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Zusammenfassung Hintergrund Die aktinische Keratose (AK) ist ein epitheliales Carcinoma in situ der Haut. Aufgrund des Risikos einer malignen Transformation besteht ein frühzeitiger Behandlungsbedarf. Gerade die initiale Therapie sollte neben der Wirksamkeit eine gute Verträglichkeit und Anwenderfreundlichkeit aufweisen. Kaliumhydroxid (KOH)-Lösung ist als keratolytische Behandlungsoption bei hyperkeratotischen Hauterkrankungen, wie z. B. Mollusca contagiosa, bereits etabliert. Methodik Wirksamkeit und Verträglichkeit von KOH-5 %-Lösung zur Behandlung der leichten bis moderaten AK wurden in einer prospektiven, einarmigen, multizentrischen Medizinproduktestudie (Treatment of AK with KOH [TAKKOH]) untersucht. Die KOH-Lösung wurde 2‑mal täglich über 14 Tage aufgetragen mit anschließender Behandlungspause von 14 Tagen (≙ 1 Behandlungszyklus) für maximal 3 Behandlungszyklen oder mindestens bis zum Behandlungserfolg. Das primäre Zielkriterium „Behandlungserfolg“ wurde als komplette Remission (CR) aller AK-Läsionen eines Patienten definiert. Sekundäre Zielkriterien beinhalteten die Beurteilung der partiellen Remission (PR), der Anzahl an AK-Läsionen in Remission, die Wirksamkeitsbeurteilung anhand von Schulnoten durch Prüfärzte und Patienten sowie sicherheitsrelevante Endpunkte. Ergebnisse Es wurden 73 Patienten in die Studie eingeschlossen. Eine CR wurde von 54,9 % der Patienten erreicht, eine PR von 64,8 % bei einer Reduktion der Gesamtzahl an Läsionen um 69,9 %. Bei 46,6 % der Patienten wurden unerwünschte Ereignisse beobachtet. Diese überwiegend unerwünschten Wirkungen (82,6 %) stellten ausnahmslos transiente und milde lokale Hautreaktionen dar. Schlussfolgerung Die Studie liefert Hinweise auf die Wirksamkeit und Sicherheit von KOH-5 %-Lösung zur läsionsgerichteten topischen Therapie der AK.

Background The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies. Objective To evaluate patient-reported outcomes, effectiveness and tolerability of patient self-applied MAL DL-PDT. Patients and methods An open study was conducted in Germany in patients with thin or non-hyperkeratotic and non-pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL-PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post-treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded. Results Patients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation). Conclusions Patient self-application of MAL DL-PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.

Background: Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair-skinned individuals. The World Health Organization distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC. Objective: To demonstrate noninferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of = -15%. Methods: The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm(-2)). The results shown include clinical end points and patients' reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013-003241-42). Results: Of the BF-200 ALA-treated patients, 93 4% were complete responders compared with 91 8% in the MAL group. The difference of means was 1 6, with a one-sided 97 5% confidence interval of -6 5, establishing noninferiority (P 0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were 10%. Conclusion: sTreatment of nonaggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven noninferiority to MAL-PDT. It demonstrates low recurrence rates after 1 year of follow-up. What's already known about this topic? Photodynamic therapy (PDT) using BF-200 aminolaevulinic acid (ALA) gel is registered and highly effective in the treatment of mild-to-moderate actinic keratosis and field cancerization. BF-200 ALA gel was recently approved for the treatment of superficial and/or nodular basal cell carcinoma (BCC) unsuitable for surgical treatment. PDT using methyl aminolaevulinate (MAL) cream is approved for the treatment of thin or nonhyperkeratotic and nonpigmented actinic keratoses, Bowen disease, and superficial and nodular BCCs when other therapies are considered less appropriate. What does this study add? BF-200 ALA-PDT is confirmed to be significantly noninferior to MAL-PDT for the treatment of nonaggressive BCC. Treatment-emergent adverse events were comparable between the two patient groups, with similar or slightly lower recurrence rates for BF-200 ALA gel compared with MAL cream after 12 months.

