Preclinical pharmacokinetic investigation of the bioavailability and skin distribution of HY-072808 ointment, a novel drug candidate for the treatment of atopic dermatitis, in minipigs by a newly LC-MS/MS method.

HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC-MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1-7.6% after transdermal application of 1-4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug.

Tirbanibulin 1% Ointment for Actinic Keratosis: Results from a Real-Life Study.

Background and Objectives: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods: We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients-28 males (73%) and 10 females (26%)-aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results: Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs.

Efficacy and safety of crisaborole ointment, 2%, in participants aged ≥45 years with stasis dermatitis: Results from a fully decentralized, randomized, proof-of-concept phase 2a study.

BACKGROUND: Crisaborole ointment, 2%, is a nonsteroidal topical phosphodiesterase 4 inhibitor approved for the treatment of mild-to-moderate atopic dermatitis. OBJECTIVE: To evaluate the efficacy and safety of crisaborole in stasis dermatitis (SD). METHODS: In this randomized, double-blind, vehicle-controlled, decentralized phase 2a study (NCT04091087), 65 participants aged ≥45 years with SD without active ulceration received crisaborole or vehicle (1:1) twice-daily for 6 weeks. The primary end point was percentage change from baseline in total sign score at week 6 based on in-person assessment. RESULTS: Crisaborole-treated participants had significantly reduced total sign score from baseline versus vehicle based on in-person (nondermatologist) assessment (-32.4% vs -18.1%, P = .0299) and central reader (dermatologists) assessment of photographs (-52.5% vs -10.3%, P = .0004). Efficacy according to success and improvement per Investigator's Global Assessment score and lesional percentage body surface area reached statistical significance based on central reader but not in-person assessments. Skin and subcutaneous tissue disorders were common all-causality treatment-emergent adverse events with crisaborole. LIMITATIONS: Small sample size and short treatment duration were key limitations. In-person assessment was not conducted by dermatologists. CONCLUSION: Crisaborole improved signs and symptoms of SD and was well tolerated. Central reader assessment represents a promising approach for siteless clinical research.

Comparative efficacy of Salix aegyptiaca's active compound versus phenytoin in healing full-thickness rat skin wounds: An animal model study.

BACKGROUND: Wound healing poses a challenging therapeutic scenario, requiring diverse clinical approaches. OBJECTIVES: This study aims to assess the wound-healing potential of Salix aegyptiaca's flower ointment compared to phenytoin, considering the active constituents of S. aegyptiaca and its traditional usage. METHODS: Initially, the active components of S. aegyptiaca were isolated and identified through the GC-MS technique. Subsequently, for the experimental intervention, thirty-five rats were divided into five distinct groups: control (C), phenytoin (F), and three S. aegyptiaca ointment groups at different concentrations (5 % - S5, 25 % - S25, and 50 % - S50). Anesthesia was administered, and wounds were induced on the animals' necks following a standard procedure. These wounds were then treated for a duration of 21 days. Wound healing progress was quantified, and histopathological assessments were conducted using hematoxylin and eosin staining and Mason's trichrome staining. RESULTS: The main active compounds of S. aegyptiaca, namely n-hexadecanoic acid and oleic acid, were identified via GC-MS analysis. Although the initial group weights did not show a significant difference (P = 0.271), a significant variation was observed in the final weights (P = 0.003). The S50 group exhibited a lower wound healing rate than the S25 group on the 7th and 14th days but surpassed it on the 21st day (C < F < S5≈S25

Treatment of hypopigmented burn hypertrophic scars with short-term topical tacrolimus does not lead to repigmentation.

