Palatability of two different formulations of urea for the treatment of hyponatremia: A double-blind, randomized, cross-over study.

BACKGROUND AND AIMS: Hyponatremia (HN) is the most common disorder of electrolytes encountered in clinical practice. Considering that HN is associated with high morbidity and mortality, it is important to identify treatments for these patients. The therapeutic approaches for HN depend on the severity and the character of the pathology (acute vs. chronic). Among intervention strategies, oral urea represents an effective, safe, and well-tolerated therapeutic approach in the management of chronic hyponatremia. Oral ureal is commonly prepared as a galenic formulation that is usually associated with distaste problems. A double-blind, randomized, cross-over clinical trial was conducted to evaluate and compare the palatability of two different urea formulations: a commercial urea formulation and a galenic one (trial registered on www.isrctn.com, number: ISRCTN18369035). MATERIALS AND METHODS: Thirty-six healthy subjects (18 female and 18 male, median age 55 years) were enrolled in the study and randomized to consume 7 g of formulation A (commercial formulation) or formulation B (galenic formulation) twice a day away from meals, solubilizing the products in 125 mL of water (T0). After three days of a wash-out, the formulations were crossed-over and consumed twice a day away from meals (T4). After the consumption of products, both in the morning and the evening, participants completed a specific questionnaire to evaluate the products' palatability. RESULTS: The commercial formulation was globally more appreciated than the galenic one, in terms of smell, taste, and aftertaste. The commercial formulation was better accepted as a potential treatment in 44 % of subjects compared to 14 % of subjects for galenic formulation. CONCLUSIONS: The clinical trial confirmed the better palatability of the commercial oral urea formulation, containing citrus flavor, which therefore represents a therapeutic strategy that could improve adherence to the therapy in chronic patients with hyponatremia.

Efficacy and tolerability of an oral supplement containing amino acids, iron, selenium, and marine hydrolyzed collagen in subjects with hair loss (androgenetic alopecia, AGA or FAGA or telogen effluvium). A prospective, randomized, 3-month, controlled, assessor-blinded study.

BACKGROUND: Oral supplementation with some amino acids (like methionine, taurine, and cysteine) could be useful in subjects with hair loss conditions such as androgenic alopecia (AGA or FAGA) or telogen effluvium (TE). Hydrolysed collagen (HC) oral supplementation has demonstrated to have beneficial effects on nail and skin health and could improve hair growth. A food supplement in tablet formulation containing hydrolysed fish-origin collagen (300 mg/dose), taurine, cysteine, methionine, iron, and selenium has been recently available. To date no controlled data are available regarding the clinical efficacy of this product as adjuvant to hair loss specific treatments in these clinical conditions. STUDY AIMS: To evaluate and compare the efficacy and tolerability of an oral supplementation based on HC and amino acids in subjects with hair loss due to AGA/FAGA or chronic TE in combination with drug treatments in comparison with drug treatments alone. METHODS AND SUBJECTS: In a prospective, 12-week, randomized, assessor-blinded controlled trial 83 subjects (mean age 41 ± 16 years; 26 men and 57 women) were enrolled in the study. Fifty-nine subjects suffered from AGA/FAGA (Hamilton I-VA, Ludwig I-1, II-2) and 24 from chronic TE. Subjects were randomized to oral supplementation (1 tablet day) in combination with the specify drug treatment decided by the investigator according to the type of hair loss (AGA/FAGA or TE) (Group A; N = 48) or to specific drugs treatment only (Group B; N = 35). The main outcome of the trial was the clinical efficacy evaluation using a 7-point global assessment score (GAS) (from +3: Much Improved to -3 Much worsened; with score 0 representing no modification). The GAS score was evaluated using standardized photographs by an investigator unaware of the treatment groups at week 6 and at week 12. A secondary outcome was the evaluation of acceptability of the treatment regimen using a 10-point evaluation score. RESULTS: Seventy-six participants (91.6%) completed the 12-week study period. The GAS score at week 6 was 0.5 ± 0.2 in group A and 0.0 ± 0.1 in Group B (p < 0.05; Mann-Whitney). At week 12 the GAS score in Group A was statistically significant higher in comparison with Group B (1.67 ± 0.16 and 0.66 ± 0.20, p < 0.001; Mann-Whitney test). A higher percentage of Group A subjects achieved a GAS score of ≥2 in comparison with group B (50% vs. 23%). The oral supplement was generally well tolerated. CONCLUSION: An oral supplement containing hydrolysed fish-origin collagen, taurine, cysteine, methionine, iron, and selenium has demonstrated to improve the clinical efficacy of specific anti-hair loss treatments in subjects with AGA/FAGA or chronic TE.

