Effect Of Topical Therapy Research Articles

Long-Term Efficacy and Tolerability of an Emollient Containing Glycerol and Paraffin for Moderate-to-Severe Uremic Xerosis: A Randomized Phase3 Study.

There is an unmet need for effective topical therapies for patients with uremic xerosis and chronic kidney disease-associated pruritus (CKD-aP). The long-term efficacy and tolerability of an emollient containing glycerol 15% and paraffin 10% (V0034CR) was evaluated in a phase3 study. In this randomized, double-blind, two-parallel group, vehicle-controlled study, patients with moderate-to-severe uremic xerosis were randomized to once-daily application of V0034CR or vehicle control for 28days (periodI). This was followed by a treatment-free period of ≤ 21days (periodII), then all patients received open-label treatment with V0034CR for ≥ 84days (periodIII). Outcomes included treatment response at the end of periodI (El Gammal's xerosis severity score), instrumental measures of scaling (D-Squame technique), time to relapse during periodII, rate of recurrence during periodIII, pruritus severity over time, patient acceptability, and adverse events (AEs). The intent-to-treat population comprised 235 patients randomized to V0034CR (n = 118) or vehicle control (n = 117) during periodI. Treatment response at the end of periodI was achieved by 71 patients (60.2%) in the V0034CR group versus 48 (41.0%) with vehicle control (p = 0.0041). This coincided with greater reductions in the total surface area of squames (p = 0.001 vs vehicle control). Xerosis relapsed progressively without treatment in periodII; however, remission was durable under maintenance therapy in periodIII. Improvements in pruritus severity were comparable between V0034CR and vehicle control, suggesting that the antipruritic effect of V0034CR was mainly exerted by its oil-in-water emulsion base. V0034CR had high patient acceptability and was well tolerated; the most common treatment-related AEs were irritation or erythema (2.1%), exacerbated pruritus (1.3%), and vesicles at the application site (0.9%). These data support the use of V0034CR, with its hydrating and occlusive properties, for the long-term management of patients with moderate-to-severe uremic xerosis and CKD-aP. ClinicalTrials.gov identifier NCT01084148; EudraCT number 2006-002201-31.

Fighting A New Front On An Old Battlefield: Examining the Development of Topical Antimicrobial Care to Control Burn Wound Sepsis.

Recognition of invasive burn wound sepsis as a major cause of morbidity and mortality in burn injured patients has profoundly changed the management of burn wounds and its associated complications. The development of effective topical antimicrobial therapy is one of the last major developments of modern burn care and has been driven by major world events and scientific breakthroughs. Topical antimicrobial burn care has evolved from the use of anecdotal remedies to scientific breakthroughs such as Moyer's successful dilution of silver nitrate solution, Fox's described benefit of silver sulfadiazine use in animal models, and Pruitt's dramatic improvement in post-burn mortality using topical mafenide acetate in burn wounds. The objective of this manuscript is to review the definition of burn wound sepsis and highlight the major developments and breakthroughs in topical burn wound care throughout history. This includes historical events like major wars or domestic fires that have influenced or impacted the understanding and treatment of burn wounds. Newer advances in topical antimicrobial care such as nanosilvers and dressing technologies that improve the morbidity and mortality associated with burn wound sepsis and novel approaches to management will also be discussed. To improve burn care, it is prudent to look to the past and learn from the experiences of those who contributed to the control of burn wound sepsis.

Multifunctional polymeric nanocapsules with enhanced cartilage penetration and retention for osteoarthritis treatment

Osteoarthritis (OA) is a prevalent joint disease characterized by cartilage degeneration and subchondral bone homeostasis imbalance. Effective topical OA therapy is challenging, as therapeutic drugs often suffer from insufficient penetration and rapid clearance. We develop miniature polydopamine (PDA) nanocapsules (sub-60 nm), which are conjugated with collagen-binding polypeptide (CBP) and loaded with an anabolic drug (i.e., parathyroid hormone 1–34, PTH 1–34) for efficient OA treatment. Such multifunctional polymeric nanocapsules, denoted as PDA@CBP-PTH, possess deformability when interacting with the dense collagen fiber networks, enabling the efficient penetration into 1 mm cartilage in 4 h and prolonged retention within the joints up to 28 days. Moreover, PDA@CBP-PTH nanocapsules exhibit excellent reactive oxygen species scavenging property in chondrocytes and enhance the anabolism in subchondral bone. The nanosystem, as dual-mode treatment for OA, demonstrates rapid penetration, long-lasting effects, and combinational therapeutic impact, paving the way for reversing the progression of OA for joint health care.

