane, Medline, and Medline in Process. RESULTS: Combination of PUVA with interferon-alpha or retinoids did not result in an increased overall response rate. Addition of methotrexate but not retinoids to interferon-alpha may increase the overall response rate. Bexarotene was investigated in one trial each with vorinostat, methotrexate or gemcitabine, whereby only methotrexate possibly enhanced the effect of bexarotene. CONCLUSION: For mycosis fungoides, no combination treatment has been demonstrated to be superior to monotherapy. Based on our analysis, we conclude that in certain clinical situations, patients may benefit from a combination of PUVA with interferon-alpha or a retinoid or a combination of the latter two. Furthermore, patients in advanced stages may benefit from the combination of methotrexate and interferon-alpha or bexarotene. Finally, the combination of bexarotene with either vorinostat or gemcitabine did not increase the overall response rate but resulted in more pronounced side effects and cannot be recommended.

Study of perceptions of the extent to which guideline recommendations are binding: a survey of commonly used terminology.

BACKGROUND: Doctors are more likely to implement guidelines in their everyday practice if the recommendations contained in them are understandable. So far, there has been little standardization in the wording of guideline recommendations. It would be important to know how certain terms are understood by guideline users. In this study, doctors were asked in a survey about what they considered to be the level of obligation carried by various formulations that are commonly used in guidelines to recommend particular courses of action. METHODS: An online survey of physicians (mostly dermatologists) was carried out in which they were asked to rate, on a visual analog scale, what they perceived to be the level of obligation of various common formulations for guideline recommendations. RESULTS: The terms "muss" (must) and "darf nicht" (must not) were interpreted as being maximally binding. The two closely related German words "soll" (shall) and "sollte" (should) were considered highly binding, as were negative formulations such as "wird nicht empfohlen" (is not recommended). The perceived level of obligation of "soll" did not differ from that of "sollte" to any detectable extent, nor was there any detectable distinction between the various negative formulations studied. Formulations with the words "wird empfohlen" (is recommended), "kann empfohlen werden" (can be recommended), or other "kann" (can) expressions were considered to be only mildly or moderately binding. In general, there was marked variation in the perceived level of obligation of formulations located in the low and middle ranges. CONCLUSION: These findings suggest that guideline users do not necessarily perceive recommendation strengths as the guideline authors intended. It might be better if positive recommendations came in only two different strengths, while a single recommendation strength might suffice for negative ones. Further studies should shed more light on this question.

Can physician's self-estimates be used as a valid instrument to determine prescription frequencies of anti-psoriatic drugs? Comparison of the results of a cross-sectional study using self-estimates with actual prescription behavior documented in a cohort study.

PURPOSE: Physicians' self-estimates of their own prescription behavior can be used as a tool to gather information on prescription frequencies. Self-estimates as a tool for health-care research on prescription frequencies need to be validated as a suitable method before it can be used widely. METHODS: We performed a cross-sectional study inviting all dermatologists in Berlin and Brandenburg to give self-estimates of their own prescription behavior of anti-psoriatic drugs. The results were compared with the results from a consecutive 8-months cohort study with the same participants documenting their actual treatment choices during every visit of a psoriasis patient on a standardized documentation sheet. Differences between self-estimates and documented prescription patterns were analyzed with respect to systemic anti-psoriatic drugs and UV treatment. RESULTS: Fifty-one dermatologists participated. They documented an average of 91 patient visits each. Absolute differences between the self-estimates and the documented actual prescription behavior ranged from -2.5% to 1.4% for systemic treatments. For psoralen plus ultravioloet A (PUVA) treatment, the absolute difference was 3.3% and for ultraviolet B (UVB) 4.7%. CONCLUSIONS: Self-estimates were surprisingly exact. Self-estimates may be suggested as one tool to assess prescription frequencies, but further studies are needed to confirm their validity.

Management of anticoagulation during dermatosurgical procedures in Germany - results from a cross-sectional study.