Efficacy of a retinoid complex plus anti-inflammatory component cream alone or in combination with prebiotic food supplement in adult acne: A randomized, assessor-blinded, parallel-group, multicenter trial on 184 women.

BACKGROUND: Adult female acne (AFA) nowadays is a very common skin condition affecting mainly women aged between 25 and 40. The treatment of AFA could be challenging. STUDY AIM: We evaluate and compare the efficacy and tolerability of a cream formulation containing two retinoid molecules (hydroxypinacolone/retinyl palmitate) combined with Iris Florentina root extract and a complex of three oligopeptides (C) applied twice a day (morning and evening) alone or in combination (C + O) with a food supplement containing a mixture of prebiotic molecules (FOS&GOS) zinc, lactoferrin, and niacinamide. SUBJECTS AND METHODS: In a multicenter, randomized, assessor-blinded, 12-week trial, we assessed the efficacy of these two regimens in the evolution of AFA lesions (non-inflammatory: NI-L; inflammatory: IL; and total number of lesions: TL). Additional efficacy endpoints were the evolution of the 6-point (from 0 to 5) GEA and Adult Female Acne Scoring Tool (AFAST) scores. RESULTS: One hundred and eighty-four women (mean age 32 ± 6 years) with AFA agreed to participate after obtaining informed consent. They were randomized (2:1) to the topical product (n = 123) (Group C) or to the combination (n = 61) (Group C + O) treatment. All enrolled patients concluded the trial with no drop-out. At baseline, NI-L, IL, and TL acne lesion count were 15 ± 9, 9 ± 5, and 24 ± 14 in the Group C and 19 ± 8, 9 ± 4, and 29 ± 10 in Group C + O. In comparison with the number of the acne lesions at the baseline, both treatment regimens induced a significant reduction (p = 0.0001, ANOVA test) at Week 12 in NI-L, IL, and TL by -54%, -63%, and - 59% in Group C and by -55%, -73%, and - 61% in the Group C + O, respectively. At Week 12, the absolute IL count reduction vs. baseline was significantly (p = 0.0158) greater in Group C + O (-7.0) in comparison with Group C (-5.5). The GEA absolute score reduction in Group C + O group was significantly greater in comparison with Group C (-1.5 vs. -1.1; p = 0.0097). In the Group C + O, a greater percentage of success treatment (defined as a GEA score of 0/1 at Week 12) was observed in comparison with Group C (39% vs. 27%; p = 0.06). AFAST score at baseline was 2.4 ± 0.5 in group C and 2.8 ± 0.6 in group C + O. AFAST score was reduced by 21% and by 51% after 6 and 12 weeks of treatment in group C and by 22% and 55% in group C + O, respectively. Both treatment regimens were well tolerated. Not relevant adverse events were recorded. CONCLUSION: A cream containing retinoid molecules and Iris Florentina root extract is effective and well tolerated in the management of AFA. The treatment combination with a prebiotic and anti-inflammatory food supplement offers an additional clinical benefit mainly in reducing inflammatory lesions and improving the severity acne score.

Efficacy of sinecatechins 10% as proactive sequential therapy of external genital warts after laser CO2 ablative therapy: The PACT study (post-ablation immunomodulator treatment of condylomata with sinecatechins): a randomized, masked outcome assessment, multicenter trial.