OBJECTIVES: Dyschromia is an understudied aspect of hypertrophic scar (HTS). The use of topical tacrolimus has successfully shown repigmentation in vitiligo patients through promotion of melanogenesis and melanocyte proliferation. It was hypothesized that HTSs treated with topical tacrolimus would have increased repigmentation compared to controls. METHODOLOGY: Full-thickness burns in red Duroc pigs were either treated with excision and meshed split-thickness skin grafting or excision and no grafting, and these wounds formed hypopigmented HTSs (n = 8). Half of the scars had 0.1% tacrolimus ointment applied to the scar twice a day for 21 days, while controls had no treatment. Further, each scar was bisected with half incurring fractional ablative CO2 laser treatment before topical tacrolimus application to induce laser-assisted drug delivery (LADD). Pigmentation was evaluated using a noninvasive probe to measure melanin index (MI) at Days 0 (pretreatment), 7, 14, and 21. At each timepoint, punch biopsies were obtained and fixed in formalin or were incubated in dispase. The formalin-fixed biopsies were used to evaluate melanin levels by H&E staining. The biopsies incubated in dispase were used to obtain epidermal sheets. The ESs were then flash frozen and RNA was isolated from them and used in quantitative reverse transcription polymerase chain reaction for melanogenesis-related genes: Tyrosinase (TYR), TYR-related protein-1 (TYRP1), and dopachrome tautomerase (DCT). Analysis of variance test with Sídák's multiple comparisons test was used to compare groups. RESULTS: Over time, within the grafted HTS and the NS group, there were no significant changes in MI, except for Week 3 in the -Tacro group. (+Tacro HTS= pre = 685.1 ± 42.0, w1 = 741.0 ± 54.16, w2 = 750.8 ± 59.0, w3 = 760.9 ± 49.8) (-Tacro HTS= pre = 700.4 ± 54.3, w1 = 722.3 ± 50.7, w2 = 739.6 ± 53.2, w3 = 722.7 ± 50.5). Over time, within the ungrafted HTS and the NS group, there were no significant changes in MI. (+Tacro HTS= pre = 644.9 ± 6.9, w1 = 661.6 ± 3.3, w2 = 650.3 ± 6.2, w3 = 636.3 ± 7.4) (-Tacro HTS= pre = 696.8 ± 8.0, w1 = 695.8 ± 12.3, w2 = 678.9 ± 14.0, w3 = 731.2 ± 50.3). LADD did not lead to any differential change in pigmentation compared to the non-LADD group. There was no evidence of increased melanogenesis within the tissue punch biopsies at any timepoint. There were no changes in TYR, TYRP1, or DCT gene expression after treatment. CONCLUSION: Hypopigmented HTSs treated with 0.1% tacrolimus ointment with or without LADD did not show significantly increased repigmentation. This study was limited by a shorter treatment interval than what is known to be required in vitiligo patients for repigmentation. The use of noninvasive, topical treatments to promote repigmentation are an appealing strategy to relieve morbidity associated with dyschromic burn scars and requires further investigation.

Efficacy of Qingpeng ointment (a Tibetan medicine) for acute gouty arthritis: a multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study aims to assess the efficacy and safety of Qingpeng ointment (QPO), a Tibetan medicine for alleviating symptoms in individuals with acute gouty arthritis (AGA). METHODS: This study was a randomized, double-blind, placebo-controlled trial that involved individuals with AGA whose joint pain, as measured on a visual analog scale (VAS) from 0 to 10, was equal to or greater than 3. The participants were randomly assigned to either the QPO or the placebo group and received their respective treatments twice daily for seven consecutive days. In case of intolerable pain, the participants were allowed to use diclofenac sodium sustained-release tablets as a rescue medicine. The primary outcomes measured were joint pain and swelling, while the secondary outcomes included joint mobility, redness, serum uric acid levels, C-reactive protein levels, and the amount of remaining rescue medicine. Any adverse events that occurred during the trial were also recorded. RESULTS: A total of 203 cases were divided into two groups, with balanced baselines: 102 in the QPO group and 101 in the placebo group. For joint pain, differences between the groups were notable in the VAS scores [1.75 (0, 3.00) versus 2.00 (1.00, 3.50); P = 0.038], changes in VAS [5.00 (3.00, 6.00) versus 4.00 (2.00, 6.00); P = 0.036], and disappearance rate [26.47% compared to 15.84%; P = 0.046] after treatment. Concerning joint swelling, significant between-group differences were observed in the VAS scores [1.00 (0, 2.30) versus 2.00 (0.70, 3.00); P = 0.032] and disappearance rate [33.33% compared to 21.78%; P = 0.046] at treatment completion. The QPO group exhibited a statistically significant mobility improvement compared to the placebo group (P = 0.004). No significant differences were found in other secondary outcomes. Five patients, four from the QPO group and one from the other, encountered mild adverse events, primarily skin irritation. All of these cases were resolved after dosage reduction or discontinuation of the medication. CONCLUSIONS: Compared to the placebo, QPO exhibits positive effects on AGA by alleviating pain, reducing swelling, and enhancing joint mobility, without causing significant adverse effects. TRIAL REGISTRATION: ISRCTN34355813. Registered on 25/01/2021.

Topical tacrolimus in high-risk corneal transplants.