Efficacy and Safety of Topical Roflumilast for the Treatment of Psoriasis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Plaque psoriasis is commonly treated topically with glucocorticoids and vitamin D derivatives. However, potential side effects such as skin atrophy underscore the need for safe and effective alternative topical therapies. Recently, the US Food and Drug Administration (FDA) and Health Canada approved roflumilast 0.3% cream as an option for treating this disease. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of topical roflumilast 0.3% compared with vehicle for plaque psoriasis. PubMed, Embase, ClinicalTrials.gov, and Cochrane databases were searched from inception to 1 May 2024, assessing the outcomes of Investigator's Global Assessment (IGA) or body-IGA success (clear or almost clear status plus an at least 2-grade improvement from baseline), Psoriasis Area and Severity Index (PASI)-50, PASI-75, PASI-90, intertriginous-IGA success (clear or almost clear status on the intertriginous-IGA plus an at least 2-grade improvement from baseline), and adverse events (AEs). Statistical analysis was performed using Review Manager, R software, and RStudio. Heterogeneity was determined using the Cochran Q test and I2 statistics. Four RCTs were included, comprising a total of 1403 patients, of whom 885 (63.1%) received topical roflumilast 0.3% and 518 (36.9%) received vehicle. At week 8, the achievement of IGA or body-IGA success was significantly higher among those treated with topical roflumilast than in the vehicle group [relative risk (RR) 5.07; 95% confidence interval (CI) 3.55-7.23; p < 0.01]. Similar findings were observed at week 8 for PASI-50 (RR 2.73; 95% CI 2.27-3.29; p < 0.01), PASI-75 (RR 4.48; 95% CI 2.26-8.89; p < 0.01), and PASI-90 (RR 5.61; 95% CI 2.57-12.25; p < 0.01). Corresponding outcomes were found at weeks 2, 4, and 6. Additionally, a higher percentage of patients treated with topical roflumilast 0.3% once daily achieved intertriginous-IGA success, compared with those receiving vehicle, at week 8 (71.9% versus 20.5%; RR 3.32; 95% CI 2.11-5.22; p < 0.01), with similar findings at weeks 2, 4, and 6. While a significant difference was observed in the overall incidence of AEs between the topical roflumilast and vehicle groups, there was no difference in treatment-related AEs, serious AEs, or AEs leading to study discontinuation. These findings support the superiority of topical roflumilast 0.3% over vehicle and suggest its use as a valuable asset for the treatment of plaque psoriasis. International Prospective Register of Systematic Reviews (PROSPERO), CRD42023456494.

Histopathological and Immunological Effects of Nebivolol 5% Topical Cream in Mice Model of Imiquimod-Induced Psoriasis

Background: Psoriasis is a chronic inflammatory skin condition that affects multiple systems. Topical therapy is one of the most important modalities in the treatment of this disease, and efforts are directed toward developing more effective topical therapies. Objective: To investigate the possible anti-psoriatic effect of Nebivolol 5% topical cream in mice based on observational, histopathological, and biochemical outcomes. Methods: Forty-five male Swiss Albino mice were divided into five groups; each group contained nine mice with shaved dorsal skin. Group I remained as the control group while the rest of the groups were induced psoriasis by Imiquimod (IMQ) for six consecutive days and underwent different interventions for each group for eight consecutive days, including administering Nebivolol 5% topical cream. The clinical, pathological and laboratory effects were then measured. Results: Topical nebivolol significantly reduced the inflammatory signs of the psoriatic lesions, and these findings were supported by the histopathological examination. Topical Nebivolol also significantly decreased IL-17 levels, as well as Tumor Necrosis Factor-alpha (TNF-α) levels and Vascular Endothelial Growth Factor (VEGF) levels, in comparison with the non-treated Imiquimod-induced psoriatic mice group. Conclusions: Nebivolol has a comparable anti-psoriatic effect to the effect of clobetasol due to its anti-inflammatory and antioxidant effects. It could be a promising future treatment for psoriasis as an alternative to steroids.