External genital warts (EGW) are the most common viral sexually transmitted infection. Ablative treatments like cryotherapy, curettage, and CO2 laser therapies offer rapid onset of effect, fast clearance, and reduction of virus load. However, these procedures are associated with high recurrence rates (RRs) ranging from 20% to 77% in the short and medium terms and do not provide sustained clearance. After laser therapy removal of EGW, an RR up to 77% has been reported. Topical sinecatechins (TS) 10% is a patient-applied regimen for the treatment of EGW with a low RR (<6.5%) at three months after completion of the therapy in the pivotal trials conducted so far. Sinecatechins can be considered a suitable proactive sequential therapy (PST) after ablative strategies to obtain a low RR. So far, no prospective data are available regarding the efficacy of sinecatechins 10% as PST. We evaluated the efficacy and tolerability of TS 10% ointment applied twice daily in subjects with "difficult to treat" EGW after CO2 laser ablative treatment in a prospective controlled trial. A total of 87 subjects (76 men and 11 women; mean age 42 years) were enrolled in this three-month masked outcome assessment parallel group trial with imbalanced randomization allocation (2:1). One week after a successful CO2 laser treatment, 60 subjects were randomized to TS 10% treatment and 27 subjects to no treatment (control group: ConTRol (CTR); no sequential therapy). All patients had a history of an average of 4.5 previous ablative treatments in the last 12 months due to recurrent EGW. Mean (standard deviation) baseline number of treated lesions was 6.5 (2.7). One subject in the TS arm dropped out due to burning sensation after the application of the product. Therefore, 86 subjects completed the study. After three months, in the TS group, three subjects presented new EGW lesions (RR: 5%) on treated sites. In the CTR group, eight subjects presented new EGW lesions (RR: 29%) on treated sites (p = 0.0024; odds ratio: 0.16; 95% confidence interval: 0.04-0.68). In the TS group, 34 subjects (56%) reported mild to moderate erythema or burning sensation at the application site. In this prospective multicenter trial, the use of TS 10% as PST after ablative treatment with CO2 laser was associated with a lower recurrence rate of new EGW lesions in the short term in comparison with the control group. Comparative larger trials are warranted to evaluate the role of this approach as PST (Trial Registration Number: ISRCTN44037479).

Efficacy of different photoprotection strategies in preventing actinic keratosis new lesions after photodynamic therapy. The ATHENA study: a two-center, randomized, prospective, assessor-blinded pragmatic trial.

Background: Treatment of actinic keratosis (AK) and field cancerization with photodynamic therapy (PDT) is an effective therapeutic approach with a significant reduction in the number of AK lesions (-75% or more) associated with a significant cosmetic improvement of the photodamaged skin. Recently, also, the daylight PDT (DL-PDT) has proven to be as effective as the conventional PDT (C-PDT), but with a better tolerability. After C-PDT and DL-PDT it is advised to use photoprotection strategies to improve the clinical evolution and prevent the appearance of new AK lesions that usually appear 3-6 months after the last phototherapy session. However, there are no robust clinical data regarding the type of photoprotection to be used (SPF level, duration of treatment, etc.) after successful PDT.Study aim: The present study (ATHENA trial) evaluated the efficacy and tolerability of a topical product based on 0.8% piroxicam and 50+ solar filters (ACTX), applied twice a day as sequential therapy after C-PDT or DL-PDT on the evolution of AK lesions number compared to the use of very high photoprotection products commonly used in this clinical setting (SPF50+ or SPF100+ associated with photolyase) (Standard Sunscreens: SS group). Subjects and methods: This was a multicenter, randomized, two-arm, prospective controlled, assessor-masked outcome evaluation, parallel group (1:1), pragmatic study of 6 months duration in patients with multiple AK lesions suitable for photodynamic therapy. The objectives of the study were the evaluation of the evolution of the number of AK lesions during the period of treatment/application of the study products, and the Investigator global clinical assessment score (IGA score; 4: marked improvement, 3: good, 2: moderate; 1 no improvement; 0: worsening) 2, 3, and 6 months after the last PDT session. A total of 68 subjects (50 men, 18 women; mean age 70 years), 34 assigned to treatment with ACTX and 34 to treatment with SS (17 treated with a SPF50+ and 17 with a photolyase-containing SPF100+ products), were enrolled in the study.Results: The number of AK lesions present before C-PDT/DL-PDT was 11.8 ± 5.8 in the ACTX group and 12.4 ± 6.9 in the SS group. In both groups, there was a progressive reduction of AK lesions observed at baseline (-86% and -87% after 2 months and -88% and -83% at month 3 in ACTX and in the SS group, respectively). At month 6, AK mean lesion number was 1.8 ± 1.6 in the ACTX and 3.2 ± 2.3 in the SS group; this difference was statistically significant (p = 0.03). The IGA score at the end of the study was 3.2 in the ACTX and 2.7 in the SS group (p = 0.05). The percentage of subjects with an IGA score of 4/3 (very good or good) was 81% in the ACTX and 55% in the SS group (p = 0.06).Conclusion: In subjects with AK treated with C-PDT or DL-PDT, a "medicalized" photoprotection treatment is associated with a favorable clinical outcome with progressive reduction of lesions. In contrast to a very high photoprotection (SPF50+ or SPF100+/photolyase), the use of piroxicam 0.8%/SPF 50+ is associated with a significantly greater improvement in clinical evolution of AK lesions.