BACKGROUND: Treatment with antiplatelet drugs (APD) and vitamin K antagonists (VKA) can be a challenge during the management of dermatosurgical interventions. METHODS: We performed a cross-sectional study on the perioperative management of APD and VKA in dermatological private practices and clinics in Germany, using anonymized, standardized questionnaires. RESULTS: 233 responses were evaluated (response rate 37 %). Skin biopsies are performed in 82.7 % of offices and in 90.8 % of clinics despite treatment with VKA. Small excisions are done in 62.5 % of offices and 76.9 % of clinics during treatment with VKA, for large excision this applies to 11.9 % of offices and 33.8 % of clinics. Low-dose treatment with APD (#100 mg) does not hinder 80.4 % of private practices and 89.2 % of clinics to perform small excisions as well as 36.3 % and 53.8 %, respectively, to perform large excisions. Of private practitioners 67.3 % and 83.1 % of clinic-based dermato-surgeons do not consider high-dose APD a contraindication for small excisions, and 25.0 % and 41.5 %, respectively, for large excisions. Most frequently switching to heparin is performed 6-8 days prior to surgery and switching back 0-2 days after surgery. CONCLUSIONS: Large differences in the perioperative management of anticoagulant therapy during dermatosurgical procedures have been identified. Further studies and guidelines should be developed.

S3 - Guidelines on the treatment of psoriasis vulgaris (English version). Update.

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5% to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, surveys have shown that patients still do not received optimal treatments. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologi sche Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. They were first published in 2006 and updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate and severe plaque-type psoriasis in adults including systemic therapy, UV therapy and topical therapies. The therapeutic recommendations were developed based on the results of a systematic literature search and were finalized during a consensus meeting using structured consensus methods (nominal group process).

[S3-guidelines for the treatment of psoriasis vulgaris--methods report]. / S3-Leitlinie zur Therapie der Psoriasis vulgaris--Methodenreport.

BACKGROUND: This methods report summarizes the methodology used to update the German Psoriasis Guidelines. METHODS: The guidelines were developed following the recommendations of the Association of the Scientific Medical Societies in Germany. Medline, Cochrane Library and Embase were searched to generate new evidence. In addition, the results from the literature search from the EU Psoriasis Guidelines were used. The recommendations were discussed during a consensus conference using nominal group technique and were voted on during the Delphi procedure. An extensive internal and external review (open) was performed. RESULTS: Due to changes in drug licensing efalizumab was excluded from the guidelines and adalimumab and ustekinumab were added. 97 new studies were included to serve as a basis for the recommendations. The level of evidence improved for calcineurin inhibitors from level 4 to level 2/3 and for MTX and systemic retinoids from level 3 to level 2. A lack of evidence still exists for coal tar (level of evidence 4). All other described interventions have a level of evidence of 2 or 1. CONCLUSIONS: The field of psoriasis therapy is in constant transition. A lack of head to head trials makes direct comparisons still a challenging task. Continuous updating will be necessary to respond to the further changes expected in the field of psoriasis.

Efficacy and durability of two hyaluronic acid-based fillers in the correction of nasolabial folds: results of a prospective, randomized, double-blind, actively controlled clinical pilot study.

BACKGROUND: This pilot study compared a monophasic hyaluronic acid dermal filler with a biphasic filler for the correction of nasolabial folds. METHODS: Participant- and assessor-blinded, randomized clinical trial involving participants with moderate to severe nasolabial folds. Split-face design comparing a monophase hyaluronic acid (HA) filler (mono-HA) with a biphasic HA filler (bi-HA). Injection with touch-up after 1 month. Wrinkle improvement was measured before and after injection and after 1, 2, 4, and 7 months, using the Wrinkle Severity Rating Scale and the Global Aesthetic Improvement Scale as outcome criteria. An optional treatment was offered at the end of the study, with participants allowed to choose one of the products. OBJECTIVE: Evaluation of efficacy and safety of both products. RESULTS: Both products showed immediate, good results after injection and touch-up and demonstrated good durability over time. Participant preference for optional treatment at the end of the study favoured mono-HA. Both products were well tolerated, without serious adverse events. CONCLUSION: The effect after injection of mono-HA and bi-HA is generally comparable, although there was a trend in favor of mono-HA. Materials and funding for this study were provided by Teoxane, Geneva, Switzerland.

The current state of treatment of adverse reactions to injectable fillers.