PURPOSE: The purpose of this study was to assess the use of topical tacrolimus ointment in preventing rejection in high-risk corneal grafts, when added to the standard immunosuppressive regimen. METHODS: We conducted an observational, retrospective study using clinical data of high-risk patients subjected to penetrating keratoplasty, who were treated with topical tacrolimus ointment 0.2 mg/g twice a day plus topical dexamethasone 0.1 mg/ml 6 id and compared it with a similar control group treated with topical dexamethasone 0.1 mg/ml 6 id alone. High-risk status was attributed to patients with previous ipsilateral corneal graft failure, two or more quadrants with corneal neovascularization or an infectious or inflammatory corneal disease. RESULTS: We analysed 53 patients in the trial group versus 53 patients in the control group, with similar age, baseline diagnosis and risk factors, and median follow-up times of 30 and and 24 months, respectively. Survival analysis showed a higher graft survival rate at all follow-up periods for patients treated with topical tacrolimus (p < 0.01). No adverse reactions were reported. DISCUSSION: This study shows that topical tacrolimus ointment increases the survival rate of the graft if added to the previous topical steroid regimen in high-risk patients. CONCLUSION: Topical tacrolimus is safe and effective in prolonging graft survival in high-risk patients.

Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study.

BACKGROUND: Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. METHODS: This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion. RESULTS: A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were -73.5% at week 4, -81.7% at week 28, and -81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%-95.2%). CONCLUSIONS: Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.

Efficacy and safety of tirbanibulin 1% ointment in actinic keratoses: Data from two phase-III trials and the real-life clinical practice presented at the European Academy of Dermatology and Venereology Congress 2022.

BACKGROUND: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. OBJECTIVES: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. METHODS: Summary of presentations given at the EADV Congress. RESULTS: Prof. Pellacani presented two post hoc analyses from two phase-III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real-life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2- to 4-month follow-up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1-2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real-world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. CONCLUSIONS: This article provides an overview of presentations and symposium discussions, summarizing key phase-III results and real-life clinical experience with tirbanibulin shared by dermatologists across Europe.

Efficacy and Safety of PF-07038124 in Patients With Atopic Dermatitis and Plaque Psoriasis: A Randomized Clinical Trial.

Importance: Atopic dermatitis (AD) and plaque psoriasis are inflammatory skin diseases with unmet need for effective topical treatments with few application site reactions. Objective: To assess the efficacy and safety of the topical phosphodiesterase 4 inhibitor PF-07038124 in patients with AD and plaque psoriasis. Design, Setting, and Participants: This phase 2a, randomized, double-blind clinical trial was conducted from December 21, 2020, to August 18, 2021, at 34 sites across 4 countries. Eligible patients (aged 18-70 years) had mild to moderate AD (covering 5%-20% body surface area) or plaque psoriasis (covering 5%-15% body surface area). Data were analyzed until December 15, 2021. Interventions: Patients were randomized (1:1) to PF-07038124, 0.01%, topical ointment or vehicle once daily for 6 weeks. Main Outcomes and Measures: The primary end point was the percent change from baseline (CFB) in the Eczema Area and Severity Index (EASI) total score among patients with AD and in the Psoriasis Area and Severity Index (PASI) score among patients with plaque psoriasis at week 6. Safety measures included treatment-emergent adverse events, including application site reactions. Results: Overall, 104 patients were randomized (mean [SD] age, 43.0 [15.4] years; 55 [52.9%] women; 4 [3.8%] Asian, 13 [12.5%] Black, and 87 [83.7%] White), including 70 with AD (41 women [58.6%]; mean [SD] ages, 41.4 [16.6] years in the PF-07038124 group and 36.1 [13.9] years in the vehicle group) and 34 with plaque psoriasis (20 men [58.8%]; mean [SD] ages, 51.8 [12.3] years in the PF-07038124 group and 51.2 [10.8] years in the vehicle group). Baseline characteristics were generally balanced. At week 6, the PF-07038124 groups showed significantly greater improvements compared with vehicle groups in EASI (least-squares mean CFB, -74.9% vs -35.5%; difference, -39.4% [90% CI, -58.8% to -20.1%]; P < .001) and PASI scores (CFB, -4.8 vs 0.1; difference, -4.9 [90% CI, -7.0 to -2.8]; P < .001). The number of patients with treatment-emergent adverse events was comparable between treatment groups in patients with AD (PF-07038124, 9 [25.0%]; vehicle, 9 [26.5%]) and plaque psoriasis (PF-07038124, 3 [17.6%]; vehicle, 6 [35.3%]). There were no application site reactions with PF-07038124 treatment. Conclusions and Relevance: Topical PF-07038124 was well tolerated and demonstrated superior efficacy compared with vehicle in patients with mild to moderate AD and plaque psoriasis. Trial Registration: ClinicalTrials.gov Identifier: NCT04664153.