Current aspects of the treatment of acute tonsillopharyngitis: the place of topical therapy

The problem of acute tonsillopharyngitis remains relevant despite a huge amount of research. According to modern clinical guidelines, practically the only indication for prescribing systemic antibacterial therapy remains the GAS etiology of acute tonsillopharyngitis. At the same time, in clinical practice there are often cases of patients independently and unjustifiably starting to take systemic antibacterial drugs due to severe pain, which they were unable to relieve with the use of topical drugs. Most cases of acute tonsillopharyngitis are of a viral etiology. According to the modern guidelines, there is almost the one and only indication for antibiotics in patients with acute tonsillitis. Taking into account, the timing of a standard microbiological study, special clinical scales are used to quickly assess the clinical picture, according to which the patient scores a certain number of points depending on whether certain criteria are met. The most widely used is the McIsaac scale, which takes into account, in addition to the clinical picture, the patient’s age. At the same time, in clinical practice there are often cases of patients independently and unjustifiably starting to take systemic antibacterial drugs due to severe pain, which they were unable to relieve with the use of topical drugs. Thus, timely prescription of topical drugs effective for pain relief occupies an important place in the management of patients with both viral and bacterial acute tonsillopharyngitis. The article presents a series of clinical cases of acute tonsillopharyngitis, which can be characterized by the complexity of differential diagnosis. Using their own observations as an example, the authors demonstrate the importance of timely effective topical therapy, in particular with the antiseptic drug Mitraseptin-PRO (benzyldimethylmyristoylaminopropylammonium).

Ocular surface involvement and histopathologic changes in the acute stage of Stevens-Johnson syndrome and toxic epidermal necrolysis: a cross-sectional study

BackgroundStevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and extremely serious drug-induced dermatological disorders. The ocular surface condition at the early stage has been little studied and should contribute to novel perspectives in early and effective topical therapy of these diseases. The objectives of the study were to evaluate the acute phase of ocular surface involvement and histopathologic changes in patients with acute SJS/TEN.MethodsTen patients with acute phase of SJS/TEN onset and eleven age- and sex-matched healthy volunteers were recruited. Ocular surface symptoms and signs, conjunctival impression cytology, and tear multi-cytokine were assessed.ResultsOcular surface objective signs were normal at the acute stage of SJS/TEN, while most patients have abnormal ocular surface subjective symptoms and meibomian gland secretion. Conjunctival impression cytology showed a significant decrease in goblet cell density and severe ocular surface squamous metaplasia in acute SJS/TEN patients. Tear multi-cytokine analysis showed all 21 pro- and anti-inflammatory cytokines all sharply elevated. Goblet cell density was significantly negatively correlated with tear C-X3-C motif chemokine ligand 1 (CX3CL1) and interleukin 13.ConclusionsSevere pathologic squamous metaplasia and inflammation onset in the ocular surface at the acute stage of the SJS/TEN, even if the ocular surface condition seemed basically normal with adequate systemic immunosuppressant and general supportive treatment. Early topical anti-inflammatory therapy should be carried out actively.

Topical selective TYK2 inhibition attenuates inflammation and clinical symptoms in a mouse model of human psoriasis

Abstract Psoriasis is a chronic skin condition, that affects ~8M patients in the United States. A majority (~7M) of patients suffer from mild to moderate form of disease that lacks safe &amp; effective treatment options. Although antibodies targeting Th1/Th17 cytokines (eg IL12/IL23/IL17) are highly effective in moderate to severe psoriasis, they are not prescribed to mild to moderate patients due to high costs &amp; safety concerns. There is a huge unmet need for developing safe and effective non-steroidal topical therapies. Small molecule inhibitors of Th1/Th17 pathways with optimal topical drug like properties can effectively address patient needs; making TYK2 inhibitors (TYK2i) attractive candidates for treating mild to moderate psoriasis. However, given the high degree of structural similarity among JAK family, designing topical selective TYK2i have remained a challenge. Using an innovative structure based approach, we have designed, synthesized and characterized TYK2i optimized for topical drug like properties and JAK family selectivity using free energy perturbation (FEP) methods and medchem SAR. We have identified TYK2i with pM to low nM potencies that are highly selective for TYK2 among 468 kinases. These analogs have enhanced topical bioavailability with suitable drug like properties. In a mouse model of psoriasis, these analogs dose-dependently suppressed PASI clinical scores, ear &amp; back skin thickness and inflammation. Additionally, skin histology showed significant attenuation of epidermal thickening and pSTAT activation suggesting that topical TYK2 inhibition retains anti-inflammatory activity while eliminating potential for dose-limiting side effects observed with systemic non-selective TYK2 or other JAK inhibitors. This research has been fully funded by Alembic Pharmaceuticals Ltd., including salary support to all authors.