BACKGROUND: Adverse reactions to injectable filler may be challenging to treat. The spectrum of treatment options ranges from immunomodulatory drugs (e.g., glucocorticosteroids) to antibiotics to laser therapy and surgery. OBJECTIVES: To assess how adverse reactions were treated and how they processed over time. MATERIALS AND METHODS: Participants from the Injectable Filler Safety (IFS) Study were reinterviewed to obtain data on the course of adverse reactions and the therapy. RESULTS: Forty-one participants from the IFS Study were reinterviewed; 35 (85%) received treatment, 17 (41%) with a combination of drug therapy and surgery, 14 (34%) with drug therapy only, and four (10%) with a surgical intervention. Six (15%) did not receive any treatment. Fifty-one percent of all of the treated participants reported treatment-related adverse reactions. Participants with more severe adverse reactions were more likely to be treated with a combination of drugs and surgery. In all participants, adverse reactions improved. CONCLUSION: We certainly need more evidence. Reporting positive and negative treatment outcomes is important to improve our knowledge regarding these reactions. Therefore, registries focusing on adverse reactions to injectable fillers and their treatment should be encouraged. The authors have indicated no significant interest with commercial supporters.

[S2k-guideline for therapy of acne]. / S2k-leitlinie zur therapie der akne.

To optimize the treatment of acne in Germany, the German Society of Dermatology (DDG) and the Association of German Dermatologists (BVDD) initiated a project to develop consensus-based guidelines for the management of acne. The Acne Guidelines focus on induction therapy, maintenance therapy and treatment of post-acne scarring. They include an evaluation of the most commonly used therapeutic options in Germany. In addition, they offer detailed information on how to administer the various treatments and on contraindications, adverse drug reactions, and drug interactions, taking into account gender and special conditions such as pregnancy and lactation. The Acne Guidelines were developed following the recommendations of the Association of Scientific Medical Societies in Germany (AWMF). The treatment recommendations were developed by an expert group and finalized by an interdisciplinary consensus conference. The first choice treatments for acute acne according to acne type are as follows: 1) comedonal acne: topical retinoids; 2) mild papular/pustular acne: fixed or sequential combinations of BPO and topical retinoids or of BPO and topical antibiotics; 3) moderate papular/pustular acne: oral antibiotic plus BPO or plus topical retinoid, or in a fixed combination 4) acne papulo-pustulosa nodosa and acne conglobata: oral antibiotic plus topical retinoid plus BPO or oral isotretinoin. For maintenance treatment: topical retinoid or its combination with BPO. Particular attention should be paid to compliance and quality of life. Additional treatment options are discussed in the main body of the text.

Hyaluronidase in the correction of hyaluronic acid-based fillers: a review and a recommendation for use.

BACKGROUND: Hyaluronic acid (HA) preparations are the most commonly used injectable fillers in esthetic medicine. In contrast to other injectable fillers with hyaluronidase, there is a tool available to reduce unwanted depots of this filler. AIMS: The aim of this paper is to give an overview on the present literature and in addition to give some recommendations for use based on the experience of the authors. METHODS: The overview is based on a literature search. RESULTS: There is some evidence from two smaller clinical trials that hyaluronidase will effectively decrease injected depots of HA. It has further been shown from case series and case reports that this reduction is clinically relevant. There is less evidence that hyaluronidase is also helpful in adverse reactions to HA-based fillers. CONCLUSIONS: The reports suggest that the treatment is safe. However, adverse reactions to hyaluronidase such as allergic reactions have been reported. Patient should be informed about that before treatment.

The spectrum of adverse reactions after treatment with injectable fillers in the glabellar region: results from the Injectable Filler Safety Study.

BACKGROUND: For the glabellar region, severe partly vascular adverse events have been reported after treatment with injectable fillers. METHODS AND MATERIALS: For this study, data from the Injectable Filler Safety Study, a German-based registry for those reactions, was analyzed to characterize adverse events seen in the glabellar region. Patients were analyzed descriptively. RESULTS: Forty of 139 registered patients reported adverse events in the glabellar region. All patients were female, with an average age of 52.3. Nineteen patients with adverse reactions to hydroxyethylmethacrylate (HEMA) and ethylmethacrylate (EMA) in a fixed combination with hyaluronic acid (HA) and 10 patients with adverse reactions to different hyaluronic acid products were reported; five patients reacted to poly-L-lactic acid (PLA). The most common adverse reactions to HEMA/EMA in HA and PLA were nodules and hardening. In HA-treated patients, erythema and inflammation, swelling, and pain were most frequent. The adverse reactions to HEMA/EMA in HA were severe in 50% of the patients. Severe adverse reactions were found to a lesser extent in patients treated with HA and PLA. Potential vascular complications were documented in only two patients. CONCLUSION: Adverse reactions seen in the glabella are overwhelmingly product associated and to a lesser extent location associated. Vascular complications with necrosis and ulceration were rare.