Efficacy and Tolerability of Topical Green Tea Extract (Polyphenon E) Application in a "Therapy-Resistant" Plantar Wart.

Plantar warts account for 30% of all cutaneous warts. These lesions could be very painful, especially if the lesion is located over pressure sites such as the metatarsal head. Plantar wart treatment remains a challenging therapeutic problem. A 67-year-old immunocompetent nonsmoking man presented with a large mosaic plantar wart on his right foot. The lesion had been present for 5 years. Several cryotherapy sessions (a total of 6 procedures) had been performed with no success. The lesion was therefore treated with a 5-fluorouracil (5-FU) regimen and then with a topical combination of 5-FU and salicylic acid, but also these approaches failed. At the initial visit, a large (16 cm2) mosaic wart lesion was present. Treatment with topical Polyphenon E, 10%, twice daily was prescribed and started. After 3 months of treatment, the lesion completely disappeared. Interestingly, no curettage or mechanical pickling of the hyperkeratotic parts of the lesion were performed before the start of the treatment. Local tolerability was evaluated as very good by the patient.

A starch, glycyrretinic, zinc oxide and bisabolol based cream in the treatment of chronic mild-to-moderate atopic dermatitis in children: a three-center, assessor blinded trial.

BACKGROUND: Atopic dermatitis (AD) is a very common chronic inflammatory and eczematous skin condition characterized by flares and remissions. Skin barrier alteration or dysfunction is the most relevant patogenetic factor. Topical corticosteroids are the mainstay treatment of AD, especially during flare periods. The daily use of emollients and moisturizers is also considered a relevant adjunctive strategy to improve skin barrier function and skin appearance in AD patients. Long-term use of topical corticosteroids is associated with important drawbacks and side effects. A corticosteroid-free cream containing starch, glycyrretinic acid, zinc oxide and bisabolol (Dermamid™; Difa Cooper, Caronno Pertusella, Varese, Italy) has been designed for the treatment of acute eczematous conditions like diaper dermatitis. However, this formulation could be particularly suitable also for AD. We evaluated in a three-center, assessor-blinded prospective 6-week treatment trial the efficacy and tolerability of this cream in children with chronic mild-to-moderate atopic dermatitis. METHODS: A total of 30 children (mean age 5 years, 18 males and 12 females) with chronic mild to moderate AD, affecting face, lower and upper limbs or trunk, were enrolled after parents' written informed consent. Exclusion criteria were a condition of immunosuppression, acute flares or a positive history of allergy to one of the components of the cream. The primary outcome was the evolution total eczema severity score (TESS) calculated as the sum of the single eczema severity score for each body area involved. Single area Eczema Severity Score (ESS) was calculated assessing eczema, infiltration, lichenification and scraching lesions using a 4-point scale grade (with 0=no sign, and 4=severe sign). A secondary endpoint was the percentage of subjects reaching at least 50% of TESS reduction at week 6 in comparison with baseline. The TESS was evaluated at baseline and after 3 and 6 weeks of treatment (twice daily application) in an assessor-blind fashion. RESULTS: At baseline the mean (SD) TESS was 11.6 (4.7). TESS was reduced significantly (P=0.0001) to 5.7 (3) after 3 weeks (-51%), and to 3.0 (2.3) at week 6 (-74%). Similar reductions were observed for single area ESS values. The percentage of subjects with at least a >50% reduction of TESS value at the end of the study was 87%. The product was very well tolerated. Only for one patient a mild burning sensation at the application site was reported. All the subjects concluded the trial. CONCLUSIONS: This trial supports the efficacy and the tolerability of a corticosteroid-free cream containing starch, glycyrretinic acid and bisabolol in the treatment of chronic mild to moderate atopic dermatitis in children.