Application Site of Transdermal Scopolamine Influences Efficacy and Drug Concentration in Salivary Glands in Rats.

Transdermal scopolamine applied to the postauricular area is used to treat drooling. We investigated the duration of action of scopolamine ointment and the effect of the application site on drug efficacy and concentration in the salivary glands of rats. Scopolamine ointment was applied to the skin over the salivary glands (SSG) and back (SB). Saliva volume was measured after intraperitoneal administration of pilocarpine. Blood and salivary glands were collected after scopolamine ointment application, and scopolamine concentrations in the plasma and salivary glands were measured. Saliva volume after application in the SSG group was significantly lower at all time points than in the non-treated group, and the change in saliva volume in the SSG group was greater than that in the SB group at all time points. This suggests that applying scopolamine ointment to the SSG strongly suppresses salivary secretion. Scopolamine concentration in the salivary glands of the SSG group was significantly higher at 9 h. The change in the efficacy of scopolamine ointment depending on the application site was due to the difference in transfer to the salivary glands. Transdermal administration of scopolamine to the skin over the salivary glands may have high efficiency in treating drooling.

Antileishmaniasis effects of monoherbal skin ointment made from bark and leaf of Holoptelea integrifolia (Roxb.) Planch. in patients of cutaneous leishmaniasis.

Prevalence of parasitic skin diseases, cutaneous leishmaniasis is very frequent in Pakistan, especially in Baluchistan where occurrence of phelbotomine sand flies (vector of protozoan parasite of genus Leishmania) is very common. This study was conducted to assess the antileishmaniasis activity of Intericutol plus ointment (2% and 3%) made with ethanolic extract of bark and leaves of Holoptelea integrifolia (Roxb.)Planch. The antileishmaniasis effect was observed by applying the ointments on the lesions of leishmaniasis patients. 150 patients were included in the study that had single and multiple painful wet and dry ulcerative lesions on the exposed area of the body. The patients were divided into two groups of 75 patients each, applying 2% and 3% ointment respectively for 28 days. Dose of 10gm/week was applied topically on wounds. Excellent antileishmaniasis effect was observed with significant quick healing properties in the patients receiving 3% Intericutol plus ointment as compare to 2% showing 89% and 81% cure (p=0.02) respectively. It can be concluded that ointment made from medicinal plant proved to be very effective in treating cutaneous Leishmaniasis.

Comparison of lotions, creams, gels and ointments for the treatment of childhood eczema: the BEE RCT.

Background: Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing. Objective: To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema. Design: Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks. Setting: Primary care (78 general practitioner surgeries) in England. Participants: Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents. Interventions: Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked. Main outcome measures: The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks. Results: A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2-8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global p = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences - cream-lotion 0.42 (95% confidence interval -0.48 to 1.32), gel-lotion 0.17 (95% confidence interval -0.75 to 1.09), ointment-lotion -0.01 (95% confidence interval -0.93 to 0.91), gel-cream -0.25 (95% confidence interval -1.15 to 0.65), ointment-cream -0.43 (95% confidence interval -1.34 to 0.48) and ointment-gel -0.18 (95% confidence interval -1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and topical corticosteroids was similar across groups. Overall satisfaction was highest for lotions and gels. There was no difference in the number of adverse reactions and there were no significant adverse events. In the nested qualitative study (n = 44 parents, n = 25 children), opinions about the acceptability of creams and ointments varied most, yet problems with all types were reported. Effectiveness may be favoured over acceptability. Parents preferred pumps and bottles over tubs and reported improved knowledge about, and use of, emollients as a result of taking part in the trial. Limitations: Parents and clinicians were unmasked to allocation. The findings may not apply to non-study emollients of the same type or to children from more ethnically diverse backgrounds. Conclusions: The four emollient types were equally effective. Satisfaction with the same emollient types varies, with different parents/children favouring different ones. Users need to be able to choose from a range of emollient types to find one that suits them. Future work: Future work could focus on how best to support shared decision-making of different emollient types and evaluations of other paraffin-based, non-paraffin and 'novel' emollients. Trial registration: This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment; Vol. 27, No. 19. See the NIHR Journals Library website for further project information.