Decrease of reported adverse events to injectable polylactic acid after recommending an increased dilution: 8-year results from the Injectable Filler Safety study.

BACKGROUND: Injectable fillers are widely used in aesthetic medicine. Polylactic acid (PLA) is a semipermanent filler that needs to be diluted with sterile water before injection. PLA has been associated with an increased risk of adverse reactions, specifically nodule formation. OBJECTIVE: To describe adverse reactions to PLA and potential risk factors based on a partly population-based registry over an 8-year period. METHODS: The Berlin registry is a partially population-based registry where dermatologists, plastic surgeons, and other specialists are contacted regularly and asked to report patients with adverse events to injectable fillers substances. Additional patients were derived from private practices outside of Berlin. The patients were assessed with a standardized questionnaire. The results were mainly analyzed by descriptive measures. RESULTS: Twenty-two patients (age, 47.82 +/- 12.65 years) with adverse reactions to PLA were included. The most frequent adverse reaction was nodule formation found in all patients. In 13 (59.1%) of the cases, nodule formation was considered to be severe. Nodules appeared after a mean latency period of 6.00 +/- 5.84 months. The duration of the adverse reactions until the interview was 14.32 +/- 10.13 months. The frequency of patients with adverse events to PLA was found to decrease after new recommendations concerning the dilution of the product were launched. CONCLUSION: PLA is an injectable filler substance that may cause subcutaneous nodules in treated patients. Our data support a decreased risk of adverse reactions with an increased dilution. However, nodule formation still appears to be a characteristic feature of PLA.

Translating psoriasis treatment guidelines into clinical practice - the need for educational interventions and strategies for broad dissemination.

RATIONALE: Evidence-based guidelines can make a substantial contribution to improving medical care. However, it is important to ensure that guidelines are: (1) developed in areas in which they are needed the most; and (2) translated effectively into everyday clinical practice. OBJECTIVES: To evaluate the need for guidelines in the treatment of psoriasis vulgaris, the success of the dissemination activities undertaken to date, and the potential benefits of educational interventions in encouraging guideline compliance. METHODS: All dermatologists working in the Berlin-Brandenburg region of Germany were invited to attend a workshop on the psoriasis treatment guidelines. Participants could take part in a survey examining the general need for psoriasis guidelines and the success of previous dissemination activities. RESULTS: A total of 42% of survey participants had not received a copy of the guidelines prior to the workshop. Of those who had received a copy, only 15% had studied the guidelines in detail. In total, 76% of survey participants felt that physicians' low levels of confidence in administering systemic treatments had resulted in these treatment options being used less frequently than they should. Seventy-nine per cent of survey participants believed that the guidelines would be helpful in improving physicians' confidence and ultimately lead to an increased use of systemic treatments. CONCLUSION: The results of the present study indicate that there is a great need for guidelines on the treatment of psoriasis vulgaris in Germany, especially in light of dermatologists' low levels of confidence administering systemic treatments. Strategies for broad dissemination are essential for proper guideline implementation.

[Continuing medical education in aesthetic medicine: hands-on course with anatomic preparations for hand augmentation with injectable hyaluronic acids]. / Fortbildung Asthetische Medizin: Hospitationskurs am anatomischen Präparat zur Augmentation des Handrückens mit injizierbaren Hyaluronsäurepräparaten.

The Division of Evidence Based Medicine (dEBM), part of the Clinic for Dermatology, Venerology and Allergology, Charité - University Hospital Berlin, offers on a regular basis workshops focusing on different areas of aesthetic medicine. This year in cooperation with the Institute of Anatomy a joint course was designed and conducted. The course focused on the treatment with hyaluronic acids of different particle size for a new indication, hand augmentation. Fourteen physicians participated in this course. The evaluation of the course ranged between very good and good.