Design and evaluation of nanosized griseofulvin loaded bio-adhesive layers of acacia catechu (Katha) bio-penetrant for Transungual delivery

Topical therapy is highly desirable in treating nail disorders due to its localized effects, which results in minimal adverse systemic events and possibly improved adherence. However, the effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Infections of foot and hand nails by fungi are a very common condition in millions of people. They account for about half of all nail disorders and are estimated to occur in over 10% of the population. Griseofulvin is an antifungal medication which acts by restraining microtubules and blocking contagious mitosis, consequently a fungistatic. Orally griseofulvin has a long elimination half-life (9-21 hrs), highly variable bioavailability (25to70%), Hepatic demethylation and glucuronidation metabolism and frequent doses(500 to 1000mg) for adult and (11mg) for children. Katha(catechu) is an imperative restorative plant utilized as a part of Ayurveda for such a variety of sicknesses and generally for mother healthcare. Solvent casting technique was used to prepare the bio-adhesive layers. Nine formulations were prepared by using griseofulvin(drug), acacia catechu as bio-penetrant, beetroot as bio-polymer and fructose as film ability. The bio-adhesive layers were physically examined for color and evaluated for thickness, weight uniformity test, folding endurance, Spectral studies, stability studies, in-vitro & ex-vivo studies.

Investigation on Utility of Some Novel Terpenes on Transungual Delivery of Terbinafine for the Management of Onychomycosis.

Onychomycosis is a fungal disorder of the nail which afflicts 5% of the population worldwide. The disease is strenuous to cure as it is chronic, hard to eliminate and tends to recur. Topical therapy is at the forefront for the treatment of many disorders of nail. However, the success rate of topical therapy has been halted owing to the poor permeation of topical therapeutics across densely keratinized nail barrier. Therefore, ungual drug permeation must be improved for an effective topical therapy. An approach to achieve this goal would be the use of terpenes from natural sources as potential penetration enhancers. This study is aimed to explore the effectiveness of some novel terpenes as potential penetration enhancers on transungual delivery of terbinafine. Ex-vivo permeation studies were performed by sopping the nail clippings of healthy human volunteers in control and working solutions containing terbinafine (5mg/ml) per se and terbinafine (5mg/ml) with 6% of each terpenes including lavandulol, safranal, rose oxide, limonene, 3-methyl-2-butene-1-ol, and linalool respectively for 48 hours. The terbinafine concentration in nail samples was determined using a HPLC (High Performance Liquid Chromatography method. Statistical analysis showed that studied terpenes increase transungual penetration of terbinafine in the following order: linalool > rose oxide > 3-methyl-2-butene-1-ol > safranal > limonene > lavandulol acetate. Accordingly, linalool was found to be the most effective penetration enhancer for the transungual delivery of terbinafine. It is concluded that linalool can be used as safe and potential penetration enhancer for enhancing the transungual delivery of terbinafine for onychomycosis.