Protective effects of Polypodium leucotomos extract against UVB-induced damage in a model of reconstructed human epidermis.

BACKGROUND: Polypodium leucotomos (PL) exerts potent antioxidant, photo-protective, and immune-modulatory activities. A reconstructed human epidermis (RHE) (Episkin) is a suitable model for the evaluation of acute UV-induced cell damage. No data regarding the photo-protective action of PL in this model are available. PURPOSE: We evaluated the effects of PL on the prevention of UVB-induced cell damage assessing sunburn cells, CPD formation, p53, Ki-67, p21 expression, and epidermal growth factor (EGF) production. MATERIALS & METHODS: RHE was incubated in standard conditions. PL was topically applied at the concentration of 2 mg/cm2 , immediately before UVB exposition. UVB exposition (300 mJ/cm2 ) was performed using a dedicated UVB lamp. Irradiated samples without PL and non-irradiated samples were used as positive and negative controls. Expression of p53, p21, and Ki-67 was evaluated with immune-histochemical methods. CPD were measured using a monoclonal antibody. RESULTS: PL significantly reduced sunburned cells (-80%) in comparison with positive control. PL significantly prevented the increase in EGF production at tested times. PL significantly reduced the p53 (-80%), p21 (-84%), and Ki-67 (-48%) positive cells. Finally, PL prevented the formation of CPD (0% vs. 20% positive cells). CONCLUSION: In this model, PL has shown to prevent UVB cell damage, the upregulation of proliferating proteins, and fully blocking the formation of CPD.

Biorevitalizing effect of a novel facial serum containing apple stem cell extract, pro-collagen lipopeptide, creatine, and urea on skin aging signs.

BACKGROUND: Epithelial regeneration in skin is achieved by the constant turnover and differentiation of keratinocytes. Epidermal and dermal stem cells compartments are fundamental for the continuous renewal of the skin. Adult stem cells are the unique source for skin tissue renewal. Plants have stem cells and plant derived stem cell extracts are now used in topical products for their potential anti-ageing and anti-wrinkle effects. A new dermocosmetic product containing apple stem cell extract, urea, creatine and palmitoyl tripeptide-38 (Ureadin Fusion Serum Lift Antiarrugas, ISDIN S.A), has been recently developed to target different aspects involved in skin aging. STUDY AIM: To assess in vitro the effects of this new serum on the metabolic functions of human senescent fibroblasts and in vivo the anti-aging effects by clinical and instrumental evaluation. METHODS: We evaluated the effects of the serum on the mitochondrial ROS (reactive oxygen species) production in human senescent cultured fibroblasts measured at 0.1% and 1% using the Mitoread AntiOx mtROS method. In addition we evaluated the anti-ageing in vivo effect of this new serum applied on the face twice daily for 28 consecutive days and assessed by clinical and instrumental evaluation in 32 women with sensitive skin bearing wrinkles on crow's feet. RESULTS: The tested serum both at 0.1% and 1% induces a significant increase in 02 consumption, cellular ATP level and a reduction in extra-cellular lactate concentration. The product reduces also significantly the mitochondrial ROS production. The clinical study shows a relevant anti-wrinkle effect in 71% of the treated women with visible effects in 68% of the subjects as soon as 7 days of treatment. A significant increase in dermal density and skin elasticity was also observed. CONCLUSION: The use of this novel anti-aging serum demonstrated a significant improvement of aging skin signs with first visible results achieved after one week of use. The product seemed to optimize the metabolic functions in human senescent cultured fibroblast restoring a more efficient cell metabolism therefore contributing to the anti-aging properties of the product.