Background The most effective treatment modality for actinic keratosis (AK) is photodynamic therapy (PDT). Major obstacles of PDT are the need of a special illumination device and pain accompanying the illumination. These issues may be overcome by replacing an artificial high‐power light source with natural daylight for more extended illumination at lower light doses. Objective To determine whether BF‐200 ALA (a nanoemulsion gel containing 7.8% 5‐aminolaevulinic acid) is non‐inferior to MAL (a cream containing 16% methyl‐aminolaevulinate) in the treatment of mild‐to‐moderate AK with daylight PDT (dPDT). Non‐inferiority of the primary efficacy variable (total lesion clearance rate per patient's side 12 weeks after PDT) is established if the mean response for BF‐200 ALA is no worse than for MAL, within a statistical margin of Δ = −12.5%. Methods The study was performed as an intraindividual comparison with 52 patients in seven centres in Germany and Spain. Each patient received one dPDT. Results include clinical endpoints as well as 1‐year follow‐up results. Results Twelve weeks after a single dPDT, 79.8% of the AK lesions treated with BF‐200 ALA gel and 76.5% of the lesions treated with MAL cream were completely cleared. The median of differences was 0.0 with a one‐sided 97.5% CI of 0.0, establishing non‐inferiority (P < 0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 1 year after the treatment were 19.9% for lesions treated with BF‐200 ALA and 31.6% for lesions treated with MAL. Adverse reactions including pain were mostly mild and transient and identical to those previously described for dPDT. Conclusion Daylight PDT of AK with BF‐200 ALA is well‐tolerated and non‐inferior to MAL/dPDT. The study demonstrates a trend towards higher efficacies after 3 months and significantly lower recurrence rates after 1 year follow‐up.

Background Actinic keratoses (AKs) are clinically significant and require therapy. Efficacy of low-dose (0.5%) 5-fluorouracil with 10% salicylic acid (5-FU/SA) has been shown in randomized comparative trials of hyperkeratotic lesions of various grades. Objectives To evaluate the efficacy, tolerability and safety of low-dose 5-FU/SA topical solution vs. cryosurgery in patients with moderate/severe (grade II/III) hyperkeratotic AKs (NCT01358851). Methods In an exploratory, open, randomized study, patients with histologically confirmed moderate/severe hyperkeratotic AKs on the face/forehead or bald scalp received 6 weeks of once-daily topical 0.5% 5-FU/SA, or up to two cryosurgery treatments (3 weeks apart). Histological outcomes were determined from punch biopsies. Clinical, cosmetic and tolerability outcomes were also assessed. Results Sixty-six patients received treatment (33 per arm). The baseline total number of lesions was 266 (8.1/patient) in the 0.5% 5-FU/SA and 263 (8.0/patient) in the cryosurgery group. Most (74.5%) lesions were grade II (grade III, 25.5%). Mean change in lesion count from baseline to Day 98 was −5.2 and −5.7 lesions per patient for 0.5% 5-FU/SA and cryotherapy groups respectively. Histological AK clearance rates on Day 98 were 62.1% and 41.9% respectively. At 6-month posttreatment follow-up, recurrence of cleared lesions (no clinically visible lesions in treatment area) occurred in 39.4% of 0.5% 5-FU/SA and 84.8% of cryosurgery patients. Drug-related adverse events (AEs), including local skin reactions considered ‘severe’ by the investigator, were reported in 24.2% of 0.5% 5-FU/SA and 6.1% of cryosurgery patients. All drug-related AEs were skin reactions. Conclusions Although the study was not powered to explore statistical differences in clinical efficacy between treatments, a short (6-week) schedule of topical treatment with 0.5% 5-FU/SA achieved greater histological clearance and lower recurrence of grade II/III hyperkeratotic AKs than cryosurgery. AE incidence across both treatment groups was relatively low and AEs were generally mild or moderate. Clinical trials.gov identifier: NCT01358851.

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Two phase III trials of photodynamic therapy (PDT) with BF-200 ALA, a recently approved nanoemulsion formulation of 5-aminolaevulinic acid (ALA) demonstrated high clearance rates in mild-to-moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates.To evaluate long-term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF-200 ALA, MAL or placebo.The follow-up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF-200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT.Recurrence rates were similar for BF-200 ALA and MAL, with a tendency to lower recurrence rates for BF-200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF-200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF-200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported.The FUP data confirmed the high efficacy and safety of PDT with BF-200 ALA. The slightly lower recurrence rates after BF-200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy.

Background Chronic spontaneous urticaria (CSU), a mast cell-driven condition, is debilitating, common, and hard to treat. Miltefosine, a lipid raft modulator, can inhibit mast cell responses in vivo. Objective To study the safety and efficacy of systemic miltefosine treatment in CSU patients resistant to standarddosed antihistamines. Methods In this investigator-initiated multicentre, randomized, double-blind, placebo-controlled study, CSU patients were treated for 4 weeks with daily doses of up to 150-mg miltefosine (n = 47) or placebo (n = 26). Disease activity was assessed using the urticaria activity score. Safety and tolerability of miltefosine were also assessed. Results After 4 weeks of treatment, Urticaria Activity Score (UAS7) levels were substantially more reduced in miltefosine-treated patients ()6.3 vs. )3.5 in placebo-treated patients; P = 0.05). Also, the number of weals, but not the intensity of pruritus, was significantly reduced in miltefosine-treated patients vs. placebo-treated patients (P = 0.02). In general, adverse events were frequent in both groups (miltefosine: 88%, placebo: 65% of patients) but mostly mild to moderate in severity. We did not observe any serious adverse events. Conclusions The results of this study indicate that miltefosine is an effective and safe treatment option for CSU