One in five children in the UK have eczema, a long-term, itchy, dry skin condition. It can significantly affect both the child and their family. Most children are diagnosed and looked after by their family doctor (general practitioner) and are prescribed moisturisers (also called emollients) to relieve skin dryness and other creams (topical corticosteroids) to control flare-ups. However, there are many different types of emollients and, to our knowledge, limited research to show which is better. In the Best Emollients for Eczema clinical trial, we compared the four main types of moisturisers ­ lotions, creams, gels and ointments. These types vary in their consistency, from thin to thick. We recruited 550 children (most of whom were white and had moderate eczema) and randomly assigned them to use one of the four different types as their main moisturiser for 16 weeks. We found no difference in effectiveness. Parent-reported eczema symptoms, eczema severity and quality of life were the same for all the four types of moisturisers. However, overall satisfaction was highest for lotions and gels. Ointments may need to be used less and cause less stinging. We interviewed 44 parents and 25 children who took part. Opinions of all four types of moisturisers varied. What one family liked about a moisturiser was not necessarily the same for another and preferences were individual to each user. Sometimes there was a tension between how well a moisturiser worked (effectiveness) and how easy it was to use (acceptability). In these cases, effectiveness tended to decide whether or not parents kept using it. People found moisturisers in pumps and bottles easier to use than those in tubs. A number of participants valued the information they were given about how to use moisturisers. Our results suggest that the type of moisturiser matters less than finding one that suits the child and family.

Comparison of ointment-based agents after excisional procedures for hemorrhoidal disease: a network meta-analysis of randomized controlled trials.

INTRODUCTION: Efficient postoperative pain control is important after hemorrhoidal surgery. Although several locally applied medications have been used, current evidence regarding the optimal strategy is still conflicting. This network meta-analysis assessed analgesic efficacy and safety of the various topical medications in patients submitted to excisional procedures for hemorrhoids. METHODS: The present study followed the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. The last systematic literature screening was performed at 15 June 2023. Comparisons were based on a random effects multivariate network meta-analysis under a Bayesian framework. RESULTS: Overall, 26 RCTs and 2132 patients were included. Regarding postoperative pain, EMLA cream (surface under the cumulative ranking curve (SUCRA) 80.3%) had the highest ranking at 12-h endpoint, while aloe vera cream (SUCRA 82.36%) scored first at 24 h. Metronidazole ointments had the highest scores at 7 and 14 days postoperatively. Aloe vera had the best analgesic profile (24-h SUCRA 84.8% and 48-h SUCRA 80.6%) during defecation. Lidocaine (SUCRA 87.9%) displayed the best performance regarding overall morbidity rates. CONCLUSIONS: Due to the inconclusive results and several study limitations, further RCTs are required.

Autonomic dysreflexia: Current pharmacologic management.

BACKGROUND: Autonomic dysreflexia (AD) is a frequent complication of spinal cord injury (SCI), though current clinical practice patterns for medication management of this condition are unknown. Correspondingly, it is unclear if national differences in practice patterns exist. OBJECTIVE: To determine trends in current pharmacologic management of AD throughout the Americas. DESIGN: International survey of current physician practice patterns. SETTING: Academic medical center. PARTICIPANTS: Sixty physicians managing patients with SCI and prescribing medications to manage AD. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Presence of a formal pharmacologic AD management protocol, first- and second-line medications, patient characteristics influencing pharmacologic management. RESULTS: The majority of physicians (69%) had a formal AD management protocol for inpatient care, with nitroglycerin ointment (82%) being the most common first-line medication. Strong national differences existed regarding the use of nitroglycerin ointment, with 98% of U.S.-based physicians using this as first-line medication and 0% of physicians in Canada or Latin America using this due to recent lack of medication availability. Only 67% of physicians had a preferred second-line medication, with preferences split between hydralazine (48%) and nifedipine (28%). A systolic blood pressure threshold for pharmacologic management was used by 56% of physicians, wheres 26% considered neurological level of injury in decisions to use medications for AD. Heart rate was used by only 5% of physicians in their decision to manage AD with medications. CONCLUSIONS: As of 2023, U.S.-based physicians caring for individuals with SCI largely have formal inpatient protocols in place for medication management of AD, with nearly all relying on nitroglycerin ointment as their first-line medication. In areas outside of the United States where nitroglycerin ointment is unavailable, pharmacologic practice patterns significantly differ.

Clinical characteristics, treatment outcomes, and prognosis in patients with MKIs-associated hand-foot skin reaction: a retrospective study.