THE EFFECTIVE MANAGEMENT OF SEBACEOUS CYST (KATTI) THROUGH TOPICAL THERAPY VELLAI MEZHUGU IN SIDDHA

Background: Sebaceous cysts are common noncancerous cysts of the skin. Sebaceous cysts are mostly found on face, neck and trunk. They grow slowly and become uncomfortable. Cysts can develop if the gland or its duct becomes damaged or blocked. Small cysts are typically not painful. Large cysts on the face, neck and trunk may cause pain. Among 32 Siddha external therapies, topical therapy is one of the procedures that minimize the risks of systemic side effects and provides intimate contact between the drug and the target tissue. To study and document Aim&amp; objective: the effectiveness of topical therapy through vellai mezhugu application in sebaceous cyst (katti). Methodology:A male case who reported with the complaint of cyst in the OPD of Ayothidass pandithar Hospital was recruited for the study. General physical examination along with local examination was used to diagnose the disease. The procedure was done as per the standard operating procedure. Size and symptoms of the cyst were used as the assessment criteria to monitor the outcome. Results:The symptomatic relief of pain &amp; swelling was well appreciated by the patient after the procedure. The patient had good prognosis with each visit and recurrence of cyst was not reported till 6 months of follow-up. Conclusion:From this study, Vellai Mezhugu application on seboceous cyst offers the satisfactory result.

33460 Roflumilast foam 0.3% treatment of seborrheic dermatitis is effective and safe and improves patient quality of life: Results from a phase 2 study

Seborrheic dermatitis is a chronic inflammatory skin condition that may cause discomfort, itching, and reduced quality of life. No novel treatments have been developed in decades. A phase 2, 8-week study investigated once-daily roflumilast foam 0.3%, a selective and highly potent phosphodiesterase-4 inhibitor, in patients with seborrheic dermatitis. Adult patients with seborrheic dermatitis of at least moderate Investigator Global Assessment (IGA) severity affecting ≤20% of body surface area were randomized to roflumilast foam 0.3% (n = 154) or vehicle (n = 72). For the primary endpoint, significantly more roflumilast-treated patients (73.8%) than vehicle-treated patients (40.9%; P < .0001) achieved an IGA score of clear or almost clear plus 2-grade improvement from baseline at week 8; significant differences occurred as early as the first postbaseline visit (week 2, P = .0033). Patients in the roflumilast foam 0.3% group had greater improvement in health-related quality of life (Scalpdex) scores compared with those in the vehicle group at all postbaseline assessments (P ≤ .0019). At Weeks 4 and 8, roflumilast-treated patients had greater improvement in Dermatology Life Quality Index compared with vehicle-treated patients (P ≤ .0380). Roflumilast also increased the percentage of patients achieving a 4-point response on the worst itch-numeric rating scale at all postbaseline visits (evaluated in patients with baseline score ≥4; P ≤ .0009). Rates of application site pain, treatment-related adverse events, and discontinuations due to adverse events were low and comparable to vehicle. These data indicate investigational once-daily roflumilast foam 0.3% is a promising, novel and effective topical therapy that may rapidly improve quality of life in patients with seborrheic dermatitis.

Possibilities of effective topical therapy in treatment of acute otitis media in children: A review

Acute otitis media (AOM) is a common infection of the middle ear in children with predominant symptoms of pain and hearing impairment. If antibiotics are prescribed, they take time to act on the inflammatory process, so the main focus is on relieving pain. Topical anesthetics have the advantage of having fewer systemic side effects when analgesic is used. The review covers a systematic analysis of the literature on the problem of AOM in children for the period from 1990 to 2021. Analgesic ear drops with lidocaine and phenazone can provide first-line pain relief for otitis media without systemic side effects such as gastrointestinal disorders and nausea and can maintain a wait-and-see attitude towards saving antibiotics. A combined drug containing a combination of the anesthetic lidocaine and the anti-inflammatory drug phenazone shows optimal action to eliminate pain and inflammation in children with AOM. The drug, which is recommended from the birth of a child and included in the National clinical guidelines for the treatment of AOM (2021), can be prescribed by a pediatrician and a general and family practitioner.

Treatment of Scalp Psoriasis.