Summary Background Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) or its methylester [methyl-5-aminolaevulinate (MAL) or 5-amino-4-oxopentanoate] was recently ranked as first-line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF-200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. Objectives To evaluate the efficacy and safety of PDT of AKs with BF-200 ALA in comparison with a registered MAL cream and with placebo. Methods The study was performed as a randomized, multicentre, observer-blind, placebo-controlled, interindividual trial with BF-200 ALA, a registered MAL cream and placebo in a ratio of 3 : 3 : 1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3 months after treatment, PDT was repeated. Results PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P

Summary Background Photodynamic therapy with a self-adhesive 5-aminolaevulinic acid (5-ALA) patch shows high efficacy rates in the treatment of mild to moderate actinic keratosis (AK) in short term trials. Objectives The purpose of the trial was to follow up patients after successful 5-ALA patch-PDT at 3 month intervals over a total period of 12 months. Patients who had received placebo-PDT or cryosurgery served for comparison. Patients/methods Three months after therapy, 360 patients from two separate randomized parallel group phase III studies (one superiority trial vs. placebo-PDT, one noninferiority trial vs. cryosurgery) were suitable for the follow-up study. Patients had to show at least one successfully treated AK lesion after initial therapy. A total of 316 patients completed the follow-up. Results Twelve months after a single treatment, 5-ALA patch-PDT still proved superior to placebo-PDT and cryosurgery (P

Not Available Study supported by Biofrontera.

Not AvailableStudy supported by Biofrontera.

In order to study the effect of toluene inhalation on the liver and kidney tissue trace element concentration levels, a study was done for 60 days involving 16 male Wistar rats. The control (Ce), 8 rats, were exposed to a stream of clean air only. The toluene exposed (Te), 8 rats, were subjected to 900 ppm of 99% pure toluene vapour. The exposure schedule was 6 hours per day, 5 days per week. Using Student's t test toluene inhalation decreased significantly the liver concentration levels of zinc. The results of this study also showed a significant increase in copper concentration levels caused by toluene inhalation in kidney tissues. The other trace elements, iron (Fe), manganese (Mn), cobalt (Co), cromium (Cr), nickle (Ni), and molybdenum (Mo), were also measured but their concentration levels were not significantly affected by toluene inhalation in this study. The results of this study suggest that toluene inhalation causes abnormal decrease of zinc concentration in the liver.

Summary Background Photodynamic therapy (PDT) is increasingly used for treatment of actinic keratoses (AKs) but is a cumbersome procedure. A thin self-adhesive patch (PD P 506 A) containing 5-aminolaevulinic acid (5-ALA) was developed to facilitate PDT. Objectives To investigate efficacy and safety of the patch in comparison with placebo–PDT (superiority design, observer-blinded; study AK 03) and standard therapy, cryosurgery (noninferiority design, open; study AK 04). Methods Two separate confirmatory randomized parallel-group phase III studies were set up. In total, 449 patients with up to eight mild to moderate AK study lesions located on the head were treated in 29 German study centres (study AK 03: 103 patients; study AK 04: 346 patients). Results Twelve weeks after treatment, 5-ALA patch–PDT proved to be superior to placebo–PDT (P

In trying to demonstrate the importance of preventive medicine in health care promotion, previous studies involving prevention and control of diseases have been discussed. Preventive medicine is also urged as the best method to help promoting health especially in the developing countries. Developed countries are urged to support developing countries, materially and financially in promoting their health. In terms of cost analysis prevention is an investment in health that produce a reduced probability of mortality and/or morbidity, therefore, we, investors in the developing countries, have to sacrifice something today in order to gain a benefit at a later point in time.

The effect of oral alcohol administration on branched-chain alpha-keto acids was studied in Wistar rats. Rats were divided into alcohol loading groups 1 (ethanol single daily dose: 2.5 g/kg body wt for 14 days) and 2 (ethanol dose: 5 g/kg body wt), and a pair-fed control group (isocaloric glucose and food equal to the amount taken by group 1 the previous day). Branched-chain alpha-keto acids, other alpha-keto acids and amino acids were analysed using high-performance liquid chromatography. Results showed a significant body weight increase in the alcohol loading groups. Concentrations of branched-chain amino acids and keto acids were significantly increased in the alcohol-treated groups. The blood levels of methionine, threonine, alanine and glutamic acid were also increased by alcohol administration. Blood levels of taurine and ornithine, however, showed a significant decrease in the alcohol-treated groups. These results show that alcohol increases the blood levels of branched-chain keto acids and branched-chain amino acids.