BACKGROUND: Multikinase inhibitors (MKIs) treatment has been proven as a powerful strategy in cancer therapy. However, it is greatly hampered by its common adverse effect known as hand-foot skin reaction (HFSR), especially in patients with moderate-to-severe HFSR. OBJECTIVE: To investigate the clinical characteristics, histopathological features, treatment response, and bio-indicators of HFSR. METHODS: We retrospectively reviewed the medical records of 102 patients with moderate-to-severe HFSR resulting from MKIs therapy. RESULTS: The median time to development of moderate-to-severe HFSR was 18 days, which would be significantly affected by the type of MKIs and the history of HFSR. Notably, we found that HFSR was classified into three consecutive stages: erythematous lesion, yellow hyperkeratotic lesion with surrounding erythema, and hyperkeratotic lesion. Inflammation was observed in the first two stages of HFSR, but disappeared in the third stage; in contrast, the hyperkeratosis gradually became thicker from stage one to stage three. Moreover, topical medications were demonstrated as an effective therapy for HFSR, among which, the topical steroids and urea ointment treatment response rate was 37.14%, the Shouzu Ning Decoction (SND) treatment response rate was 65%, and the SND in combination with urea ointment treatment response rate was 75%, meanwhile, systemic therapies did not improve the therapeutic efficacy of topical medications alone. In addition, the serum levels of HMGB1 were found to be a potential indicator for tracking the healing process as well as predicting the prognosis of HFSR. CONCLUSION: This study revealed the potential factors affecting the development of HFSR, evaluated the therapeutic response towards different strategies for treating HFSR, and identified a potential prognostic indicator of HFSR.

Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: Atopic dermatitis (AD, also called atopic eczema) is a skin disease that that can affect a person for a long time and causes red or flaky skin that can be itchy and uncomfortable. Healthcare providers can prescribe medicated creams and ointments to reduce the visible signs and symptoms of AD, but these treatments are not always enough to keep it under control. A new medicine called abrocitinib is taken every day as a tablet. Abrocitinib works by slowing a part of the body's defense mechanism, called immune response, that is not functioning properly in AD. The clinical study described in this plain language summary, called JADE DARE, investigated how well and how safely 26 weeks of treatment with abrocitinib worked in adults with AD compared to an injected medicine, called dupilumab, that is also approved for AD. WHAT WERE THE RESULTS?: The study showed that abrocitinib was more effective than dupilumab in providing itch relief after 2 weeks. In addition, people who were taking abrocitinib for 4 and 16 weeks experienced greater improvement in the visible skin signs of AD than people who were taking dupilumab. The number of people who had health complaints while taking abrocitinib was similar to the number of people who had health complaints while taking dupilumab. Most of these complaints were minor. WHAT DO THE RESULTS MEAN?: Abrocitinib was more effective than dupilumab in quickly improving the signs and symptoms of moderate or severe AD in people who did not show improvement with prescribed medications like creams or ointments. Clinical Trial Registration: NCT04345367 (ClinicalTrials.gov).

The efficacy of medicinal plant preparations in the alleviation of radiodermatitis in patients with breast cancer: A systematic review of clinical trials.

Radiodermatitis in breast cancer patients varies from mild irritation to life-threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty-five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis.

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial.

AIM: Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF. METHOD: Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis. RESULTS: A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes. CONCLUSION: While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.

Effect of Ointment Base on the Skin Wound-Healing Deficits in Streptozotocin-Induced Diabetic Rat.

Wound-healing deficits of the skin, one of the most common complications in patients with diabetes, delay wound healing, significantly reducing the patient's QOL. Therefore, the topical treatment of wound areas with drug-containing ointments and dressings is important. In this study, we investigated the effect of various ointment bases on skin wound healing in normal and streptozotocin-induced diabetic rats (STZ rats). Three ointment bases were used: white ointment (oil-based), absorbent cream (emulsion-based, w/o), and macrogol ointment (water-based). Skin wound healing in STZ rats was delayed compared with that in normal rats. Each of the three ointment bases was applied to the skin wound area in normal rats, and there was no difference in the therapeutic effect. The therapeutic effect of both white ointment and absorbent cream was higher in the STZ rats group than that in the non-treated group, and delayed wound healing was observed in STZ rats treated with macrogol ointment. In conclusion, skin wound healing in STZ rats is affected by the properties of the ointment base, and it is important to use an ointment base that controls the drying of the wound area in STZ rats. These findings provide information for the selection of ointment bases useful for application to skin wounds in patients with diabetes.