Adherence to drug treatments and adjuvant barrier repair therapies are key factors for clinical improvement in mild to moderate acne: the ACTUO observational prospective multicenter cohort trial in 643 patients.

BACKGROUND: In acne, several studies report a poor adherence to treatments. We evaluate, in a real-life setting conditions, the impact of compliance to physician's instructions, recommendations and adherence to the treatments on clinical outcome in patients with mild to moderate acne in an observational, non-interventional prospective study carried out in 72 Dermatologic Services in Spain (ACTUO Trial). METHODS: Six-hundred-forty-three subjects were enrolled and 566 patients (88 %) completed the 3 study visits. Study aimed to evaluate the impact of adherence (assessed with ECOB scale) on clinical outcome, as well as how the use of specific adjuvant treatments (facial cleansing, emollient, moisturizing and lenitive specific topical products) influences treatment's adherence and acne severity (0-5 points score). Recommendation of specific adjuvant skin barrier repair products was made in 85.2 %. RESULTS: Overall, clinical improvement was observed throughout follow-up visits with an increased proportion of patients who reported reductions of ≥50 % on the total number of lesions (2 months: 25.2 %; 3 months: 57.6 %) and reductions of severity scores (2.5, 2.0 and 1.3 at 1, 2 and 3 months after treatment, respectively). Adherence to treatment was associated with a significant reduction on severity grading, a lower number of lesions and a higher proportion of patients with ≥50 % improvement. CONCLUSIONS: Good adherence to medication plus adherence to adjuvants was significantly associated with a higher clinical improvement unlike those that despite adherence with medication had a low adherence to adjuvants. A good adherence to adjuvant treatment was associated with improved adherence and better treatment outcomes in mild to moderate acne patients. (ISRCTN Registry: ISRCTN14257026).

Allergy immunotherapy tablet: Grazax® for the treatment of grass pollen allergy.

Immunotherapy is the only treatment for allergy that alters the natural course of this disease. Sublingual immunotherapy has been developed to make immunotherapy more suitable for allergic patients. In the largest clinical program ever conducted with grass allergen-specific immunotherapy, over 2000 adults and more than 500 children have been exposed to Grazax(®) (ALK-Abello A/S, Hoersholm, Denmark). Grazax is an oral lyophilisate tablet (allergy immunotherapy tablet [AIT]) for sublingual administration, containing 75,000 standardized quality tablet units of allergen extract of grass pollen (Phleum pratense). Grazax is indicated for treatment of grass pollen-induced rhinitis and conjunctivitis in adult and pediatric patients. Results from the GT-08 trial (first, second and third treatment years) showed a reduction of 31, 36 and 29%, respectively, in symptom scores and a reduction of 38, 45 and 40% of medication scores, respectively, compared with placebo. Subjects treated with Grazax also had an increased number of well days and a relevant improvement in quality of life. More subjects experienced excellent and complete rhinoconjunctivitis control in comparison with patients treated with symptomatic medications only. Grazax treatment is also associated with a sustained and relevant increase of specific IgG4. This increase is also observed after stopping AIT treatment. The most common adverse events related to Grazax treatment are local reactions, such as oral itch, edema of the mouth, ear pruritus, throat irritation and sneezing. Clinical efficacy of Grazax is observed also after 1 and 2 years of follow-up after stopping the AIT treatment. Grazax is efficacious and safe for treatment of grass-pollen rhinoconjunctivitis in both adults and children. Grazax is the first AIT showing a disease-modifying effect on grass pollen-induced allergic rhinoconjuctivitis.