Scalp involvement is seen in a majority of individuals with psoriasis, a chronic autoimmune skin disease with variable phenotypes. Occasionally, isolated scalp involvement is observed; and this causes significant psychosocial morbidity. Management of scalp psoriasis is difficult, in part due to the difficulty of applying topical agents and its refractory nature. Various treatment options are available with variable efficacy. Topical agents include topical steroids, keratolytics, tar and anthralin compounds, vitamin D analogues, and vitamin A derivatives. The combination treatment of topical betamethasone and calcipotriene is the most effective topical therapy. Systemic agents include conventional agents such as methotrexate, cyclosporine, and oral retinoids. Biologics offer a greater efficacy, with near complete or complete clearance of the scalp. In this article we review the published literature on adult and scalp psoriasis to highlight its treatment. Articles published in peer-reviewed journals were included for qualitative analysis of the literature, including reviews, clinical trials, case series, case reports published in the electronic database (MEDLINE/PubMed) through June 2021, cross references of respective articles, and trials from clinicaltrials.gov. J Drugs Dermatol. 2022;21(8):833-837. doi:10.36849/JDD.6498.

The Efficacy of Azelaic Acid 20% Cream in the Treatment of Scalp Alopecia Areata

Introduction: Alopecia areata is a common, inflammatory, non-scarring type of hair loss that affects persons of both sexes and all age groups, with prevalence in the general population of approximately 0.1–0.2%. It is characterized by variable clinical presentations, ranging from single or multiple well-circumscribed patches of hair loss to extensive involvement with complete absence of body and scalp hair. Alopecia areata is an autoimmune disease of the hair follicle. Its pathogenesis is associated with loss of follicular immune privilege and T-cell mediated inflammatory response, leading to interruption of the hair growth cycle. The diagnosis of alopecia areata is usually based on clinical manifestations in addition to using severity of alopecia tool score. Currently, there is no treatment for alopecia areata approved by the US Food and Drugs Administration. However, several treatment modalities for alopecia areata have been introduced with variable outcomes. Although topical and systemic immunomodulators are the mainstay options, there is still a lack of high-quality randomized controlled trials supporting these treatment modalities. Topical Corticosteroids are considered the first-line therapy for patch-type alopecia areata. Azelaic acid is a dicarboxylic acid, derived from the fungus Pityrosporum ovale and is regarded as an effective topical therapy for patchy alopecia areata. Aim of study: The present study aims to measure the efficacy of topical azelaic acid cream 20% in the treatment of alopecia areata. Patients and Methods: The all 30 patients were collected from Erbil Dermatology Teaching Center. They were divided into two groups: group A includes fifteen patients on topical clobetasol propionate 0.05% cream; group B includes fifteen patients on topical azelaic acid 20% cream. Both treatment groups were followed up for period of around twelve weeks with monthly check up visits. Both drugs were applied topically once daily at night. Results: the comparison between the baseline and 12 weeks visits for each study group concerning severity of alopecia tool score shows that the mean of the score for both groups at 12 weeks visit is lower than that of baseline visit in a statistically significant way (group A, p=0.007, group B, p=0.036). Conclusions: This study showed that topical azelaic acid cream 20% has an acceptable efficacy in comparison to topical clobetasol ointment 0.05% in the treatment of localized alopecia areata of scalp and can be considered as a therapeutic option for this condition.

Real-world treatment outcomes with halobetasol propionate 0.01%/tazarotene 0.045% lotion in patients with mild-to-moderate plaque psoriasis: A Canadian multicenter retrospective chart review

To the Editor: Halobetasol propionate 0.01%/tazarotene 0.045% lotion (HP/TAZ) was developed as an effective, safe, and tolerable topical therapy for plaque psoriasis. It has been investigated in moderate-to-severe plaque psoriasis1-3; however, real-world data on the use of topical fixed-combination therapies for plaque psoriasis, particularly milder disease courses, are limited.

The Unfulfilled Promise of Inhaled Therapy in Ventilator-Associated Infections: Where Do We Go from Here?

Respiratory infection is common in intubated/tracheotomized patients and systemic antibiotic therapy is often unrewarding. In 1967, the difficulty in treating Gram-negative respiratory infections led to the use of inhaled gentamicin, targeting therapy directly to the lungs. Fifty-three years later, the effects of topical therapy in the intubated patient remain undefined. Clinical failures with intravenous antibiotics persist and instrumented patients are now infected by many more multidrug-resistant Gram-negative species as well as methicillin-resistant Staphylococcus aureus. Multiple systematic reviews and meta-analyses suggest that there may be a role for inhaled delivery but “more research is needed.” Yet there is still no Food and Drug Administration (FDA) approved inhaled antibiotic for the treatment of ventilator-associated infection, the hallmark of which is the foreign body in the upper airway. Current pulmonary and infectious disease guidelines suggest using aerosols only in the setting of Gram-negative infections that are resistant to all systemic antibiotics or not to use them at all. Recently two seemingly well-designed large randomized placebo-controlled Phase 2 and Phase 3 clinical trials of adjunctive inhaled therapy for the treatment of ventilator-associated pneumonia failed to show more rapid resolution of pneumonia symptoms or effect on mortality. Despite evolving technology of delivery devices and more detailed understanding of the factors affecting delivery, treatment effects were no better than placebo. What is wrong with our approach to ventilator- associated infection? Is there a message from the large meta-analyses and these two large recent multisite trials? This review will suggest why current therapies are unpredictable and have not fulfilled the promise of better outcomes. Data suggest that future studies of inhaled therapy, in the milieu of worsening bacterial resistance, require new approaches with completely different indications and endpoints to determine whether inhaled therapy indeed has an important role in the treatment of ventilated patients.

25406 Comparison of biologic initiation and health care costs among patients with psoriasis receiving fixed-dose combination halobetasol-propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion vs calcipotriene 0.005%/ betamethasone dipropionate 0.064% (CAL/BD) foam

Background: Patients with psoriasis may benefit from more tolerable and effective topical therapy options with the potential to delay or prevent biologic initiation.

Transdermal Permeation of Caffeine Aided by Ionic Liquids: Potential for Enhanced Treatment of Cellulitis.

Ginoid hydrolipodystrophy (HDLG) or "cellulite" involves alteration of the cutaneous relief and occurs in 80-90% of the female population. Several topical treatments are available with the use of substances capable of stimulating lipolysis, such as caffeine. However, the effectiveness of topical therapy is related to the processes of release and permeation of the active in skin cells. In this sense, ionic liquids, such as choline geranate, are considered to facilitate topical permeation agents. In this way, the aim of this research was to develop and evaluation of the effectiveness of a cosmetic product for topical treatment of cellulite with caffeine in association with choline geranate. The choline geranate was synthesized by the reaction between geranic acid and choline hydroxide [1: 2]. The gel was prepared using 2% Carpobol 940®, 5% caffeine, and 1% choline geranate. Preliminary and accelerated stability tests were performed by checking pH, spreadability, and organoleptic characteristics. The transdermal permeation capacity of caffeine in vitro was evaluated by the Franz cell permeation assay, and the gel cytotoxicity by the MTS method. To prove the efficacy in the treatment of cellulite, a pilot type 1 clinical trial was carried out. The formulation was considered stable and the product maintained your characteristics during 180 days of storage. The product showed moderate cytotoxicity and high skin permeation capacity. In the clinical trial, it showed results superior to the caffeine gel without ionic liquid. The developed gel favored the cutaneous permeation of caffeine, showing a promising product in the treatment of cellulite.

Оценка эффективности и безопасности местного средства на основе аммония глицирризината при ветряной оспе у детей

The search for new effective and safe medications for external therapy of varicella in children remains highly relevant. Objective. To evaluate the efficacy and safety of a topical gel containing ammonium glycyrrhizinate for the treatment of varicella in children. Patients and methods. This study included 32 patients with varicella aged between 4 and 9 years. Study participants were randomized into two groups: patients in the experimental group received topical therapy with ammonium glycyrrhizinate, whereas patients in the control group received topical therapy with a medicine containing calamine and zinc oxide. Results. Patients in the experimental group demonstrated faster recovery than in control group: they had shorter period of new rash, shorter duration of rash on the mucous membranes; on day 4, there was a significant decrease in the proportion of patients with local edema and hyperemia in the area of rash; there was also a reduction in itching during the entire observation period, while patients in the control group had worsening of itching on days 5 and 6; we observed a 2-day reduction in the duration of secondary bacterial infection of rash. In the experimental group, there was a decrease in the proportion of patients with fatigue and its duration (to 4 days), as well as faster restoration of appetite compared to control group. Conclusion. Our findings allow us to recommend the gel containing ammonium glycyrrhizinate for effective topical therapy of varicella in children. Key words: ammonium glycyrrhizinate, varicella, glycyrrhizic acid, children, topical therapy